Defining mtDNA origins and population stratification in Rio de Janeiro.

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Simão, Filipa; Ferreira, Ana Paula; de Carvalho, Elizeu Fagundes; Parson, Walther; Gusmão, Leonor

2018-05-01

The genetic composition of the Brazilian population was shaped by interethnic admixture between autochthonous Native Americans, Europeans settlers and African slaves. This structure, characteristic of most American populations, implies the need for large population forensic databases to capture the high diversity that is usually associated with admixed populations. In the present work, we sequenced the control region of mitochondrial DNA from 205 non-related individuals living in the Rio de Janeiro metropolitan region. Overall high haplotype diversity (0.9994 ± 0.0006) was observed, and pairwise comparisons showed a high proportion of haplotype pairs with more than one-point differences. When ignoring homopolymeric tracts, pairwise comparisons showed no differences 0.18% of the time, and differences in a single position were found with a frequency of 0.32%. A high percentage of African mtDNA was found (42%), with lineages showing a major South West origin. For the West Eurasian and Native American haplogroups (representing 32% and 26%, respectively) it was not possible to evaluate a clear geographic or linguistic affiliation. When grouping the mtDNA lineages according to their continental origin (Native American, European and African), differences were observed for the ancestry proportions estimated with autosomal ancestry-informative markers, suggesting some level of genetic substructure. The results from this study are in accordance with historical data where admixture processes are confirmed with a strong maternal contribution of African maternal ancestry and a relevant contribution of Native American maternal ancestry. Moreover, the evidence for some degree of association between mtDNA and autosomal information should be considered when combining these types of markers in forensic analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Genetic characterization of uniparental lineages in populations from Southwest Iberia with past malaria endemicity

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Pereira, Vania; Gomes, Verónica; Amorim, António

2010-01-01

then compared with data from other Portuguese and non-Portuguese populations. In Coruche, the genetic profile was similar to the profile usually found in Portugal. In Alcacer do Sal, the frequency of sub-Saharan mtDNA L lineages was the highest ever reported (22%) in Europe. In Pias, mtDNA diversity revealed...... influence might be traced to ancient contacts with Greeks, Phoenicians, and Carthaginians, who established important trading networks in southern Iberia....

Ancient mtDNA genetic variants modulate mtDNA transcription and replication.

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Sarit Suissa

2009-05-01

Full Text Available Although the functional consequences of mitochondrial DNA (mtDNA genetic backgrounds (haplotypes, haplogroups have been demonstrated by both disease association studies and cell culture experiments, it is not clear which of the mutations within the haplogroup carry functional implications and which are "evolutionary silent hitchhikers". We set forth to study the functionality of haplogroup-defining mutations within the mtDNA transcription/replication regulatory region by in vitro transcription, hypothesizing that haplogroup-defining mutations occurring within regulatory motifs of mtDNA could affect these processes. We thus screened >2500 complete human mtDNAs representing all major populations worldwide for natural variation in experimentally established protein binding sites and regulatory regions comprising a total of 241 bp in each mtDNA. Our screen revealed 77/241 sites showing point mutations that could be divided into non-fixed (57/77, 74% and haplogroup/sub-haplogroup-defining changes (i.e., population fixed changes, 20/77, 26%. The variant defining Caucasian haplogroup J (C295T increased the binding of TFAM (Electro Mobility Shift Assay and the capacity of in vitro L-strand transcription, especially of a shorter transcript that maps immediately upstream of conserved sequence block 1 (CSB1, a region associated with RNA priming of mtDNA replication. Consistent with this finding, cybrids (i.e., cells sharing the same nuclear genetic background but differing in their mtDNA backgrounds harboring haplogroup J mtDNA had a >2 fold increase in mtDNA copy number, as compared to cybrids containing haplogroup H, with no apparent differences in steady state levels of mtDNA-encoded transcripts. Hence, a haplogroup J regulatory region mutation affects mtDNA replication or stability, which may partially account for the phenotypic impact of this haplogroup. Our analysis thus demonstrates, for the first time, the functional impact of particular mtDNA

Multiplexed SNP Typing of Ancient DNA Clarifies the Origin of Andaman mtDNA Haplogroups amongst South Asian Tribal Populations

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Endicott, Phillip; Metspalu, Mait; Stringer, Chris; Macaulay, Vincent; Cooper, Alan; Sanchez, Juan J.

2006-01-01

The issue of errors in genetic data sets is of growing concern, particularly in population genetics where whole genome mtDNA sequence data is coming under increased scrutiny. Multiplexed PCR reactions, combined with SNP typing, are currently under-exploited in this context, but have the potential to genotype whole populations rapidly and accurately, significantly reducing the amount of errors appearing in published data sets. To show the sensitivity of this technique for screening mtDNA genomic sequence data, 20 historic samples of the enigmatic Andaman Islanders and 12 modern samples from three Indian tribal populations (Chenchu, Lambadi and Lodha) were genotyped for 20 coding region sites after provisional haplogroup assignment with control region sequences. The genotype data from the historic samples significantly revise the topologies for the Andaman M31 and M32 mtDNA lineages by rectifying conflicts in published data sets. The new Indian data extend the distribution of the M31a lineage to South Asia, challenging previous interpretations of mtDNA phylogeography. This genetic connection between the ancestors of the Andamanese and South Asian tribal groups ∼30 kya has important implications for the debate concerning migration routes and settlement patterns of humans leaving Africa during the late Pleistocene, and indicates the need for more detailed genotyping strategies. The methodology serves as a low-cost, high-throughput model for the production and authentication of data from modern or ancient DNA, and demonstrates the value of museum collections as important records of human genetic diversity. PMID:17218991

Forensic and phylogeographic characterisation of mtDNA lineages from Somalia.

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Mikkelsen, Martin; Fendt, Liane; Röck, Alexander W; Zimmermann, Bettina; Rockenbauer, Eszter; Hansen, Anders J; Parson, Walther; Morling, Niels

2012-07-01

The African mitochondrial (mt) phylogeny is coarsely resolved but the majority of population data generated so far is limited to the analysis of the first hypervariable segment (HVS-1) of the control region (CR). Therefore, this study aimed on the investigation of the entire CR of 190 unrelated Somali individuals to enrich the severely underrepresented African mtDNA pool. The majority (60.5 %) of the haplotypes were of sub-Saharan origin with L0a1d, L2a1h and L3f being the most frequently observed haplogroups. This is in sharp contrast to previous data reported from the Y-chromosome, where only about 5 % of the observed haplogroups were of sub-Saharan provenance. We compared the genetic distances based on population pairwise F (st) values between 11 published East, Central and North African as well as western Asian populations and the Somali sequences and displayed them in a multi-dimensional scaling plot. Genetic proximity evidenced by clustering roughly reflected the relative geographic location of the populations. The sequences will be included in the EMPOP database ( www.empop.org ) under accession number EMP00397 upon publication (Parson and Dür Forensic Sci Int Genet 1:88-92, 2007).

Complete mtDNA genomes of Filipino ethnolinguistic groups: a melting pot of recent and ancient lineages in the Asia-Pacific region

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Delfin, Frederick; Min-Shan Ko, Albert; Li, Mingkun; Gunnarsdóttir, Ellen D; Tabbada, Kristina A; Salvador, Jazelyn M; Calacal, Gayvelline C; Sagum, Minerva S; Datar, Francisco A; Padilla, Sabino G; De Ungria, Maria Corazon A; Stoneking, Mark

2014-01-01

The Philippines is a strategic point in the Asia-Pacific region for the study of human diversity, history and origins, as it is a cross-road for human migrations and consequently exhibits enormous ethnolinguistic diversity. Following on a previous in-depth study of Y-chromosome variation, here we provide new insights into the maternal genetic history of Filipino ethnolinguistic groups by surveying complete mitochondrial DNA (mtDNA) genomes from a total of 14 groups (11 groups in this study and 3 groups previously published) including previously published mtDNA hypervariable segment (HVS) data from Filipino regional center groups. Comparison of HVS data indicate genetic differences between ethnolinguistic and regional center groups. The complete mtDNA genomes of 14 ethnolinguistic groups reveal genetic aspects consistent with the Y-chromosome, namely: diversity and heterogeneity of groups, no support for a simple dichotomy between Negrito and non-Negrito groups, and different genetic affinities with Asia-Pacific groups that are both ancient and recent. Although some mtDNA haplogroups can be associated with the Austronesian expansion, there are others that associate with South Asia, Near Oceania and Australia that are consistent with a southern migration route for ethnolinguistic group ancestors into the Asia-Pacific, with a timeline that overlaps with the initial colonization of the Asia-Pacific region, the initial colonization of the Philippines and a possible separate post-colonization migration into the Philippine archipelago. PMID:23756438

MtDNA diversity and genetic lineages of four cattle breeds in Malaysia

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Somarny, W.W.M.Z.

2015-06-01

Full Text Available There is lack of comprehensive studies on the genetic diversity or phylogenetic analysis of beef cattle breeds in Malaysia. In this study, the partial sequence of mitochondrial DNA cytochrome b gene (cyt b was analysed from blood samples obtained from 25 Chinese Yellow Cattle (CY, 33 Kedah-Kelantan (KK, 32 Brakmas (BM and 30 Bali cattle (BC. Based on these 120 individuals, 19 mtDNA haplotypes (GenBank Accession No. GU67340 - GU67358 were identified by polymorphisms at 31 sites. Hap19 was predominant in BM (78%, KK (82% and CY (100% indicating similar origin or gene flow between breeds whilst Hap11 was exclusively for BC. However, there were only two nucleotide differences between these two major haplotypes. These results can be interpreted that these representative cattle in these haplotypes are admixtures of B. indicus or B. javanicus through maternal ancestry. Conversely, the CY cattle investigated are highly inbred where no variation could be observed in the short segment investigated.

Understanding influences of culture and history on mtDNA variation and population structure in three populations from Assam, Northeast India.

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Rej, Peter H; Deka, Ranjan; Norton, Heather L

2017-05-06

Positioned at the nexus of India, China, and Southeast Asia, Northeast India is presumed to have served as a channel for land-based human migration since the Upper Pleistocene. Assam is the largest state in the Northeast. We characterized the genetic background of three populations and examined the ways in which their population histories and cultural practices have influenced levels of intrasample and intersample variation. We examined sequence data from the mtDNA hypervariable control region and selected diagnostic mutations from the coding region in 128 individuals from three ethnic groups currently living in Assam: two Scheduled tribes (Sonowal Kachari and Rabha), and the non-Scheduled Tai Ahom. The populations of Assam sampled here express mtDNA lineages indicative of South Asian, Southeast Asian, and East Asian ancestry. We discovered two completely novel haplogroups in Assam that accounted for 6.2% of the lineages in our sample. We also identified a new subhaplogroup of M9a that is prevalent in the Sonowal Kachari of Assam (19.1%), but not present in neighboring Arunachal Pradesh, indicating substantial regional population structuring. Employing a large comparative dataset into a series of multidimensional scaling (MDS) analyses, we saw the Rabha cluster with populations sampled from Yunnan Province, indicating that the historical matrilineality of the Rabha has maintained lineages from Southern China. Assam has undergone multiple colonization events in the time since the initial peopling event, with populations from Southern China and Southeast Asia having the greatest influence on maternal lineages in the region. © 2017 Wiley Periodicals, Inc.

Evolutionary analyses of entire genomes do not support the association of mtDNA mutations with Ras/MAPK pathway syndromes.

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Alberto Gómez-Carballa

Full Text Available BACKGROUND: There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS and related disorders (such as LEOPARD, neurofibromatosis type 1, although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM, which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45, most of them classified as NS patients (n = 42. METHODS/PRINCIPAL FINDINGS: The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg patterns of a typical Iberian dataset (including hgs H, T, J, and U. Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5 are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. CONCLUSIONS/SIGNIFICANCE: As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS.

Evolutionary Analyses of Entire Genomes Do Not Support the Association of mtDNA Mutations with Ras/MAPK Pathway Syndromes

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Cerezo, María; Balboa, Emilia; Heredia, Claudia; Castro-Feijóo, Lidia; Rica, Itxaso; Barreiro, Jesús; Eirís, Jesús; Cabanas, Paloma; Martínez-Soto, Isabel; Fernández-Toral, Joaquín; Castro-Gago, Manuel; Pombo, Manuel; Carracedo, Ángel; Barros, Francisco

2011-01-01

Background There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). Methods/Principal Findings The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. Conclusions/Significance As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS. PMID:21526175

Ecological and genetic divergence between two lineages of Middle American túngara frogs Physalaemus (= Engystomops pustulosus

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Ron Santiago R

2010-05-01

Full Text Available Abstract Background Uncovering how populations of a species differ genetically and ecologically is important for understanding evolutionary processes. Here we combine population genetic methods (microsatellites with phylogenetic information (mtDNA to define genetic population clusters of the wide-spread Neotropical túngara frog (Physalaemus pustulosus. We measure gene flow and migration within and between population clusters and compare genetic diversity between population clusters. By applying ecological niche modeling we determine whether the two most divergent genetic groups of the túngara frog (1 inhabit different habitats, and (2 are separated geographically by unsuitable habitat across a gap in the distribution. Results Most population structure is captured by dividing all sample localities into two allopatric genetic lineages. The Northern genetic lineage (NW Costa Rica is genetically homogenous while the Southern lineage (SW Costa Rica and Panama is sub-divided into three population clusters by both microsatellite and mtDNA analyses. Gene flow is higher within the Northern lineage than within the Southern lineage, perhaps due to increased landscape heterogeneity in the South. Niche modeling reveals differences in suitable habitat between the Northern and Southern lineages: the Northern lineage inhabits dry/pine-oak forests, while the Southern lineage is confined to tropical moist forests. Both lineages seem to have had little movement across the distribution gap, which persisted during the last glacial maximum. The lack of movement was more pronounced for the Southern lineage than for the Northern lineage. Conclusions This study confirms the finding of previous studies that túngara frogs diverged into two allopatric genetic lineages north and south of the gap in the distribution in central Costa Rica several million years ago. The allopatric distribution is attributed to unsuitable habitat and probably other unknown ecological factors

Mitochondrial nucleoid clusters protect newly synthesized mtDNA during Doxorubicin- and Ethidium Bromide-induced mitochondrial stress

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Alán, Lukáš, E-mail: lukas.alan@fgu.cas.cz; Špaček, Tomáš; Pajuelo Reguera, David; Jabůrek, Martin; Ježek, Petr

2016-07-01

Mitochondrial DNA (mtDNA) is compacted in ribonucleoprotein complexes called nucleoids, which can divide or move within the mitochondrial network. Mitochondrial nucleoids are able to aggregate into clusters upon reaction with intercalators such as the mtDNA depletion agent Ethidium Bromide (EB) or anticancer drug Doxorobicin (DXR). However, the exact mechanism of nucleoid clusters formation remains unknown. Resolving these processes may help to elucidate the mechanisms of DXR-induced cardiotoxicity. Therefore, we addressed the role of two key nucleoid proteins; mitochondrial transcription factor A (TFAM) and mitochondrial single-stranded binding protein (mtSSB); in the formation of mitochondrial nucleoid clusters during the action of intercalators. We found that both intercalators cause numerous aberrations due to perturbing their native status. By blocking mtDNA replication, both agents also prevented mtDNA association with TFAM, consequently causing nucleoid aggregation into large nucleoid clusters enriched with TFAM, co-existing with the normal nucleoid population. In the later stages of intercalation (> 48 h), TFAM levels were reduced to 25%. In contrast, mtSSB was released from mtDNA and freely distributed within the mitochondrial network. Nucleoid clusters mostly contained nucleoids with newly replicated mtDNA, however the nucleoid population which was not in replication mode remained outside the clusters. Moreover, the nucleoid clusters were enriched with p53, an anti-oncogenic gatekeeper. We suggest that mitochondrial nucleoid clustering is a mechanism for protecting nucleoids with newly replicated DNA against intercalators mediating genotoxic stress. These results provide new insight into the common mitochondrial response to mtDNA stress and can be implied also on DXR-induced mitochondrial cytotoxicity. - Highlights: • The mechanism for mitochondrial nucleoid clustering is proposed. • DNA intercalators (Doxorubicin or Ethidium Bromide) prevent TFAM

Abundant mtDNA diversity and ancestral admixture in Colombian criollo cattle (Bos taurus).

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Carvajal-Carmona, Luis G; Bermudez, Nelson; Olivera-Angel, Martha; Estrada, Luzardo; Ossa, Jorge; Bedoya, Gabriel; Ruiz-Linares, Andrés

2003-11-01

Various cattle populations in the Americas (known as criollo breeds) have an origin in some of the first livestock introduced to the continent early in the colonial period (16th and 17th centuries). These cattle constitute a potentially important genetic reserve as they are well adapted to local environments and show considerable variation in phenotype. To examine the genetic ancestry and diversity of Colombian criollo we obtained mitochondrial DNA control region sequence information for 110 individuals from seven breeds. Old World haplogroup T3 is the most commonly observed CR lineage in criollo (0.65), in agreement with a mostly European ancestry for these cattle. However, criollo also shows considerable frequencies of haplogroups T2 (0.9) and T1 (0.26), with T1 lineages in criollo being more diverse than those reported for West Africa. The distribution and diversity of Old World lineages suggest some North African ancestry for criollo, probably as a result of the Arab occupation of Iberia prior to the European migration to the New World. The mtDNA diversity of criollo is higher than that reported for European and African cattle and is consistent with a differentiated ancestry for some criollo breeds.

Strong and stable geographic differentiation of swamp buffalo maternal and paternal lineages indicates domestication in the China/Indochina border region.

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Zhang, Yi; Lu, Yongfang; Yindee, Marnoch; Li, Kuan-Yi; Kuo, Hsiao-Yun; Ju, Yu-Ten; Ye, Shaohui; Faruque, Md Omar; Li, Qiang; Wang, Yachun; Cuong, Vu Chi; Pham, Lan Doan; Bouahom, Bounthong; Yang, Bingzhuang; Liang, Xianwei; Cai, Zhihua; Vankan, Dianne; Manatchaiworakul, Wallaya; Kowlim, Nonglid; Duangchantrasiri, Somphot; Wajjwalku, Worawidh; Colenbrander, Ben; Zhang, Yuan; Beerli, Peter; Lenstra, Johannes A; Barker, J Stuart F

2016-04-01

The swamp type of the Asian water buffalo is assumed to have been domesticated by about 4000 years BP, following the introduction of rice cultivation. Previous localizations of the domestication site were based on mitochondrial DNA (mtDNA) variation within China, accounting only for the maternal lineage. We carried out a comprehensive sampling of China, Taiwan, Vietnam, Laos, Thailand, Nepal and Bangladesh and sequenced the mtDNA Cytochrome b gene and control region and the Y-chromosomal ZFY, SRY and DBY sequences. Swamp buffalo has a higher diversity of both maternal and paternal lineages than river buffalo, with also a remarkable contrast between a weak phylogeographic structure of river buffalo and a strong geographic differentiation of swamp buffalo. The highest diversity of the swamp buffalo maternal lineages was found in south China and north Indochina on both banks of the Mekong River, while the highest diversity in paternal lineages was in the China/Indochina border region. We propose that domestication in this region was later followed by introgressive capture of wild cows west of the Mekong. Migration to the north followed the Yangtze valley as well as a more eastern route, but also involved translocations of both cows and bulls over large distances with a minor influence of river buffaloes in recent decades. Bayesian analyses of various migration models also supported domestication in the China/Indochina border region. Coalescence analysis yielded consistent estimates for the expansion of the major swamp buffalo haplogroups with a credibility interval of 900 to 3900 years BP. The spatial differentiation of mtDNA and Y-chromosomal haplotype distributions indicates a lack of gene flow between established populations that is unprecedented in livestock. © 2015 John Wiley & Sons Ltd.

Keeping mtDNA in shape between generations.

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James B Stewart

2014-10-01

Full Text Available Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of this unusual mode of transmission. Many surprising variations in animal mitochondrial biology are known; however, a series of recent studies have identified a core of evolutionarily conserved mechanisms relating to mtDNA inheritance, e.g., mtDNA bottlenecks during germ cell development, selection against specific mtDNA mutation types during maternal transmission, and targeted destruction of sperm mitochondria. In this review, we outline recent literature on the transmission of mtDNA in animals and highlight the implications for human health and ageing.

mtDNA variation predicts population size in humans and reveals a major Southern Asian chapter in human prehistory.

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Atkinson, Quentin D; Gray, Russell D; Drummond, Alexei J

2008-02-01

The relative timing and size of regional human population growth following our expansion from Africa remain unknown. Human mitochondrial DNA (mtDNA) diversity carries a legacy of our population history. Given a set of sequences, we can use coalescent theory to estimate past population size through time and draw inferences about human population history. However, recent work has challenged the validity of using mtDNA diversity to infer species population sizes. Here we use Bayesian coalescent inference methods, together with a global data set of 357 human mtDNA coding-region sequences, to infer human population sizes through time across 8 major geographic regions. Our estimates of relative population sizes show remarkable concordance with the contemporary regional distribution of humans across Africa, Eurasia, and the Americas, indicating that mtDNA diversity is a good predictor of population size in humans. Plots of population size through time show slow growth in sub-Saharan Africa beginning 143-193 kya, followed by a rapid expansion into Eurasia after the emergence of the first non-African mtDNA lineages 50-70 kya. Outside Africa, the earliest and fastest growth is inferred in Southern Asia approximately 52 kya, followed by a succession of growth phases in Northern and Central Asia (approximately 49 kya), Australia (approximately 48 kya), Europe (approximately 42 kya), the Middle East and North Africa (approximately 40 kya), New Guinea (approximately 39 kya), the Americas (approximately 18 kya), and a second expansion in Europe (approximately 10-15 kya). Comparisons of relative regional population sizes through time suggest that between approximately 45 and 20 kya most of humanity lived in Southern Asia. These findings not only support the use of mtDNA data for estimating human population size but also provide a unique picture of human prehistory and demonstrate the importance of Southern Asia to our recent evolutionary past.

Ancient and recent Middle Eastern maternal genetic contribution to North Africa as viewed by mtDNA diversity in Tunisian Arab populations.

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Elkamel, Sarra; Boussetta, Sami; Khodjet-El-Khil, Houssein; Benammar Elgaaied, Amel; Cherni, Lotfi

2018-05-01

Through previous mitochondrial DNA studies, the Middle Eastern maternal genetic contribution to Tunisian populations appears limited. In fact, most of the studied communities were cosmopolitan, or of Berber or Andalusian origin. To provide genetic evidence for the actual contribution of Middle Eastern mtDNA lineages to Tunisia, we focused on two Arab speaking populations from Kairouan and Wesletia known to belong to an Arab genealogical lineage. A total of 114 samples were sequenced for the mtDNA HVS-I and HVS-II regions. Using these data, we evaluated the distribution of Middle Eastern haplogroups in the study populations, constructed interpolation maps, and established phylogenetic networks allowing estimation of the coalescence time for three specific Middle Eastern subclades (R0a, J1b, and T1). Both studied populations displayed North African genetic structure and Middle Eastern lineages with a frequency of 12% and 28.12% in Kairouan and Wesletia, respectively. TMRCA estimates for haplogroups T1a, R0a, and J1b in Tunisian Arabian samples were around 15 000 YBP, 9000 to 5000 YBP, and 960 to 600 YBP, respectively. The Middle Eastern maternal genetic contribution to Tunisian populations, as to other North African populations, occurred mostly in deep prehistory. They were brought in different migration waves during the Upper Paleolithic, probably with the expansion of Iberomaurusian culture, and during Epipaleolithic and Early Neolithic periods, which are concomitant with the Capsian civilization. Middle Eastern lineages also came to Tunisia during the recent Islamic expansion of the 7th CE and the subsequent massive Bedouin migration during the 11th CE. © 2018 Wiley Periodicals, Inc.

Phylogeographical analysis of mtDNA data indicates postglacial expansion from multiple glacial refugia in woodland caribou (Rangifer tarandus caribou.

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Cornelya F C Klütsch

Full Text Available Glacial refugia considerably shaped the phylogeographical structure of species and may influence intra-specific morphological, genetic, and adaptive differentiation. However, the impact of the Quaternary ice ages on the phylogeographical structure of North American temperate mammalian species is not well-studied. Here, we surveyed ~1600 individuals of the widely distributed woodland caribou (Rangifer tarandus caribou using mtDNA control region sequences to investigate if glacial refugia contributed to the phylogeographical structure in this subspecies. Phylogenetic tree reconstruction, a median-joining network, and mismatch distributions supported postglacial expansions of woodland caribou from three glacial refugia dating back to 13544-22005 years. These three lineages consisted almost exclusively of woodland caribou mtDNA haplotypes, indicating that phylogeographical structure was mainly shaped by postglacial expansions. The putative centres of these lineages are geographically separated; indicating disconnected glacial refugia in the Rocky Mountains, east of the Mississippi, and the Appalachian Mountains. This is in congruence with the fossil record that caribou were distributed in these areas during the Pleistocene. Our results suggest that the last glacial maximum substantially shaped the phylogeographical structure of this large mammalian North American species that will be affected by climatic change. Therefore, the presented results will be essential for future conservation planning in woodland caribou.

Data from complete mtDNA sequencing of Tunisian centenarians: testing haplogroup association and the "golden mean" to longevity.

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Costa, Marta D; Cherni, Lotfi; Fernandes, Verónica; Freitas, Fernando; Ammar El Gaaied, Amel Ben; Pereira, Luísa

2009-04-01

Since the mitochondrial theory of ageing was proposed, mitochondrial DNA (mtDNA) diversity has been largely studied in old people, however complete genomes are still rare, being limited to Japanese and UK/US samples. In this work, we evaluated possible longevity associated polymorphisms/haplogroups in an African population, from Tunisia, by performing complete mtDNA sequencing. This population has a mixed Eurasian/sub-Saharan mtDNA gene pool, which could potentially facilitate the evaluation of association for sub-Saharan lineages. Sub-Saharan haplogroups were shown to be significantly less represented in centenarians (9.5%) than in controls (54.5%), but it is not possible to rule out an influence of population structure, which is high in these populations. No recurrent polymorphism were more frequent in centenarians than in controls, and although the Tunisian centenarians presented less synonymous and replacement polymorphisms than controls, this difference was not statistically significant. So far, it does not seem that centenarians have significantly less mildly deleterious substitutions, not only in Tunisia but also in Japanese and UK/US samples, as tested here, not favouring a "golden mean" to longevity.

On the edge of Bantu expansions: mtDNA, Y chromosome and lactase persistence genetic variation in southwestern Angola

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Beleza Sandra

2009-04-01

Full Text Available Abstract Background Current information about the expansion of Bantu-speaking peoples is hampered by the scarcity of genetic data from well identified populations from southern Africa. Here, we fill an important gap in the analysis of the western edge of the Bantu migrations by studying for the first time the patterns of Y-chromosome, mtDNA and lactase persistence genetic variation in four representative groups living around the Namib Desert in southwestern Angola (Ovimbundu, Ganguela, Nyaneka-Nkumbi and Kuvale. We assessed the differentiation between these populations and their levels of admixture with Khoe-San groups, and examined their relationship with other sub-Saharan populations. We further combined our dataset with previously published data on Y-chromosome and mtDNA variation to explore a general isolation with migration model and infer the demographic parameters underlying current genetic diversity in Bantu populations. Results Correspondence analysis, lineage sharing patterns and admixture estimates indicate that the gene pool from southwestern Angola is predominantly derived from West-Central Africa. The pastoralist Herero-speaking Kuvale people were additionally characterized by relatively high frequencies of Y-chromosome (12% and mtDNA (22% Khoe-San lineages, as well as by the presence of the -14010C lactase persistence mutation (6%, which likely originated in non-Bantu pastoralists from East Africa. Inferred demographic parameters show that both male and female populations underwent significant size growth after the split between the western and eastern branches of Bantu expansions occurring 4000 years ago. However, males had lower population sizes and migration rates than females throughout the Bantu dispersals. Conclusion Genetic variation in southwestern Angola essentially results from the encounter of an offshoot of West-Central Africa with autochthonous Khoisan-speaking peoples from the south. Interactions between the Bantus

Regional Differences in the Distribution of the Sub-Saharan, West Eurasian, and South Asian mtDNA Lineages in Yemen

Czech Academy of Sciences Publication Activity Database

Černý, Viktor; Mulligan, C. J.; Rídl, J.; Žaloudková, M.; Edens, C. M.; Hájek, Martin; Pereira, L.

2008-01-01

Roč. 136, č. 2 (2008), s. 128-137 ISSN 0002-9483 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA diversity * regional sampling * population distances * phylogeography Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.353, year: 2008 http://www3.interscience.wiley.com/journal/117899911/abstract

Detailed mtDNA genotypes permit a reassessment of the settlement and population structure of the Andaman Islands.

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Barik, S S; Sahani, R; Prasad, B V R; Endicott, P; Metspalu, M; Sarkar, B N; Bhattacharya, S; Annapoorna, P C H; Sreenath, J; Sun, D; Sanchez, J J; Ho, S Y W; Chandrasekar, A; Rao, V R

2008-05-01

The population genetics of the Indian subcontinent is central to understanding early human prehistory due to its strategic location on the proposed corridor of human movement from Africa to Australia during the late Pleistocene. Previous genetic research using mtDNA has emphasized the relative isolation of the late Pleistocene colonizers, and the physically isolated Andaman Island populations of Island South-East Asia remain the source of claims supporting an early split between the populations that formed the patchy settlement pattern along the coast of the Indian Ocean. Using whole-genome sequencing, combined with multiplexed SNP typing, this study investigates the deep structure of mtDNA haplogroups M31 and M32 in India and the Andaman Islands. The identification of a so far unnoticed rare polymorphism shared between these two lineages suggests that they are actually sister groups within a single haplogroup, M31'32. The enhanced resolution of M31 allows for the inference of a more recent colonization of the Andaman Islands than previously suggested, but cannot reject the very early peopling scenario. We further demonstrate a widespread overlap of mtDNA and cultural markers between the two major language groups of the Andaman archipelago. Given the "completeness" of the genealogy based on whole genome sequences, and the multiple scenarios for the peopling of the Andaman Islands sustained by this inferred genealogy, our study hints that further mtDNA based phylogeographic studies are unlikely to unequivocally support any one of these possibilities. (c) 2008 Wiley-Liss, Inc.

Evolutionary history of the European whitefish Coregonus lavaretus (L.) species complex as inferred from mtDNA phylogeography and gill-raker numbers.

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Østbye, K; Bernatchez, L; Naesje, T F; Himberg, K-J M; Hindar, K

2005-12-01

We compared mitochondrial DNA and gill-raker number variation in populations of the European whitefish Coregonus lavaretus (L.) species complex to illuminate their evolutionary history, and discuss mechanisms behind diversification. Using single-strand conformation polymorphism (SSCP) and sequencing 528 bp of combined parts of the cytochrome oxidase b (cyt b) and NADH dehydrogenase subunit 3 (ND3) mithochondrial DNA (mtDNA) regions, we documented phylogeographic relationships among populations and phylogeny of mtDNA haplotypes. Demographic events behind geographical distribution of haplotypes were inferred using nested clade analysis (NCA) and mismatch distribution. Concordance between operational taxonomical groups, based on gill-raker numbers, and mtDNA patterns was tested. Three major mtDNA clades were resolved in Europe: a North European clade from northwest Russia to Denmark, a Siberian clade from the Arctic Sea to southwest Norway, and a South European clade from Denmark to the European Alps, reflecting occupation in different glacial refugia. Demographic events inferred from NCA were isolation by distance, range expansion, and fragmentation. Mismatch analysis suggested that clades which colonized Fennoscandia and the Alps expanded in population size 24 500-5800 years before present, with minute female effective population sizes, implying small founder populations during colonization. Gill-raker counts did not commensurate with hierarchical mtDNA clades, and poorly with haplotypes, suggesting recent origin of gill-raker variation. Whitefish designations based on gill-raker numbers were not associated with ancient clades. Lack of congruence in morphology and evolutionary lineages implies that the taxonomy of this species complex should be reconsidered.

The Landscape of mtDNA Modifications in Cancer: A Tale of Two Cities.

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Hertweck, Kate L; Dasgupta, Santanu

2017-01-01

Mitochondria from normal and cancerous cells represent a tale of two cities, wherein both execute similar processes but with different cellular and molecular effects. Given the number of reviews currently available which describe the functional implications of mitochondrial mutations in cancer, this article focuses on documenting current knowledge in the abundance and distribution of somatic mitochondrial mutations, followed by elucidation of processes which affect the fate of mutations in cancer cells. The conclusion includes an overview of translational implications for mtDNA mutations, as well as recommendations for future research uniting mitochondrial variants and tumorigenesis.

MtDNA diversity among four Portuguese autochthonous dog breeds: a fine-scale characterisation

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Santa-Rita Pedro

2005-06-01

Full Text Available Abstract Background The picture of dog mtDNA diversity, as obtained from geographically wide samplings but from a small number of individuals per region or breed, has revealed weak geographic correlation and high degree of haplotype sharing between very distant breeds. We aimed at a more detailed picture through extensive sampling (n = 143 of four Portuguese autochthonous breeds – Castro Laboreiro Dog, Serra da Estrela Mountain Dog, Portuguese Sheepdog and Azores Cattle Dog-and comparatively reanalysing published worldwide data. Results Fifteen haplotypes belonging to four major haplogroups were found in these breeds, of which five are newly reported. The Castro Laboreiro Dog presented a 95% frequency of a new A haplotype, while all other breeds contained a diverse pool of existing lineages. The Serra da Estrela Mountain Dog, the most heterogeneous of the four Portuguese breeds, shared haplotypes with the other mainland breeds, while Azores Cattle Dog shared no haplotypes with the other Portuguese breeds. A review of mtDNA haplotypes in dogs across the world revealed that: (a breeds tend to display haplotypes belonging to different haplogroups; (b haplogroup A is present in all breeds, and even uncommon haplogroups are highly dispersed among breeds and continental areas; (c haplotype sharing between breeds of the same region is lower than between breeds of different regions and (d genetic distances between breeds do not correlate with geography. Conclusion MtDNA haplotype sharing occurred between Serra da Estrela Mountain dogs (with putative origin in the centre of Portugal and two breeds in the north and south of the country-with the Castro Laboreiro Dog (which behaves, at the mtDNA level, as a sub-sample of the Serra da Estrela Mountain Dog and the southern Portuguese Sheepdog. In contrast, the Azores Cattle Dog did not share any haplotypes with the other Portuguese breeds, but with dogs sampled in Northern Europe. This suggested that the

MtDNA variation in the Altai-Kizhi population of southern Siberia: a synthesis of genetic variation.

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Phillips-Krawczak, Christine; Devor, Eric; Zlojutro, Mark; Moffat-Wilson, Kristin; Crawford, Michael H

2006-08-01

The native peoples of Gorno Altai in southern Siberia represent a genetically diverse population and have been of great interest to anthropological genetics. In particular, the southern Altaian population is argued to be the best candidate for the New World ancestral population. In this study we sampled Altai-Kizhi from the southern Altaian village of Mendur-Sokkon, analyzed mtDNA RFLP markers and HVS-I sequences, and compared the results to other published mtDNA data from Derenko et al. (2003) and Shields et al. (1993) encompassing the same region. Because each independent study uses different sampling techniques in characterizing gene pools, in this paper we explore the accuracy and reliability of evolutionary studies on human populations. All the major Native American haplogroups (A, B, C, and D) were identified in the Mendur-Sokkon sample, including a single individual belonging to haplogroup X. The most common mtDNA lineages are C (35.7%) and D (13.3%), which is consistent with the haplogroup profiles of neighboring Siberian groups. The Mendur-Sokkon sample exhibits depressed HVS-I diversity values and neutrality test scores, which starkly differs from the Derenko et al. (2003) data set and more closely resembles the results for neighboring south Siberian groups. Furthermore, the multidimensional scaling plot of DA genetic distances does not cluster the Altai samples, showing different genetic affinities with various Asian groups. The findings underscore the importance of sampling strategy in the reconstruction of evolutionary history at the population level.

Decreased Circulating mtDNA Levels in Professional Male Volleyball Players.

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Nasi, Milena; Cristani, Alessandro; Pinti, Marcello; Lamberti, Igor; Gibellini, Lara; De Biasi, Sara; Guazzaloca, Alessandro; Trenti, Tommaso; Cossarizza, Andrea

2016-01-01

Exercise exerts various effects on the immune system, and evidence is emerging on its anti-inflammatory effects; the mechanisms on the basis of these modifications are poorly understood. Mitochondrial DNA (mtDNA) released from damaged cells acts as a molecule containing the so-called damage-associated molecular patterns and can trigger sterile inflammation. Indeed, high plasma levels of mtDNA are associated to several inflammatory conditions and physiological aging and longevity. The authors evaluated plasma mtDNA in professional male volleyball players during seasonal training and the possible correlation between mtDNA levels and clinical parameters, body composition, and physical performance. Plasma mtDNA was quantified by real-time PCR every 2 mo in 12 professional volleyball players (PVPs) during 2 consecutive seasons. As comparison, 20 healthy nonathlete male volunteers (NAs) were analyzed. The authors found lower levels of mtDNA in plasma of PVPs than in NAs. However, PVPs showed a decrease of circulating mtDNA only in the first season, while no appreciable variations were observed during the second season. No correlation was observed among mtDNA, hematochemical, and anthropometric parameters. Regular physical activity appeared associated with lower levels of circulating mtDNA, further confirming the protective, anti-inflammatory effect of exercise.

Most of the extant mtDNA boundaries in South and Southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans

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Mastana Sarabjit

2004-08-01

Full Text Available Abstract Background Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia. Results Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades. Conclusions Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent.

Phylogeographic structure and demographic patterns of brown trout in North-West Africa.

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Snoj, Aleš; Marić, Saša; Bajec, Simona Sušnik; Berrebi, Patrick; Janjani, Said; Schöffmann, Johannes

2011-10-01

The objectives of the study were to determine the phylogeographic structure of brown trout (Salmo trutta) in Morocco, elucidate their colonization patterns in North-West Africa and identify the mtDNA lineages involved in this process. We also aimed to resolve whether certain brown trout entities are also genetically distinct. Sixty-two brown trout from eleven locations across the Mediterranean and the Atlantic drainages in Morocco were surveyed using sequence analysis of the mtDNA control region and nuclear gene LDH, and by genotyping twelve microsatellite loci. Our study confirms that in Morocco both the Atlantic and Mediterranean basins are populated by Atlantic mtDNA lineage brown trout only, demonstrating that the Atlantic lineage (especially its southern clade) invaded initially not only the western part of the Mediterranean basin in Morocco but also expanded deep into the central area. Atlantic haplotypes identified here sort into three distinct groups suggesting Morocco was colonized in at least three successive waves (1.2, 0.4 and 0.2-0.1 MY ago). This notion becomes more pronounced with the finding of a distinct haplotype in the Dades river system, whose origin appears to coalesce with the nascent stage of the basal mtDNA evolutionary lineages of brown trout. According to our results, Salmo akairos, Salmo pellegrini and "green trout" from Lake Isli do not exhibited any character states that distinctively separate them from the other brown trout populations studied. Therefore, their status as distinct species was not confirmed. Copyright © 2011 Elsevier Inc. All rights reserved.

Genetic diversity of the Chinese goat in the littoral zone of the Yangtze River as assessed by microsatellite and mtDNA.

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E, Guang-Xin; Zhao, Yong-Ju; Chen, Li-Peng; Ma, Yue-Hui; Chu, Ming-Xing; Li, Xiang-Long; Hong, Qiong-Hua; Li, Lan-Hui; Guo, Ji-Jun; Zhu, Lan; Han, Yan-Guo; Gao, Hui-Jiang; Zhang, Jia-Hua; Jiang, Huai-Zhi; Jiang, Cao-De; Wang, Gao-Fu; Ren, Hang-Xing; Jin, Mei-Lan; Sun, Yuan-Zhi; Zhou, Peng; Huang, Yong-Fu

2018-05-01

The objective of this study was to assess the genetic diversity and population structure of goats in the Yangtze River region using microsatellite and mtDNA to better understand the current status of those goat genetic diversity and the effects of natural landscape in fashion of domestic animal genetic diversity. The genetic variability of 16 goat populations in the littoral zone of the Yangtze River was estimated using 21 autosomal microsatellites, which revealed high diversity and genetic population clustering with a dispersed geographical distribution. A phylogenetic analysis of the mitochondrial D-loop region (482 bp) was conducted in 494 goats from the Yangtze River region. In total, 117 SNPs were reconstructed, and 173 haplotypes were identified, 94.5% of which belonged to lineages A and B. Lineages C, D, and G had lower frequencies (5.2%), and lineage F haplotypes were undetected. Several high-frequency haplotypes were shared by different ecogeographically distributed populations, and the close phylogenetic relationships among certain low-frequency haplotypes indicated the historical exchange of genetic material among these populations. In particular, the lineage G haplotype suggests that some west Asian goat genetic material may have been transferred to China via Muslim migration.

Cryptic lineage diversity, body size divergence, and sympatry in a species complex of Australian lizards (Gehyra).

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Moritz, Craig C; Pratt, Renae C; Bank, Sarah; Bourke, Gayleen; Bragg, Jason G; Doughty, Paul; Keogh, J Scott; Laver, Rebecca J; Potter, Sally; Teasdale, Luisa C; Tedeschi, Leonardo G; Oliver, Paul M

2018-01-01

Understanding the joint evolutionary and ecological underpinnings of sympatry among close relatives remains a key challenge in biology. This problem can be addressed through joint phylogenomic and phenotypic analysis of complexes of closely related lineages within, and across, species and hence representing the speciation continuum. For a complex of tropical geckos from northern Australia-Gehyra nana and close relatives-we combine mtDNA phylogeography, exon-capture sequencing, and morphological data to resolve independently evolving lineages and infer their divergence history and patterns of morphological evolution. Gehyra nana is found to include nine divergent lineages and is paraphyletic with four other species from the Kimberley region of north-west Australia. Across these 13 taxa, 12 of which are restricted to rocky habitats, several lineages overlap geographically, including on the diverse Kimberley islands. Morphological evolution is dominated by body size shifts, and both body size and shape have evolved gradually across the group. However, larger body size shifts are observed among overlapping taxa than among closely related parapatric lineages of G. nana, and sympatric lineages are more divergent than expected at random. Whether elevated body size differences among sympatric lineages are due to ecological sorting or character displacement remains to be determined. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

Analysis of Canis mitochondrial DNA demonstrates high concordance between the control region and ATPase genes

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White Bradley N

2010-07-01

Full Text Available Abstract Background Phylogenetic studies of wild Canis species have relied heavily on the mitochondrial DNA control region (mtDNA CR to infer species relationships and evolutionary lineages. Previous analyses of the CR provided evidence for a North American evolved eastern wolf (C. lycaon, that is more closely related to red wolves (C. rufus and coyotes (C. latrans than grey wolves (C. lupus. Eastern wolf origins, however, continue to be questioned. Therefore, we analyzed mtDNA from 89 wolves and coyotes across North America and Eurasia at 347 base pairs (bp of the CR and 1067 bp that included the ATPase6 and ATPase8 genes. Phylogenies and divergence estimates were used to clarify the evolutionary history of eastern wolves, and regional comparisons of nonsynonomous to synonomous substitutions (dN/dS at the ATPase6 and ATPase8 genes were used to elucidate the potential role of selection in shaping mtDNA geographic distribution. Results We found high concordance across analyses between the mtDNA regions studied. Both had a high percentage of variable sites (CR = 14.6%; ATP = 9.7% and both phylogenies clustered eastern wolf haplotypes monophyletically within a North American evolved lineage apart from coyotes. Divergence estimates suggest the putative red wolf sequence is more closely related to coyotes (DxyCR = 0.01982 ± 0.00494 SD; DxyATP = 0.00332 ± 0.00097 SD than the eastern wolf sequences (DxyCR = 0.03047 ± 0.00664 SD; DxyATP = 0.00931 ± 0.00205 SD. Neutrality tests on both genes were indicative of the population expansion of coyotes across eastern North America, and dN/dS ratios suggest a possible role for purifying selection in the evolution of North American lineages. dN/dS ratios were higher in European evolved lineages from northern climates compared to North American evolved lineages from temperate regions, but these differences were not statistically significant. Conclusions These results demonstrate high concordance between coding

A Molecular Assessment of Phylogenetic Relationships and LineageDiversification Within the Family Salamandridae (Amphibia, Caudata)

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Weisrock, David W.; Papenfuss, Theodore J.; Macey, J. Robert; Litvinchuk, Spartak N.; Polymeni, Rosa; Ugurtas, Ismail H.; Zhao, Ermi; Larson, Allan

2005-08-08

Phylogenetic relationships among species of the salamanderfamily Salamandridae are investigated using nearly 3000 nucleotide basesof newly reported mitochondrial DNA sequence data from the mtDNA genicregion spanning the genes tRNALeu-COI. This study uses nearlycomprehensive species-level sampling to provide the first completephylogeny for the Salamandridae. Deep phylogenetic relationships amongthe three most divergent lineages in the family Salamandrina terdigitata,a clade comprising the "True" salamanders, and a clade comprising allnewts except S. terdigitata are difficult to resolve. However, mostrelationships within the latter two lineages are resolved with robustlevels of branch support. The genera Euproctus and Triturus arestatistically shown to be nonmonophyletic, instead each contains adiverse set of lineages positioned within the large newt clade. The genusParamesotriton is also resolve as a nonmonophyletic group, with the newlydescribed species P. laoensis constituting a divergent lineage placed ina sister position to clade containing all Pachytriton species and allremaining Paramesotriton species. Sequence divergences between P.laoensis and other Paramesotriton species are as great as those comparingP. laoensis and species of the genera Cynops and Pachytriton. Analyses oflineage diversification across the Salamandridae indicate that, despiteits exceptional diversity, lineage accumulation appears to have beenconstant across time, indicating that it does not represent a truespecies radiation.

Metabolic rescue in pluripotent cells from patients with mtDNA disease.

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Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat

2015-08-13

Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

Nuclear DNA but not mtDNA controls tumor phenotypes in mouse cells

International Nuclear Information System (INIS)

Akimoto, Miho; Niikura, Mamoru; Ichikawa, Masami; Yonekawa, Hiromichi; Nakada, Kazuto; Honma, Yoshio; Hayashi, Jun-Ichi

2005-01-01

Recent studies showed high frequencies of homoplasmic mtDNA mutations in various human tumor types, suggesting that the mutated mtDNA haplotypes somehow contribute to expression of tumor phenotypes. We directly addressed this issue by isolating mouse mtDNA-less (ρ 0 ) cells for complete mtDNA replacement between normal cells and their carcinogen-induced transformants, and examined the effect of the mtDNA replacement on expression of tumorigenicity, a phenotype forming tumors in nude mice. The results showed that genome chimera cells carrying nuclear DNA from tumor cells and mtDNA from normal cells expressed tumorigenicity, whereas those carrying nuclear DNA from normal cells and mtDNA from tumor cells did not. These observations provided direct evidence that nuclear DNA, but not mtDNA, is responsible for carcinogen-induced malignant transformation, although it remains possible that mtDNA mutations and resultant respiration defects may influence the degree of malignancy, such as invasive or metastatic properties

Molecular phylogeography of the brown bear (Ursus arctos) in Northeastern Asia based on analyses of complete mitochondrial DNA sequences.

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Hirata, Daisuke; Mano, Tsutomu; Abramov, Alexei V; Baryshnikov, Gennady F; Kosintsev, Pavel A; Vorobiev, Alexandr A; Raichev, Evgeny G; Tsunoda, Hiroshi; Kaneko, Yayoi; Murata, Koichi; Fukui, Daisuke; Masuda, Ryuichi

2013-07-01

To further elucidate the migration history of the brown bears (Ursus arctos) on Hokkaido Island, Japan, we analyzed the complete mitochondrial DNA (mtDNA) sequences of 35 brown bears from Hokkaido, the southern Kuril Islands (Etorofu and Kunashiri), Sakhalin Island, and the Eurasian Continent (continental Russia, Bulgaria, and Tibet), and those of four polar bears. Based on these sequences, we reconstructed the maternal phylogeny of the brown bear and estimated divergence times to investigate the timing of brown bear migrations, especially in northeastern Eurasia. Our gene tree showed the mtDNA haplotypes of all 73 brown and polar bears to be divided into eight divergent lineages. The brown bear on Hokkaido was divided into three lineages (central, eastern, and southern). The Sakhalin brown bear grouped with eastern European and western Alaskan brown bears. Etorofu and Kunashiri brown bears were closely related to eastern Hokkaido brown bears and could have diverged from the eastern Hokkaido lineage after formation of the channel between Hokkaido and the southern Kuril Islands. Tibetan brown bears diverged early in the eastern lineage. Southern Hokkaido brown bears were closely related to North American brown bears.

Human mitochondrial DNA (mtDNA) types in Malaysia

International Nuclear Information System (INIS)

Lian, L.H.; Koh, C.L.; Lim, M.E.

2000-01-01

Each human cell contains hundreds of mitochondria and thousands of double-stranded circular mtDNA. The delineation of human mtDNA variation and genetics over the past decade has provided unique and often startling insights into human evolution, degenerative diseases, and aging. Each mtDNA of 16,569 base pairs, encodes 13 polypeptides essential to the enzymes of the mitochondrial energy generating pathway, plus the necessary tRNAs and rRNAs. The highly polymorphic noncoding D-(displacement) loop region, also called the control region, is approximately 1.2 kb long. It contains two well-characterized hypervariable (HV-) regions, HV1 and HV2. MtDNA identification is usually based on these sequence differences. According to the TWTGDAM (Technical Working Group for DNA Analysis Methods), the minimum requirement for a mtDNA database for HV1 is from positions 16024 to 16365 and for HV2, from positions 00073 to 00340. The targeted Malaysian population subgroups for this study were mainly the Malays, Chinese, Indians, and indigenous Ibans, Bidayuhs, Kadazan-Dusuns, and Bajaus. Research methodologies undertaken included DNA extraction of samples from unrelated individuals, amplification of the specific regions via the polymerase chain reaction (PCR), and preparation of template DNA for sequencing by using an automated DNA sequencer. Sufficient nucleotide sequence data were generated from the mtDNA analysis. When the sequences were analyzed, sequence variations were found to be caused by nucleotide substitutions, insertions, and deletions. Of the three causes of the sequence variations, nucleotide substitutions (86.1%) accounted for the vast majority of polymorphism. It is noted that transitions (83.5%) were predominant when compared to the significantly lower frequencies of transversions (2.6%). Insertions (0.9%) and deletions (13.0%) were rather rare and found only in HV2. The data generated will also form the basis of a Malaysian DNA sequence database of mtDNA D

Luminal progenitors restrict their lineage potential during mammary gland development.

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Rodilla, Veronica; Dasti, Alessandro; Huyghe, Mathilde; Lafkas, Daniel; Laurent, Cécile; Reyal, Fabien; Fre, Silvia

2015-02-01

The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes.

Association of low race performance with mtDNA haplogroup L3b of Australian thoroughbred horses.

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Lin, Xiang; Zheng, Hong-Xiang; Davie, Allan; Zhou, Shi; Wen, Li; Meng, Jun; Zhang, Yong; Aladaer, Qimude; Liu, Bin; Liu, Wu-Jun; Yao, Xin-Kui

2018-03-01

Mitochondrial DNA (mtDNA) encodes the genes for respiratory chain sub-units that determine the efficiency of oxidative phosphorylation in mitochondria. The aim of this study was to determine if there were any haplogroups and variants in mtDNA that could be associated with athletic performance of Thoroughbred horses. The whole mitochondrial genomes of 53 maternally unrelated Australian Thoroughbred horses were sequenced and an association study was performed with the competition histories of 1123 horses within their maternal lineages. A horse mtDNA phylogenetic tree was constructed based on a total of 195 sequences (including 142 from previous reports). The association analysis showed that the sample groups with poor racing performance history were enriched in haplogroup L3b (p = .0003) and its sub-haplogroup L3b1a (p = .0007), while those that had elite performance appeared to be not significantly associated with haplogroups G2 and L3a1a1a (p > .05). Haplogroup L3b and L3b1a bear two and five specific variants of which variant T1458C (site 345 in 16s rRNA) is the only potential functional variant. Furthermore, secondary reconstruction of 16s RNA showed considerable differences between two types of 16s RNA molecules (with and without T1458C), indicating a potential functional effect. The results suggested that haplogroup L3b, could have a negative association with elite performance. The T1458C mutation harboured in haplogroup L3b could have a functional effect that is related to poor athletic performance.

Two distinct mtDNA lineages of the blue crab reveal large-scale population structure in its native Atlantic distribution

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Alaniz Rodrigues, Marcos; Dumont, Luiz Felipe Cestari; dos Santos, Cléverson Rannieri Meira; D'Incao, Fernando; Weiss, Steven; Froufe, Elsa

2017-10-01

For the first time, a molecular approach was used to evaluate the phylogenetic structure of the disjunct native American distribution of the blue crab Callinectes sapidus. Population structure was investigated by sequencing 648bp of the Cytochrome oxidase subunit 1 (COI), in a total of 138 sequences stemming from individual samples from both the northern and southern hemispheres of the Western Atlantic distribution of the species. A Bayesian approach was used to construct a phylogenetic tree for all samples, and a 95% confidence parsimony network was created to depict the relationship among haplotypes. Results revealed two highly distinct lineages, one containing all samples from the United States and some from Brazil (lineage 1) and the second restricted to Brazil (lineage 2). In addition, gene flow (at least for females) was detected among estuaries at local scales and there is evidence for shared haplotypes in the south. Furthermore, the findings of this investigation support the contemporary introduction of haplotypes that have apparently spread from the south to the north Atlantic.

mtDNA, Metastasis, and the Mitochondrial Unfolded Protein Response (UPRmt).

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Kenny, Timothy C; Germain, Doris

2017-01-01

While several studies have confirmed a link between mitochondrial DNA (mtDNA) mutations and cancer cell metastasis, much debate remains regarding the nature of the alternations in mtDNA leading to this effect. Meanwhile, the mitochondrial unfolded protein response (UPR mt ) has gained much attention in recent years, with most studies of this pathway focusing on its role in aging. However, the UPR mt has also been studied in the context of cancer. More recent work suggests that rather than a single mutation or alternation, specific combinatorial mtDNA landscapes able to activate the UPR mt may be those that are selected by metastatic cells, while mtDNA landscapes unable to activate the UPR mt do not. This review aims at offering an overview of the confusing literature on mtDNA mutations and metastasis and the more recent work on the UPR mt in this setting.

Optimized mtDNA Control Region Primer Extension Capture Analysis for Forensically Relevant Samples and Highly Compromised mtDNA of Different Age and Origin

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Mayra Eduardoff

2017-09-01

Full Text Available The analysis of mitochondrial DNA (mtDNA has proven useful in forensic genetics and ancient DNA (aDNA studies, where specimens are often highly compromised and DNA quality and quantity are low. In forensic genetics, the mtDNA control region (CR is commonly sequenced using established Sanger-type Sequencing (STS protocols involving fragment sizes down to approximately 150 base pairs (bp. Recent developments include Massively Parallel Sequencing (MPS of (multiplex PCR-generated libraries using the same amplicon sizes. Molecular genetic studies on archaeological remains that harbor more degraded aDNA have pioneered alternative approaches to target mtDNA, such as capture hybridization and primer extension capture (PEC methods followed by MPS. These assays target smaller mtDNA fragment sizes (down to 50 bp or less, and have proven to be substantially more successful in obtaining useful mtDNA sequences from these samples compared to electrophoretic methods. Here, we present the modification and optimization of a PEC method, earlier developed for sequencing the Neanderthal mitochondrial genome, with forensic applications in mind. Our approach was designed for a more sensitive enrichment of the mtDNA CR in a single tube assay and short laboratory turnaround times, thus complying with forensic practices. We characterized the method using sheared, high quantity mtDNA (six samples, and tested challenging forensic samples (n = 2 as well as compromised solid tissue samples (n = 15 up to 8 kyrs of age. The PEC MPS method produced reliable and plausible mtDNA haplotypes that were useful in the forensic context. It yielded plausible data in samples that did not provide results with STS and other MPS techniques. We addressed the issue of contamination by including four generations of negative controls, and discuss the results in the forensic context. We finally offer perspectives for future research to enable the validation and accreditation of the PEC MPS

Global mtDNA genetic structure and hypothesized invasion history of a major pest of citrus, Diaphorina citri (Hemiptera: Liviidae).

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Luo, Yufa; Agnarsson, Ingi

2018-01-01

The Asian citrus psyllid Diaphorina citri Kuwayama is a key pest of citrus as the vector of the bacterium causing the "huanglongbing" disease (HLB). To assess the global mtDNA population genetic structure, and possible dispersal history of the pest, we investigated genetic variation at the COI gene collating newly collected samples with all previously published data. Our dataset consists of 356 colonies from 106 geographic sites worldwide. High haplotype diversity (H-mean = 0.702 ± 0.017), low nucleotide diversity (π-mean = 0.003), and significant positive selection (Ka/Ks = 32.92) were observed. Forty-four haplotypes (Hap) were identified, clustered into two matrilines: Both occur in southeastern and southern Asia, North and South America, and Africa; lineages A and B also occur in eastern and western Asia, respectively. The most abundant haplotypes were Hap4 in lineage A (35.67%), and Hap9 in lineage B (41.29%). The haplotype network identified them as the ancestral haplotypes within their respective lineages. Analysis of molecular variance showed significant genetic structure ( F ST  = 0.62, p  analysis suggests geographic structuring. We hypothesize a southern and/or southeastern Asia origin, three dispersal routes, and parallel expansions of two lineages. The hypothesized first route involved the expansion of lineage B from southern Asia into North America via West Asia. The second, the expansion of some lineage A individuals from Southeast Asia into East Asia, and the third involved both lineages from Southeast Asia spreading westward into Africa and subsequently into South America. To test these hypotheses and gain a deeper understanding of the global history of D. citri , more data-rich approaches will be necessary from the ample toolkit of next-generation sequencing (NGS). However, this study may serve to guide such sampling and in the development of biological control programs against the global pest D. citri .

Genetic origin, admixture, and asymmetry in maternal and paternal human lineages in Cuba

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Martínez-Fuentes Antonio

2008-07-01

Full Text Available Abstract Background Before the arrival of Europeans to Cuba, the island was inhabited by two Native American groups, the Tainos and the Ciboneys. Most of the present archaeological, linguistic and ancient DNA evidence indicates a South American origin for these populations. In colonial times, Cuban Native American people were replaced by European settlers and slaves from Africa. It is still unknown however, to what extent their genetic pool intermingled with and was 'diluted' by the arrival of newcomers. In order to investigate the demographic processes that gave rise to the current Cuban population, we analyzed the hypervariable region I (HVS-I and five single nucleotide polymorphisms (SNPs in the mitochondrial DNA (mtDNA coding region in 245 individuals, and 40 Y-chromosome SNPs in 132 male individuals. Results The Native American contribution to present-day Cubans accounted for 33% of the maternal lineages, whereas Africa and Eurasia contributed 45% and 22% of the lineages, respectively. This Native American substrate in Cuba cannot be traced back to a single origin within the American continent, as previously suggested by ancient DNA analyses. Strikingly, no Native American lineages were found for the Y-chromosome, for which the Eurasian and African contributions were around 80% and 20%, respectively. Conclusion While the ancestral Native American substrate is still appreciable in the maternal lineages, the extensive process of population admixture in Cuba has left no trace of the paternal Native American lineages, mirroring the strong sexual bias in the admixture processes taking place during colonial times.

Between the Balkans and the Baltic: Phylogeography of a Common Vole Mitochondrial DNA Lineage Limited to Central Europe.

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Stojak, Joanna; McDevitt, Allan D; Herman, Jeremy S; Kryštufek, Boris; Uhlíková, Jitka; Purger, Jenő J; Lavrenchenko, Leonid A; Searle, Jeremy B; Wójcik, Jan M

2016-01-01

The common vole (Microtus arvalis) has been a model species of small mammal for studying end-glacial colonization history. In the present study we expanded the sampling from central and eastern Europe, analyzing contemporary genetic structure to identify the role of a potential 'northern glacial refugium', i.e. a refugium at a higher latitude than the traditional Mediterranean refugia. Altogether we analyzed 786 cytochrome b (cytb) sequences (representing mitochondrial DNA; mtDNA) from the whole of Europe, adding 177 new sequences from central and eastern Europe, and we conducted analyses on eight microsatellite loci for 499 individuals (representing nuclear DNA) from central and eastern Europe, adding data on 311 new specimens. Our new data fill gaps in the vicinity of the Carpathian Mountains, the potential northern refugium, such that there is now dense sampling from the Balkans to the Baltic Sea. Here we present evidence that the Eastern mtDNA lineage of the common vole was present in the vicinity of this Carpathian refugium during the Last Glacial Maximum and the Younger Dryas. The Eastern lineage expanded from this refugium to the Baltic and shows low cytb nucleotide diversity in those most northerly parts of the distribution. Analyses of microsatellites revealed a similar pattern but also showed little differentiation between all of the populations sampled in central and eastern Europe.

Melanesian mtDNA complexity.

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Jonathan S Friedlaender

Full Text Available Melanesian populations are known for their diversity, but it has been hard to grasp the pattern of the variation or its underlying dynamic. Using 1,223 mitochondrial DNA (mtDNA sequences from hypervariable regions 1 and 2 (HVR1 and HVR2 from 32 populations, we found the among-group variation is structured by island, island size, and also by language affiliation. The more isolated inland Papuan-speaking groups on the largest islands have the greatest distinctions, while shore dwelling populations are considerably less diverse (at the same time, within-group haplotype diversity is less in the most isolated groups. Persistent differences between shore and inland groups in effective population sizes and marital migration rates probably cause these differences. We also add 16 whole sequences to the Melanesian mtDNA phylogenies. We identify the likely origins of a number of the haplogroups and ancient branches in specific islands, point to some ancient mtDNA connections between Near Oceania and Australia, and show additional Holocene connections between Island Southeast Asia/Taiwan and Island Melanesia with branches of haplogroup E. Coalescence estimates based on synonymous transitions in the coding region suggest an initial settlement and expansion in the region at approximately 30-50,000 years before present (YBP, and a second important expansion from Island Southeast Asia/Taiwan during the interval approximately 3,500-8,000 YBP. However, there are some important variance components in molecular dating that have been overlooked, and the specific nature of ancestral (maternal Austronesian influence in this region remains unresolved.

Traces of sub-Saharan and Middle Eastern lineages in Indian Muslim populations

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Eaaswarkhanth, Muthukrishnan; Haque, Ikramul; Ravesh, Zeinab; Romero, Irene Gallego; Meganathan, Poorlin Ramakodi; Dubey, Bhawna; Khan, Faizan Ahmed; Chaubey, Gyaneshwer; Kivisild, Toomas; Tyler-Smith, Chris; Singh, Lalji; Thangaraj, Kumarasamy

2010-01-01

Islam is the second most practiced religion in India, next to Hinduism. It is still unclear whether the spread of Islam in India has been only a cultural transformation or is associated with detectable levels of gene flow. To estimate the contribution of West Asian and Arabian admixture to Indian Muslims, we assessed genetic variation in mtDNA, Y-chromosomal and LCT/MCM6 markers in 472, 431 and 476 samples, respectively, representing six Muslim communities from different geographical regions of India. We found that most of the Indian Muslim populations received their major genetic input from geographically close non-Muslim populations. However, low levels of likely sub-Saharan African, Arabian and West Asian admixture were also observed among Indian Muslims in the form of L0a2a2 mtDNA and E1b1b1a and J*(xJ2) Y-chromosomal lineages. The distinction between Iranian and Arabian sources was difficult to make with mtDNA and the Y chromosome, as the estimates were highly correlated because of similar gene pool compositions in the sources. In contrast, the LCT/MCM6 locus, which shows a clear distinction between the two sources, enabled us to rule out significant gene flow from Arabia. Overall, our results support a model according to which the spread of Islam in India was predominantly cultural conversion associated with minor but still detectable levels of gene flow from outside, primarily from Iran and Central Asia, rather than directly from the Arabian Peninsula. PMID:19809480

Myopathic mtDNA Depletion Syndrome Due to Mutation in TK2 Gene.

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Martín-Hernández, Elena; García-Silva, María Teresa; Quijada-Fraile, Pilar; Rodríguez-García, María Elena; Rivera, Henry; Hernández-Laín, Aurelio; Coca-Robinot, David; Fernández-Toral, Joaquín; Arenas, Joaquín; Martín, Miguel A; Martínez-Azorín, Francisco

2017-01-01

Whole-exome sequencing was used to identify the disease gene(s) in a Spanish girl with failure to thrive, muscle weakness, mild facial weakness, elevated creatine kinase, deficiency of mitochondrial complex III and depletion of mtDNA. With whole-exome sequencing data, it was possible to get the whole mtDNA sequencing and discard any pathogenic variant in this genome. The analysis of whole exome uncovered a homozygous pathogenic mutation in thymidine kinase 2 gene ( TK2; NM_004614.4:c.323 C>T, p.T108M). TK2 mutations have been identified mainly in patients with the myopathic form of mtDNA depletion syndromes. This patient presents an atypical TK2-related myopathic form of mtDNA depletion syndromes, because despite having a very low content of mtDNA (TK2 gene in mtDNA depletion syndromes and expanded the phenotypic spectrum.

Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

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Keeney Paula M

2009-09-01

Full Text Available Abstract Background Sporadic Parkinson's disease (sPD is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA, heteroplasmic mtDNA point mutations and levels of electron transport chain proteins. We sought to determine if sPD brains possess any mtDNA genotype-respiratory phenotype relationships. Results Treatment of sPD brain mtDNA with the mitochondrial base-excision repair enzyme 8-oxyguanosine glycosylase-1 (hOGG1 inhibited, in an age-dependent manner, qPCR amplification of overlapping ~2 kbase products; amplification of CTL brain mtDNA showed moderate sensitivity to hOGG1 not dependent on donor age. hOGG1 mRNA expression was not different between sPD and CTL brains. Heteroplasmy analysis of brain mtDNA using Surveyor nuclease® showed asymmetric distributions and levels of heteroplasmic mutations across mtDNA but no patterns that statistically distinguished sPD from CTL. sPD brain mitochondria displayed reductions of nine respirasome proteins (respiratory complexes I-V. Reduced levels of sPD brain mitochondrial complex II, III and V, but not complex I or IV proteins, correlated closely with rates of NADH-driven electron flow. mtDNA levels and PGC-1α expression did not differ between sPD and CTL brains. Conclusion PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age

Phylogeography of mtDNA haplogroup R7 in the Indian peninsula

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Shukla Parul

2008-08-01

Full Text Available Abstract Background Human genetic diversity observed in Indian subcontinent is second only to that of Africa. This implies an early settlement and demographic growth soon after the first 'Out-of-Africa' dispersal of anatomically modern humans in Late Pleistocene. In contrast to this perspective, linguistic diversity in India has been thought to derive from more recent population movements and episodes of contact. With the exception of Dravidian, which origin and relatedness to other language phyla is obscure, all the language families in India can be linked to language families spoken in different regions of Eurasia. Mitochondrial DNA and Y chromosome evidence has supported largely local evolution of the genetic lineages of the majority of Dravidian and Indo-European speaking populations, but there is no consensus yet on the question of whether the Munda (Austro-Asiatic speaking populations originated in India or derive from a relatively recent migration from further East. Results Here, we report the analysis of 35 novel complete mtDNA sequences from India which refine the structure of Indian-specific varieties of haplogroup R. Detailed analysis of haplogroup R7, coupled with a survey of ~12,000 mtDNAs from caste and tribal groups over the entire Indian subcontinent, reveals that one of its more recently derived branches (R7a1, is particularly frequent among Munda-speaking tribal groups. This branch is nested within diverse R7 lineages found among Dravidian and Indo-European speakers of India. We have inferred from this that a subset of Munda-speaking groups have acquired R7 relatively recently. Furthermore, we find that the distribution of R7a1 within the Munda-speakers is largely restricted to one of the sub-branches (Kherwari of northern Munda languages. This evidence does not support the hypothesis that the Austro-Asiatic speakers are the primary source of the R7 variation. Statistical analyses suggest a significant correlation between

Neurotoxicity of cytarabine (Ara-C) in dorsal root ganglion neurons originates from impediment of mtDNA synthesis and compromise of mitochondrial function.

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Zhuo, Ming; Gorgun, Murat F; Englander, Ella W

2018-06-01

Peripheral Nervous System (PNS) neurotoxicity caused by cancer drugs hinders attainment of chemotherapy goals. Due to leakiness of the blood nerve barrier, circulating chemotherapeutic drugs reach PNS neurons and adversely affect their function. Chemotherapeutic drugs are designed to target dividing cancer cells and mechanisms underlying their toxicity in postmitotic neurons remain to be fully clarified. The objective of this work was to elucidate progression of events triggered by antimitotic drugs in postmitotic neurons. For proof of mechanism study, we chose cytarabine (ara-C), an antimetabolite used in treatment of hematological cancers. Ara-C is a cytosine analog that terminates DNA synthesis. To investigate how ara-C affects postmitotic neurons, which replicate mitochondrial but not genomic DNA, we adapted a model of Dorsal Root Ganglion (DRG) neurons. We showed that DNA polymerase γ, which is responsible for mtDNA synthesis, is inhibited by ara-C and that sublethal ara-C exposure of DRG neurons leads to reduction in mtDNA content, ROS generation, oxidative mtDNA damage formation, compromised mitochondrial respiration and diminution of NADPH and GSH stores, as well as, activation of the DNA damage response. Hence, it is plausible that in ara-C exposed DRG neurons, ROS amplified by the high mitochondrial content shifts from physiologic to pathologic levels signaling stress to the nucleus. Combined, the findings suggest that ara-C neurotoxicity in DRG neurons originates in mitochondria and that continuous mtDNA synthesis and reliance on oxidative phosphorylation for energy needs sensitize the highly metabolic neurons to injury by mtDNA synthesis terminating cancer drugs. Copyright © 2018 Elsevier Inc. All rights reserved.

Lake Tanganyika--a 'melting pot' of ancient and young cichlid lineages (Teleostei: Cichlidae?

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Juliane D Weiss

Full Text Available A long history of research focused on the East Africa cichlid radiations (EAR revealed discrepancies between mtDNA and nuclear phylogenies, suggesting that interspecific hybridisation may have been significant during the radiation of these fishes. The approximately 250 cichlid species of Lake Tanganyika have their roots in a monophyletic African cichlid assemblage, but controversies remain about the precise phylogenetic origin and placement of different lineages and consequently about L. Tanganyika colonization scenarios. 3312 AFLP loci and the mitochondrial ND2 gene were genotyped for 91 species representing almost all major lacustrine and riverine haplotilapiine east African cichlid lineages with a focus on L. Tanganyika endemics. Explicitly testing for the possibility of ancient hybridisation events, a comprehensive phylogenetic network hypothesis is proposed for the origin and diversification of L. Tanganyika cichlids. Inference of discordant phylogenetic signal strongly suggests that the genomes of two endemic L. Tanganyika tribes, Eretmodini and Tropheini, are composed of an ancient mixture of riverine and lacustrine lineages. For the first time a strong monophyly signal of all non-haplochromine mouthbrooding species endemic to L. Tanganyika ("ancient mouthbrooders" was detected. Further, in the genomes of early diverging L. Tanganyika endemics Trematocarini, Bathybatini, Hemibatini and Boulengerochromis genetic components of other lineages belonging to the East African Radiation appear to be present. In combination with recent palaeo-geological results showing that tectonic activity in the L. Tanganyika region resulted in highly dynamic and heterogeneous landscape evolution over the Neogene and Pleistocene, the novel phylogenetic data render a single lacustrine basin as the geographical cradle of the endemic L. Tanganyika cichlid lineages unlikely. Instead a scenario of a pre-rift origin of several independent L. Tanganyika precursor

Molecular ecology of the big brown bat (Eptesicus fuscus): Genetic and natural history variation in a hybrid zone

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Neubaum, M.A.; Douglas, M.R.; Douglas, M.E.; O'Shea, T.J.

2007-01-01

Several geographically distinct mitochondrial DNA (mtDNA) lineages of the big brown bat (Eptesicus fuscus) have been documented in North America. Individuals from 2 of these lineages, an eastern and a western form, co-occur within maternity colonies in Colorado. The discovery of 2 divergent mtDNA lineages in sympatry prompted a set of questions regarding possible biological differences between haplotypes. We captured big brown bats at maternity roosts in Colorado and recorded data on body size, pelage color, litter size, roosting and overwintering behaviors, and local distributions. Wing biopsies were collected for genetic analysis. The ND2 region of the mtDNA molecule was used to determine lineage of the bats. In addition, nuclear DNA (nDNA) intron 1 of the ??-globin gene was used to determine if mtDNA lineages are hybridizing. Eastern and western mtDNA lineages differed by 10.3% sequence divergence and examination of genetic data suggests recent population expansion for both lineages. Differences in distribution occur along the Colorado Front Range, with an increasing proportion of western haplotypes farther south. Results from nDNA analyses demonstrated hybridization between the 2 lineages. Additionally, no outstanding distinctiveness was found between the mtDNA lineages in natural history characters examined. We speculate that historical climate changes separated this species into isolated eastern and western populations, and that secondary contact with subsequent interbreeding was facilitated by European settlement. ?? 2007 American Society of Mammalogists.

Mitochondrial DNA copy number threshold in mtDNA depletion myopathy.

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Durham, S E; Bonilla, E; Samuels, D C; DiMauro, S; Chinnery, P F

2005-08-09

The authors measured the absolute amount of mitochondrial DNA (mtDNA) within single muscle fibers from two patients with thymidine kinase 2 (TK2) deficiency and two healthy controls. TK2 deficient fibers containing more than 0.01 mtDNA/microm3 had residual cytochrome c oxidase (COX) activity. This defines the minimum amount of wild-type mtDNA molecules required to maintain COX activity in skeletal muscle and provides an explanation for the mosaic histochemical pattern seen in patients with mtDNA depletion syndrome.

Hypervariable region polymorphism of mtDNA of recurrent oral ulceration in Chinese.

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Mao Sun

Full Text Available BACKGROUND: MtDNA haplogroups could have important implication for understanding of the relationship between the mutations of the mitochondrial genome and diseases. Distribution of a variety of diseases among these haplogroups showed that some of the mitochondrial haplogroups are predisposed to disease. To examine the susceptibility of mtDNA haplogroups to ROU, we sequenced the mtDNA HV1, HV2 and HV3 in Chinese ROU. METHODOLOGY/PRINCIPAL FINDINGS: MtDNA haplogroups were analyzed in the 249 cases of ROU patients and the 237 cases of healthy controls respectively by means of primer extension analysis and DNA sequencing. Haplogroups G1 and H were found significantly more abundant in ROU patients than in healthy persons, while haplogroups D5 and R showed a trend toward a higher frequency in control as compared to those in patients. The distribution of C-stretch sequences polymorphism in mtDNA HV1, HV2 and HV3 regions was found in diversity. CONCLUSIONS/SIGNIFICANCE: For the first time, the relationship of mtDNA haplogroups and ROU in Chinese was investigated. Our results indicated that mtDNA haplogroups G1 and H might constitute a risk factor for ROU, which possibly increasing the susceptibility of ROU. Meanwhile, haplogroups D5 and R were indicated as protective factors for ROU. The polymorphisms of C-stretch sequences might being unstable and influence the mtDNA replication fidelity.

Demography or selection on linked cultural traits or genes? Investigating the driver of low mtDNA diversity in the sperm whale using complementary mitochondrial and nuclear genome analyses.

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Morin, Phillip A; Foote, Andrew D; Baker, C Scott; Hancock-Hanser, Brittany L; Kaschner, Kristin; Mate, Bruce R; Mesnick, Sarah L; Pease, Victoria L; Rosel, Patricia E; Alexander, Alana

2018-04-19

Mitochondrial DNA has been heavily utilized in phylogeography studies for several decades. However, underlying patterns of demography and phylogeography may be misrepresented due to coalescence stochasticity, selection, variation in mutation rates, and cultural hitchhiking (linkage of genetic variation to culturally transmitted traits affecting fitness). Cultural hitchhiking has been suggested as an explanation for low genetic diversity in species with strong social structures, counteracting even high mobility, abundance and limited barriers to dispersal. One such species is the sperm whale, which shows very limited phylogeographic structure and low mtDNA diversity despite a worldwide distribution and large population. Here, we use analyses of 175 globally distributed mitogenomes and three nuclear genomes to evaluate hypotheses of a population bottleneck/expansion versus a selective sweep due to cultural-hitchhiking or selection on mtDNA as the mechanism contributing to low worldwide mitochondrial diversity in sperm whales. In contrast to mtDNA control region (CR) data, mitogenome haplotypes are largely ocean-specific, with only one of 80 shared between the Atlantic and Pacific. Demographic analyses of nuclear genomes suggest low mtDNA diversity is consistent with a global reduction in population size that ended approximately 125,000 years ago, correlated with the Eemian interglacial. Phylogeographic analysis suggests that extant sperm whales descend from maternal lineages endemic to the Pacific during the period of reduced abundance, and have subsequently colonized the Atlantic several times. Results highlight the apparent impact of past climate change, and suggest selection and hitchhiking are not the sole processes responsible for low mtDNA diversity in this highly social species. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Possible conservation units of the sun bear (Helarctos malayanus) in Sarawak based on variation of mtDNA control region.

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Onuma, Manabu; Suzuki, Masatsugu; Ohtaishi, Noriyuki

2006-11-01

The mitochondrial DNA control region of the sun bear (Helarctos malayanus) was sequenced using 21 DNA samples collected from confiscated sun bears to identify conservation units, such as evolutionarily significant units and management units, in Sarawak, Borneo Island. A total of 10 haplotypes were observed, indicating the presence of at least two lineages in the sun bear population in Sarawak. Presumably, these two lineages could represent evolutionarily significant units. However, the geographical distributions of the two lineages remained unknown due to the lack of information regarding the exact capture locations of the confiscated sun bears. It is essential to elucidate the geographical distributions of these lineages in order to create a proper conservation plan for the sun bears in Sarawak. Therefore, further studies examining the haplotype distributions using DNA samples from known localities are essential.

Brown and polar bear Y chromosomes reveal extensive male-biased gene flow within brother lineages.

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Bidon, Tobias; Janke, Axel; Fain, Steven R; Eiken, Hans Geir; Hagen, Snorre B; Saarma, Urmas; Hallström, Björn M; Lecomte, Nicolas; Hailer, Frank

2014-06-01

Brown and polar bears have become prominent examples in phylogeography, but previous phylogeographic studies relied largely on maternally inherited mitochondrial DNA (mtDNA) or were geographically restricted. The male-specific Y chromosome, a natural counterpart to mtDNA, has remained underexplored. Although this paternally inherited chromosome is indispensable for comprehensive analyses of phylogeographic patterns, technical difficulties and low variability have hampered its application in most mammals. We developed 13 novel Y-chromosomal sequence and microsatellite markers from the polar bear genome and screened these in a broad geographic sample of 130 brown and polar bears. We also analyzed a 390-kb-long Y-chromosomal scaffold using sequencing data from published male ursine genomes. Y chromosome evidence support the emerging understanding that brown and polar bears started to diverge no later than the Middle Pleistocene. Contrary to mtDNA patterns, we found 1) brown and polar bears to be reciprocally monophyletic sister (or rather brother) lineages, without signals of introgression, 2) male-biased gene flow across continents and on phylogeographic time scales, and 3) male dispersal that links the Alaskan ABC islands population to mainland brown bears. Due to female philopatry, mtDNA provides a highly structured estimate of population differentiation, while male-biased gene flow is a homogenizing force for nuclear genetic variation. Our findings highlight the importance of analyzing both maternally and paternally inherited loci for a comprehensive view of phylogeographic history, and that mtDNA-based phylogeographic studies of many mammals should be reevaluated. Recent advances in sequencing technology render the analysis of Y-chromosomal variation feasible, even in nonmodel organisms. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e

Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction

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Furda, Amy M.; Marrangoni, Adele M.; Lokshin, Anna; Van Houten, Bennett

2013-01-01

Mitochondrial DNA (mtDNA) is essential for proper mitochondrial function and encodes 22 tRNAs, 2 rRNAs and 13 polypeptides that make up subunits of complex I, III, IV, in the electron transport chain and complex V, the ATP synthase. Although mitochondrial dysfunction has been implicated in processes such as premature aging, neurodegeneration, and cancer, it has not been shown whether persistent mtDNA damage causes a loss of oxidative phosphorylation. We addressed this question by treating mouse embryonic fibroblasts with either hydrogen peroxide (H2O2) or the alkylating agent methyl methanesulfonate (MMS) and measuring several endpoints, including mtDNA damage and repair rates using QPCR, levels of mitochondrial- and nuclear-encoded proteins using antibody analysis, and a pharmacologic profile of mitochondria using the Seahorse Extracellular Flux Analyzer. We show that a 60 min treatment with H2O2 causes persistent mtDNA lesions, mtDNA loss, decreased levels of a nuclear-encoded mitochondrial subunit, a loss of ATP-linked oxidative phosphorylation and a loss of total reserve capacity. Conversely, a 60 min treatment with 2 mM MMS causes persistent mtDNA lesions but no mtDNA loss, no decrease in levels of a nuclear-encoded mitochondrial subunit, and no mitochondrial dysfunction. These results suggest that persistent mtDNA damage is not sufficient to cause mitochondrial dysfunction. PMID:22766155

Phylogeny and patterns of diversity of goat mtDNA haplogroup A revealed by resequencing complete mitogenomes.

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Maria Grazia Doro

Full Text Available We sequenced to near completion the entire mtDNA of 28 Sardinian goats, selected to represent the widest possible diversity of the most widespread mitochondrial evolutionary lineage, haplogroup (Hg A. These specimens were reporters of the diversity in the island but also elsewhere, as inferred from their affiliation to each of 11 clades defined by D-loop variation. Two reference sequences completed the dataset. Overall, 206 variations were found in the full set of 30 sequences, of which 23 were protein-coding non-synonymous single nucleotide substitutions. Many polymorphic sites within Hg A were informative for the reconstruction of its internal phylogeny. Bayesian and network clustering revealed a general similarity over the entire molecule of sequences previously assigned to the same D-loop clade, indicating evolutionarily meaningful lineages. Two major sister groupings emerged within Hg A, which parallel distinct geographical distributions of D-loop clades in extant stocks. The pattern of variation in protein-coding genes revealed an overwhelming role of purifying selection, with the quota of surviving variants approaching neutrality. However, a simple model of relaxation of selection for the bulk of variants here reported should be rejected. Non-synonymous diversity of Hg's A, B and C denoted that a proportion of variants not greater than that allowed in the wild was given the opportunity to spread into domesticated stocks. Our results also confirmed that a remarkable proportion of pre-existing Hg A diversity became incorporated into domestic stocks. Our results confirm clade A11 as a well differentiated and ancient lineage peculiar of Sardinia.

Y-chromosome lineages from Portugal, Madeira and Açores record elements of Sephardim and Berber ancestry.

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Gonçalves, Rita; Freitas, Ana; Branco, Marta; Rosa, Alexandra; Fernandes, Ana T; Zhivotovsky, Lev A; Underhill, Peter A; Kivisild, Toomas; Brehm, António

2005-07-01

A total of 553 Y-chromosomes were analyzed from mainland Portugal and the North Atlantic Archipelagos of Açores and Madeira, in order to characterize the genetic composition of their male gene pool. A large majority (78-83% of each population) of the male lineages could be classified as belonging to three basic Y chromosomal haplogroups, R1b, J, and E3b. While R1b, accounting for more than half of the lineages in any of the Portuguese sub-populations, is a characteristic marker of many different West European populations, haplogroups J and E3b consist of lineages that are typical of the circum-Mediterranean region or even East Africa. The highly diverse haplogroup E3b in Portuguese likely combines sub-clades of distinct origins. The present composition of the Y chromosomes in Portugal in this haplogroup likely reflects a pre-Arab component shared with North African populations or testifies, at least in part, to the influence of Sephardic Jews. In contrast to the marginally low sub-Saharan African Y chromosome component in Portuguese, such lineages have been detected at a moderately high frequency in our previous survey of mtDNA from the same samples, indicating the presence of sex-related gene flow, most likely mediated by the Atlantic slave trade.

mtDNA sequence diversity of Hazara ethnic group from Pakistan.

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Rakha, Allah; Fatima; Peng, Min-Sheng; Adan, Atif; Bi, Rui; Yasmin, Memona; Yao, Yong-Gang

2017-09-01

The present study was undertaken to investigate mitochondrial DNA (mtDNA) control region sequences of Hazaras from Pakistan, so as to generate mtDNA reference database for forensic casework in Pakistan and to analyze phylogenetic relationship of this particular ethnic group with geographically proximal populations. Complete mtDNA control region (nt 16024-576) sequences were generated through Sanger Sequencing for 319 Hazara individuals from Quetta, Baluchistan. The population sample set showed a total of 189 distinct haplotypes, belonging mainly to West Eurasian (51.72%), East & Southeast Asian (29.78%) and South Asian (18.50%) haplogroups. Compared with other populations from Pakistan, the Hazara population had a relatively high haplotype diversity (0.9945) and a lower random match probability (0.0085). The dataset has been incorporated into EMPOP database under accession number EMP00680. The data herein comprises the largest, and likely most thoroughly examined, control region mtDNA dataset from Hazaras of Pakistan. Copyright © 2017 Elsevier B.V. All rights reserved.

Minding the gap: Frequency of indels in mtDNA control region sequence data and influence on population genetic analyses

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Pearce, J.M.

2006-01-01

Insertions and deletions (indels) result in sequences of various lengths when homologous gene regions are compared among individuals or species. Although indels are typically phylogenetically informative, occurrence and incorporation of these characters as gaps in intraspecific population genetic data sets are rarely discussed. Moreover, the impact of gaps on estimates of fixation indices, such as FST, has not been reviewed. Here, I summarize the occurrence and population genetic signal of indels among 60 published studies that involved alignments of multiple sequences from the mitochondrial DNA (mtDNA) control region of vertebrate taxa. Among 30 studies observing indels, an average of 12% of both variable and parsimony-informative sites were composed of these sites. There was no consistent trend between levels of population differentiation and the number of gap characters in a data block. Across all studies, the average influence on estimates of ??ST was small, explaining only an additional 1.8% of among population variance (range 0.0-8.0%). Studies most likely to observe an increase in ??ST with the inclusion of gap characters were those with control region DNA appears small, dependent upon total number of variable sites in the data block, and related to species-specific characteristics and the spatial distribution of mtDNA lineages that contain indels. ?? 2006 Blackwell Publishing Ltd.

Application of a random walk model to geographic distributions of animal mitochondrial DNA variation.

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Neigel, J E; Avise, J C

1993-12-01

In rapidly evolving molecules, such as animal mitochondrial DNA, mutations that delineate specific lineages may not be dispersed at sufficient rates to attain an equilibrium between genetic drift and gene flow. Here we predict conditions that lead to nonequilibrium geographic distributions of mtDNA lineages, test the robustness of these predictions and examine mtDNA data sets for consistency with our model. Under a simple isolation by distance model, the variance of an mtDNA lineage's geographic distribution is expected be proportional to its age. Simulation results indicated that this relationship is fairly robust. Analysis of mtDNA data from natural populations revealed three qualitative distributional patterns: (1) significant departure of lineage structure from equilibrium geographic distributions, a pattern exhibited in three rodent species with limited dispersal; (2) nonsignificant departure from equilibrium expectations, exhibited by two avian and two marine fish species with potentials for relatively long-distance dispersal; and (3) a progression from nonequilibrium distributions for younger lineages to equilibrium distributions for older lineages, a condition displayed by one surveyed avian species. These results demonstrate the advantages of considering mutation and genealogy in the interpretation of mtDNA geographic variation.

Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

International Nuclear Information System (INIS)

Kukat, Alexandra; Edgar, Daniel; Bratic, Ivana; Maiti, Priyanka; Trifunovic, Aleksandra

2011-01-01

Highlights: → Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. → This process is independent of endogenous ROS production. → Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O 2 ) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

Mitochondrial depolarization in yeast zygotes inhibits clonal expansion of selfish mtDNA.

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Karavaeva, Iuliia E; Golyshev, Sergey A; Smirnova, Ekaterina A; Sokolov, Svyatoslav S; Severin, Fedor F; Knorre, Dmitry A

2017-04-01

Non-identical copies of mitochondrial DNA (mtDNA) compete with each other within a cell and the ultimate variant of mtDNA present depends on their relative replication rates. Using yeast Saccharomyces cerevisiae cells as a model, we studied the effects of mitochondrial inhibitors on the competition between wild-type mtDNA and mutant selfish mtDNA in heteroplasmic zygotes. We found that decreasing mitochondrial transmembrane potential by adding uncouplers or valinomycin changes the competition outcomes in favor of the wild-type mtDNA. This effect was significantly lower in cells with disrupted mitochondria fission or repression of the autophagy-related genes ATG8 , ATG32 or ATG33 , implying that heteroplasmic zygotes activate mitochondrial degradation in response to the depolarization. Moreover, the rate of mitochondrially targeted GFP turnover was higher in zygotes treated with uncoupler than in haploid cells or untreated zygotes. Finally, we showed that vacuoles of zygotes with uncoupler-activated autophagy contained DNA. Taken together, our data demonstrate that mitochondrial depolarization inhibits clonal expansion of selfish mtDNA and this effect depends on mitochondrial fission and autophagy. These observations suggest an activation of mitochondria quality control mechanisms in heteroplasmic yeast zygotes. © 2017. Published by The Company of Biologists Ltd.

Mitochondrial lineage M1 traces an early human backflow to Africa.

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González, Ana M; Larruga, José M; Abu-Amero, Khaled K; Shi, Yufei; Pestano, José; Cabrera, Vicente M

2007-07-09

The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA) sequences and 261 partial sequences belonging to haplogroup M1 was carried out. The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

Mitochondrial lineage M1 traces an early human backflow to Africa

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Pestano José

2007-07-01

Full Text Available Abstract Background The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA sequences and 261 partial sequences belonging to haplogroup M1 was carried out. Results The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. Conclusion This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

Evidence of animal mtDNA recombination between divergent populations of the potato cyst nematode Globodera pallida.

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Hoolahan, Angelique H; Blok, Vivian C; Gibson, Tracey; Dowton, Mark

2012-03-01

Recombination is typically assumed to be absent in animal mitochondrial genomes (mtDNA). However, the maternal mode of inheritance means that recombinant products are indistinguishable from their progenitor molecules. The majority of studies of mtDNA recombination assess past recombination events, where patterns of recombination are inferred by comparing the mtDNA of different individuals. Few studies assess contemporary mtDNA recombination, where recombinant molecules are observed as direct mosaics of known progenitor molecules. Here we use the potato cyst nematode, Globodera pallida, to investigate past and contemporary recombination. Past recombination was assessed within and between populations of G. pallida, and contemporary recombination was assessed in the progeny of experimental crosses of these populations. Breeding of genetically divergent organisms may cause paternal mtDNA leakage, resulting in heteroplasmy and facilitating the detection of recombination. To assess contemporary recombination we looked for evidence of recombination between the mtDNA of the parental populations within the mtDNA of progeny. Past recombination was detected between a South American population and several UK populations of G. pallida, as well as between two South American populations. This suggests that these populations may have interbred, paternal mtDNA leakage occurred, and the mtDNA of these populations subsequently recombined. This evidence challenges two dogmas of animal mtDNA evolution; no recombination and maternal inheritance. No contemporary recombination between the parental populations was detected in the progeny of the experimental crosses. This supports current arguments that mtDNA recombination events are rare. More sensitive detection methods may be required to adequately assess contemporary mtDNA recombination in animals.

Post-glacial recolonization of the Great Lakes region by the common gartersnake (Thamnophis sirtalis) inferred from mtDNA sequences.

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Placyk, John S; Burghardt, Gordon M; Small, Randall L; King, Richard B; Casper, Gary S; Robinson, Jace W

2007-05-01

Pleistocene events played an important role in the differentiation of North American vertebrate populations. Michigan, in particular, and the Great Lakes region, in general, were greatly influenced by the last glaciation. While several hypotheses regarding the recolonization of this region have been advanced, none have been strongly supported. We generated 148 complete ND2 mitochondrial DNA (mtDNA) sequences from common gartersnake (Thamnophis sirtalis) populations throughout the Great Lakes region to evaluate phylogeographic patterns and population structure and to determine whether the distribution of haplotypic variants is related to the post-Pleistocene retreat of the Wisconsinan glacier. The common gartersnake was utilized, as it is believed to have been one of the primary vertebrate invaders of the Great Lakes region following the most recent period of glacial retreat and because it has been a model species for a variety of evolutionary, ecological, behavioral, and physiological studies. Several genetically distinct evolutionary lineages were supported by both genealogical and molecular population genetic analyses, although to different degrees. The geographic distribution of the majority of these lineages is interpreted as reflecting post-glacial recolonization dynamics during the late Pleistocene. These findings generally support previous hypotheses of range expansion in this region.

The mitochondrial outer membrane protein MDI promotes local protein synthesis and mtDNA replication.

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Zhang, Yi; Chen, Yong; Gucek, Marjan; Xu, Hong

2016-05-17

Early embryonic development features rapid nuclear DNA replication cycles, but lacks mtDNA replication. To meet the high-energy demands of embryogenesis, mature oocytes are furnished with vast amounts of mitochondria and mtDNA However, the cellular machinery driving massive mtDNA replication in ovaries remains unknown. Here, we describe a Drosophila AKAP protein, MDI that recruits a translation stimulator, La-related protein (Larp), to the mitochondrial outer membrane in ovaries. The MDI-Larp complex promotes the synthesis of a subset of nuclear-encoded mitochondrial proteins by cytosolic ribosomes on the mitochondrial surface. MDI-Larp's targets include mtDNA replication factors, mitochondrial ribosomal proteins, and electron-transport chain subunits. Lack of MDI abolishes mtDNA replication in ovaries, which leads to mtDNA deficiency in mature eggs. Targeting Larp to the mitochondrial outer membrane independently of MDI restores local protein synthesis and rescues the phenotypes of mdi mutant flies. Our work suggests that a selective translational boost by the MDI-Larp complex on the outer mitochondrial membrane might be essential for mtDNA replication and mitochondrial biogenesis during oogenesis. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

No evidence of Neandertal mtDNA contribution to early modern humans.

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David Serre

2004-03-01

Full Text Available The retrieval of mitochondrial DNA (mtDNA sequences from four Neandertal fossils from Germany, Russia, and Croatia has demonstrated that these individuals carried closely related mtDNAs that are not found among current humans. However, these results do not definitively resolve the question of a possible Neandertal contribution to the gene pool of modern humans since such a contribution might have been erased by genetic drift or by the continuous influx of modern human DNA into the Neandertal gene pool. A further concern is that if some Neandertals carried mtDNA sequences similar to contemporaneous humans, such sequences may be erroneously regarded as modern contaminations when retrieved from fossils. Here we address these issues by the analysis of 24 Neandertal and 40 early modern human remains. The biomolecular preservation of four Neandertals and of five early modern humans was good enough to suggest the preservation of DNA. All four Neandertals yielded mtDNA sequences similar to those previously determined from Neandertal individuals, whereas none of the five early modern humans contained such mtDNA sequences. In combination with current mtDNA data, this excludes any large genetic contribution by Neandertals to early modern humans, but does not rule out the possibility of a smaller contribution.

The amount and integrity of mtDNA in maize decline with development.

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Oldenburg, Delene J; Kumar, Rachana A; Bendich, Arnold J

2013-02-01

In maize and other grasses there is a developmental gradient from the meristematic cells at the base of the stalk to the differentiated cells at the leaf tip. This gradient presents an opportunity to investigate changes in mitochondrial DNA (mtDNA) that accompany growth under light and dark conditions, as done previously for plastid DNA. Maize mtDNA was analyzed by DAPI-DNA staining of individual mitochondria, gel electrophoresis/blot hybridization, and real-time qPCR. Both the amount and integrity of the mtDNA were found to decline with development. There was a 20-fold decline in mtDNA copy number per cell from the embryo to the light-grown leaf blade. The amount of DNA per mitochondrial particle was greater in dark-grown leaf blade (24 copies, on average) than in the light (2 copies), with some mitochondria lacking any detectable DNA. Three factors that influence the demise of mtDNA during development are considered: (1) the decision to either repair or degrade mtDNA molecules that are damaged by the reactive oxygen species produced as byproducts of respiration; (2) the generation of ATP by photophosphorylation in chloroplasts, reducing the need for respiratory-competent mitochondria; and (3) the shift in mitochondrial function from energy-generating respiration to photorespiration during the transition from non-green to green tissue.

Do mtDNA Deletions Play a Role in the Development of Nasal Polyposis?

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Arzu Tatar

2014-04-01

Full Text Available Objective:Nasal polyposis (NP is an inflammatory disease of the nasal mucosa and paranasal sinuses. Mitochondria are the cellular organelles which produce cellular energy by Oxidative Phosphorylation (OXPHOS, and they have own inheritance material, mtDNA. mtDNA is affected by reactive oxygen samples (ROS which are produced by both OXPHOS and the inflammatory process. The aim of this study was to investigate the 4977 bp and 7400 bp deletions of mtDNA in nasal polyposis tissue, and to indicate the possible association of mtDNA deletions with NP. Methods:Thirty-three patients, aged 15 to 65 years, with nasal polyposis were selected to be assessed for mitochondrial DNA deletions. The patients with possible mtDNA mutations due to mitochondrial disease, being treated with radiotherapy, of advanced age, with a familiar history, aspirin hypersensitivity, or a history of asthma, were excluded. Polyp excision surgery was applied to the treatment of the NP, and after histopathological diagnosis 1x1 cm of polyp tissue samples were used to isolate mtDNA. The 4977 bp and 7400 bp deletion regions, and two control regions of mtDNA were assessed by using four pairs of primers. DNA extractions from the NP tissues and peripheral blood samples of the patients were made, and then Polymerase Chain Reactions (PCR were made. PCR products were separated in 2% agarose gel.Results:No patient had either the 4977 bp deletion or the 7400 bp deletion in their NP tissue, and neither were these deletions evident in their peripheral blood. Two control sequences, one of them from a non-deleted region, and the other from a possible deletion region, were detected in the NP tissues and peripheral blood of all the patients.Conclusions:We had anticipated that some mtDNA deletion might have occurred in NP tissue due to the increased ROS levels caused by chronic inflammation, but we did not detect any deletion. Probably, the duration of inflammation in NP is insufficient to form mtDNA

[Whole Genome Sequencing of Human mtDNA Based on Ion Torrent PGM™ Platform].

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Cao, Y; Zou, K N; Huang, J P; Ma, K; Ping, Y

2017-08-01

To analyze and detect the whole genome sequence of human mitochondrial DNA （mtDNA） by Ion Torrent PGM™ platform and to study the differences of mtDNA sequence in different tissues. Samples were collected from 6 unrelated individuals by forensic postmortem examination, including chest blood, hair, costicartilage, nail, skeletal muscle and oral epithelium. Amplification of whole genome sequence of mtDNA was performed by 4 pairs of primer. Libraries were constructed with Ion Shear™ Plus Reagents kit and Ion Plus Fragment Library kit. Whole genome sequencing of mtDNA was performed using Ion Torrent PGM™ platform. Sanger sequencing was used to determine the heteroplasmy positions and the mutation positions on HVⅠ region. The whole genome sequence of mtDNA from all samples were amplified successfully. Six unrelated individuals belonged to 6 different haplotypes. Different tissues in one individual had heteroplasmy difference. The heteroplasmy positions and the mutation positions on HVⅠ region were verified by Sanger sequencing. After a consistency check by the Kappa method, it was found that the results of mtDNA sequence had a high consistency in different tissues. The testing method used in present study for sequencing the whole genome sequence of human mtDNA can detect the heteroplasmy difference in different tissues, which have good consistency. The results provide guidance for the further applications of mtDNA in forensic science. Copyright© by the Editorial Department of Journal of Forensic Medicine

Estimates of Continental Ancestry Vary Widely among Individuals with the Same mtDNA Haplogroup

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Emery, Leslie S.; Magnaye, Kevin M.; Bigham, Abigail W.; Akey, Joshua M.; Bamshad, Michael J.

2015-01-01

The association between a geographical region and an mtDNA haplogroup(s) has provided the basis for using mtDNA haplogroups to infer an individual’s place of origin and genetic ancestry. Although it is well known that ancestry inferences using mtDNA haplogroups and those using genome-wide markers are frequently discrepant, little empirical information exists on the magnitude and scope of such discrepancies between multiple mtDNA haplogroups and worldwide populations. We compared genetic-ancestry inferences made by mtDNA-haplogroup membership to those made by autosomal SNPs in ∼940 samples of the Human Genome Diversity Panel and recently admixed populations from the 1000 Genomes Project. Continental-ancestry proportions often varied widely among individuals sharing the same mtDNA haplogroup. For only half of mtDNA haplogroups did the highest average continental-ancestry proportion match the highest continental-ancestry proportion of a majority of individuals with that haplogroup. Prediction of an individual’s mtDNA haplogroup from his or her continental-ancestry proportions was often incorrect. Collectively, these results indicate that for most individuals in the worldwide populations sampled, mtDNA-haplogroup membership provides limited information about either continental ancestry or continental region of origin. PMID:25620206

No variation and low synonymous substitution rates in coral mtDNA despite high nuclear variation

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Hellberg Michael E

2006-03-01

Full Text Available Abstract Background The mitochondrial DNA (mtDNA of most animals evolves more rapidly than nuclear DNA, and often shows higher levels of intraspecific polymorphism and population subdivision. The mtDNA of anthozoans (corals, sea fans, and their kin, by contrast, appears to evolve slowly. Slow mtDNA evolution has been reported for several anthozoans, however this slow pace has been difficult to put in phylogenetic context without parallel surveys of nuclear variation or calibrated rates of synonymous substitution that could permit quantitative rate comparisons across taxa. Here, I survey variation in the coding region of a mitochondrial gene from a coral species (Balanophyllia elegans known to possess high levels of nuclear gene variation, and estimate synonymous rates of mtDNA substitution by comparison to another coral (Tubastrea coccinea. Results The mtDNA surveyed (630 bp of cytochrome oxidase subunit I was invariant among individuals sampled from 18 populations spanning 3000 km of the range of B. elegans, despite high levels of variation and population subdivision for allozymes over these same populations. The synonymous substitution rate between B. elegans and T. coccinea (0.05%/site/106 years is similar to that in most plants, but 50–100 times lower than rates typical for most animals. In addition, while substitutions to mtDNA in most animals exhibit a strong bias toward transitions, mtDNA from these corals does not. Conclusion Slow rates of mitochondrial nucleotide substitution result in low levels of intraspecific mtDNA variation in corals, even when nuclear loci vary. Slow mtDNA evolution appears to be the basal condition among eukaryotes. mtDNA substitution rates switch from slow to fast abruptly and unidirectionally. This switch may stem from the loss of just one or a few mitochondrion-specific DNA repair or replication genes.

The congruence between matrilineal genetic (mtDNA) and geographic diversity of Iranians and the territorial populations

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Bahmanimehr, Ardeshir; Eskandari, Ghafar; Nikmanesh, Fatemeh

2015-01-01

Objective(s): From the ancient era, emergence of Agriculture in the connecting region of Mesopotamia and the Iranian plateau at the foothills of the Zagros Mountains, made Iranian gene pool as an important source of populating the region. It has differentiated the population spread and different language groups. In order to trace the maternal genetic affinity between Iranians and other populations of the area and to establish the place of Iranians in a broad framework of ethnically and linguistically diverse groups of Middle Eastern and South Asian populations, a comparative study of territorial groups was designed and used in the population statistical analysis. Materials and Methods: Mix of 616 samples was sequenced for complete mtDNA or hyper variable regions in this study. A published dataset of neighboring populations was used as a comparison in the Iranian matrilineal lineage study based on mtDNA haplogroups. Results: Statistical analyses data, demonstrate a close genetic structure of all Iranian populations, thus suggesting their origin from a common maternal ancestral gene pool and show that the diverse maternal genetic structure does not reflect population differentiation in the region in their language. Conclusion: In the aggregate of the eastward spreads of proto-Elamo-Dravidian language from the Southwest region of Iran, the Elam province, a reasonable degree of homogeneity has been observed among Iranians in this study. The approach will facilitate our perception of the more detailed relationship of the ethnic groups living in Iran with the other ancient peoples of the area, testing linguistic hypothesis and population movements. PMID:25810873

Some maternal lineages of domestic horses may have origins in East Asia revealed with further evidence of mitochondrial genomes and HVR-1 sequences

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Hongying Ma

2018-06-01

Full Text Available Objectives There are large populations of indigenous horse (Equus caballus in China and some other parts of East Asia. However, their matrilineal genetic diversity and origin remained poorly understood. Using a combination of mitochondrial DNA (mtDNA and hypervariable region (HVR-1 sequences, we aim to investigate the origin of matrilineal inheritance in these domestic horses. Methods To investigate patterns of matrilineal inheritance in domestic horses, we conducted a phylogenetic study using 31 de novo mtDNA genomes together with 317 others from the GenBank. In terms of the updated phylogeny, a total of 5,180 horse mitochondrial HVR-1 sequences were analyzed. Results Eightteen haplogroups (Aw-Rw were uncovered from the analysis of the whole mitochondrial genomes. Most of which have a divergence time before the earliest domestication of wild horses (about 5,800 years ago and during the Upper Paleolithic (35–10 KYA. The distribution of some haplogroups shows geographic patterns. The Lw haplogroup contained a significantly higher proportion of European horses than the horses from other regions, while haplogroups Jw, Rw, and some maternal lineages of Cw, have a higher frequency in the horses from East Asia. The 5,180 sequences of horse mitochondrial HVR-1 form nine major haplogroups (A-I. We revealed a corresponding relationship between the haplotypes of HVR-1 and those of whole mitochondrial DNA sequences. The data of the HVR-1 sequences also suggests that Jw, Rw, and some haplotypes of Cw may have originated in East Asia while Lw probably formed in Europe. Conclusions Our study supports the hypothesis of the multiple origins of the maternal lineage of domestic horses and some maternal lineages of domestic horses may have originated from East Asia.

Limited phylogeographic signal in sex-linked and autosomal loci despite geographically, ecologically, and phenotypically concordant structure of mtDNA variation in the Holarctic avian genus Eremophila.

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Sergei V Drovetski

Full Text Available Phylogeographic studies of Holarctic birds are challenging because they involve vast geographic scale, complex glacial history, extensive phenotypic variation, and heterogeneous taxonomic treatment across countries, all of which require large sample sizes. Knowledge about the quality of phylogeographic information provided by different loci is crucial for study design. We use sequences of one mtDNA gene, one sex-linked intron, and one autosomal intron to elucidate large scale phylogeographic patterns in the Holarctic lark genus Eremophila. The mtDNA ND2 gene identified six geographically, ecologically, and phenotypically concordant clades in the Palearctic that diverged in the Early-Middle Pleistocene and suggested paraphyly of the horned lark (E. alpestris with respect to the Temminck's lark (E. bilopha. In the Nearctic, ND2 identified five subclades which diverged in the Late Pleistocene. They overlapped geographically and were not concordant phenotypically or ecologically. Nuclear alleles provided little information on geographic structuring of genetic variation in horned larks beyond supporting the monophyly of Eremophila and paraphyly of the horned lark. Multilocus species trees based on two nuclear or all three loci provided poor support for haplogroups identified by mtDNA. The node ages calculated using mtDNA were consistent with the available paleontological data, whereas individual nuclear loci and multilocus species trees appeared to underestimate node ages. We argue that mtDNA is capable of discovering independent evolutionary units within avian taxa and can provide a reasonable phylogeographic hypothesis when geographic scale, geologic history, and phenotypic variation in the study system are too complex for proposing reasonable a priori hypotheses required for multilocus methods. Finally, we suggest splitting the currently recognized horned lark into five Palearctic and one Nearctic species.

Characterization of mtDNA haplogroups in 14 Mexican indigenous populations.

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Peñaloza-Espinosa, Rosenda I; Arenas-Aranda, Diego; Cerda-Flores, Ricardo M; Buentello-Malo, Leonor; González-Valencia, Gerardo; Torres, Javier; Alvarez, Berenice; Mendoza, Irma; Flores, Mario; Sandoval, Lucila; Loeza, Francisco; Ramos, Irma; Muñoz, Leopoldo; Salamanca, Fabio

2007-06-01

In this descriptive study we investigated the genetic structure of 513 Mexican indigenous subjects grouped in 14 populations (Mixteca-Alta, Mixteca-Baja, Otomi, Purépecha, Tzeltal, Tarahumara, Huichol, Nahua-Atocpan, Nahua-Xochimilco, Nahua-Zitlala, Nahua-Chilacachapa, Nahua-Ixhuatlancillo, Nahua-Necoxtla, and Nahua-Coyolillo) based on mtDNA haplogroups. These communities are geographically and culturally isolated; parents and grandparents were born in the community. Our data show that 98.6% of the mtDNA was distributed in haplogroups A1, A2, B1, B2, C1, C2, D1, and D2. Haplotype X6 was present in the Tarahumara (1/53) and Huichol (3/15), and haplotype L was present in the Nahua-Coyolillo (3/38). The first two principal components accounted for 95.9% of the total variation in the sample. The mtDNA haplogroup frequencies in the Purépecha and Zitlala were intermediate to cluster 1 (Otomi, Nahua-Ixhuatlancillo, Nahua-Xochimilco, Mixteca-Baja, and Tzeltal) and cluster 2 (Nahua-Necoxtla, Nahua-Atocpan, and Nahua-Chilacachapa). The Huichol, Tarahumara, Mixteca-Alta, and Nahua-Coyolillo were separated from the rest of the populations. According to these findings, the distribution of mtDNA haplogroups found in Mexican indigenous groups is similar to other Amerindian haplogroups, except for the African haplogroup found in one population.

DNA methyltransferase 1 mutations and mitochondrial pathology: is mtDNA methylated?

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Alessandra eMaresca

2015-03-01

Full Text Available Autosomal dominant cerebellar ataxia, deafness and narcolepsy (ADCA-DN and Hereditary sensory neuropathy with dementia and hearing loss (HSN1E are two rare, overlapping neurodegenerative syndromes that have been recently linked to allelic dominant pathogenic mutations in the DNMT1 gene, coding for DNA (cytosine-5-methyltransferase 1. DNMT1 is the enzyme responsible for maintaining the nuclear genome methylation patterns during the DNA replication and repair, thus regulating gene expression. The mutations responsible for ADCA-DN and HSN1E affect the replication foci targeting sequence domain, which regulates DNMT1 binding to chromatin. DNMT1 dysfunction is anticipated to lead to a global alteration of the DNA methylation pattern with predictable downstream consequences on gene expression. Interestingly, ADCA-DN and HSN1E phenotypes share some clinical features typical of mitochondrial diseases, such as optic atrophy, peripheral neuropathy and deafness, and some biochemical evidence of mitochondrial dysfunction. The recent discovery of a mitochondrial isoform of DNMT1 and its proposed role in methylating mitochondrial DNA (mtDNA suggests that DNMT1 mutations may directly affect mtDNA and mitochondrial physiology. On the basis of this latter finding the link between DNMT1 abnormal activity and mitochondrial dysfunction in ADCA-DN and HSN1E appears intuitive, however mtDNA methylation remains highly debated. In the last years several groups demonstrated the presence of 5-methylcytosine in mtDNA by different approaches, but, on the other end, the opposite evidence that mtDNA is not methylated has also been published. Since over 1500 mitochondrial proteins are encoded by the nuclear genome, the altered methylation of these genes may well have a critical role in leading to the mitochondrial impairment observed in ADCA-DN and HSN1E. Thus, many open questions still remain unanswered, such as why mtDNA should be methylated, and how this process is

mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese

International Nuclear Information System (INIS)

Wang Chengye; Kong Qingpeng; Yao Yonggang; Zhang Yaping

2006-01-01

Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL

Alterations in mtDNA, gastric carcinogenesis and early diagnosis.

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Rodrigues-Antunes, S; Borges, B N

2018-05-26

Gastric cancer remains one of the most prevalent cancers in the world. Due to this, efforts are being made to improve the diagnosis of this neoplasm and the search for molecular markers that may be involved in its genesis. Within this perspective, the mitochondrial DNA is considered as a potential candidate, since it has several well documented changes and is readily accessible. However, numerous alterations have been reported in mtDNA, not facilitating the visualization of which alterations and molecular markers are truly involved with gastric carcinogenesis. This review presents a compilation of the main known changes relating mtDNA to gastric cancer and their clinical significance.

mtDNA point and length heteroplasmy in high- and low radiation areas of Kerala

International Nuclear Information System (INIS)

Forster, L.; Forster, P.; Gurney, S.M.; Spencer, M.; Huang, C.; Röhl, A.; Brinkmann, B.

2010-01-01

A coastal peninsula in Kerala (India) contains the world's highest level of natural radioactivity in a densely populated area, offering an opportunity to characterize radiation-associated DNA mutations. Here, we focus on mitochondrial DNA (mtDNA) mutations, which are passed exclusively from the mother to her children. To analyse point mutations, we sampled 248 pedigrees (988 individuals) in the high-radiation peninsula and in nearby low-radiation islands as a control population. Then, in an extended sample of 1,172 mtDNA sequences (containing some non-Indians for comparison), we also analysed length mutations, which in mtDNA can lead to the phenomenon of length heteroplasmy, i.e. the existence of different DNA types in the same cell. We wished to find out how fast mtDNA mutates between generations, and whether the mutation rate is increased in radioactive conditions compared to the low-irradiation sample

Mitochondrial DNA (mtDNA haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

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Juan J. Yunis

2013-01-01

Full Text Available The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest.

Phylogeography, genetic diversity and demographic history of the ...

Indian Academy of Sciences (India)

Our data indicated that most of the Kurds mtDNA lineages belong to branches of the haplogroups with the Western Eurasian origin; with small fractions of the Eastern Eurasian and sub-Saharan African lineages. The low level of mtDNA diversity observed in the Havrami group presented a bias towards isolation or increased ...

A defect in the thymidine kinase 2 gene causing isolated mitochondrial myopathy without mtDNA depletion.

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Leshinsky-Silver, E; Michelson, M; Cohen, S; Ginsberg, M; Sadeh, M; Barash, V; Lerman-Sagie, T; Lev, D

2008-07-01

Isolated mitochondrial myopathies (IMM) are either due to primary defects in mtDNA, in nuclear genes that control mtDNA abundance and structure such as thymidine kinase 2 (TK2), or due to CoQ deficiency. Defects in the TK2 gene have been found to be associated with mtDNA depletion attributed to a depleted mitochondrial dNTP pool in non-dividing cells. We report an unusual case of IMM, homozygous for the H90N mutation in the TK2 gene but unlike other cases with the same mutation, does not demonstrate mtDNA depletion. The patient's clinical course is relatively mild and a muscle biopsy showed ragged red muscle fibers with a mild decrease in complexes I and an increase in complexes IV and II activities. This report extends the phenotypic expression of TK2 defects and suggests that all patients who present with an IMM even with normal quantities of mtDNA should be screened for TK2 mutations.

A Phenotype-Driven Approach to Generate Mouse Models with Pathogenic mtDNA Mutations Causing Mitochondrial Disease

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Johanna H.K. Kauppila

2016-09-01

Full Text Available Mutations of mtDNA are an important cause of human disease, but few animal models exist. Because mammalian mitochondria cannot be transfected, the development of mice with pathogenic mtDNA mutations has been challenging, and the main strategy has therefore been to introduce mutations found in cell lines into mouse embryos. Here, we describe a phenotype-driven strategy that is based on detecting clonal expansion of pathogenic mtDNA mutations in colonic crypts of founder mice derived from heterozygous mtDNA mutator mice. As proof of concept, we report the generation of a mouse line transmitting a heteroplasmic pathogenic mutation in the alanine tRNA gene of mtDNA displaying typical characteristics of classic mitochondrial disease. In summary, we describe a straightforward and technically simple strategy based on mouse breeding and histology to generate animal models of mtDNA-mutation disease, which will be of great importance for studies of disease pathophysiology and preclinical treatment trials.

Quantifying Selective Pressures Driving Bacterial Evolution Using Lineage Analysis

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Lambert, Guillaume; Kussell, Edo

2015-01-01

Organisms use a variety of strategies to adapt to their environments and maximize long-term growth potential, but quantitative characterization of the benefits conferred by the use of such strategies, as well as their impact on the whole population's rate of growth, remains challenging. Here, we use a path-integral framework that describes how selection acts on lineages—i.e., the life histories of individuals and their ancestors—to demonstrate that lineage-based measurements can be used to quantify the selective pressures acting on a population. We apply this analysis to Escherichia coli bacteria exposed to cyclical treatments of carbenicillin, an antibiotic that interferes with cell-wall synthesis and affects cells in an age-dependent manner. While the extensive characterization of the life history of thousands of cells is necessary to accurately extract the age-dependent selective pressures caused by carbenicillin, the same measurement can be recapitulated using lineage-based statistics of a single surviving cell. Population-wide evolutionary pressures can be extracted from the properties of the surviving lineages within a population, providing an alternative and efficient procedure to quantify the evolutionary forces acting on a population. Importantly, this approach is not limited to age-dependent selection, and the framework can be generalized to detect signatures of other trait-specific selection using lineage-based measurements. Our results establish a powerful way to study the evolutionary dynamics of life under selection and may be broadly useful in elucidating selective pressures driving the emergence of antibiotic resistance and the evolution of survival strategies in biological systems.

Migration and interaction in a contact zone: mtDNA variation among Bantu-speakers in Southern Africa.

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Chiara Barbieri

Full Text Available Bantu speech communities expanded over large parts of sub-Saharan Africa within the last 4000-5000 years, reaching different parts of southern Africa 1200-2000 years ago. The Bantu languages subdivide in several major branches, with languages belonging to the Eastern and Western Bantu branches spreading over large parts of Central, Eastern, and Southern Africa. There is still debate whether this linguistic divide is correlated with a genetic distinction between Eastern and Western Bantu speakers. During their expansion, Bantu speakers would have come into contact with diverse local populations, such as the Khoisan hunter-gatherers and pastoralists of southern Africa, with whom they may have intermarried. In this study, we analyze complete mtDNA genome sequences from over 900 Bantu-speaking individuals from Angola, Zambia, Namibia, and Botswana to investigate the demographic processes at play during the last stages of the Bantu expansion. Our results show that most of these Bantu-speaking populations are genetically very homogenous, with no genetic division between speakers of Eastern and Western Bantu languages. Most of the mtDNA diversity in our dataset is due to different degrees of admixture with autochthonous populations. Only the pastoralist Himba and Herero stand out due to high frequencies of particular L3f and L3d lineages; the latter are also found in the neighboring Damara, who speak a Khoisan language and were foragers and small-stock herders. In contrast, the close cultural and linguistic relatives of the Herero and Himba, the Kuvale, are genetically similar to other Bantu-speakers. Nevertheless, as demonstrated by resampling tests, the genetic divergence of Herero, Himba, and Kuvale is compatible with a common shared ancestry with high levels of drift, while the similarity of the Herero, Himba, and Damara probably reflects admixture, as also suggested by linguistic analyses.

Admixture of Eastern and Western European Red Deer Lineages as a Result of Postglacial Recolonization of the Czech Republic (Central Europe).

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Krojerová-Prokešová, Jarmila; Barančeková, Miroslava; Koubek, Petr

2015-01-01

Due to a restriction of the distributional range of European red deer (Cervus elaphus L.) during the Quaternary and subsequent recolonization of Europe from different refugia, a clear phylogeographical pattern in genetic structure has been revealed using mitochondrial DNA markers. In Central Europe, 2 distinct, eastern and western, lineages of European red deer are present; however, admixture between them has not yet been studied in detail. We used mitochondrial DNA (control region and cytochrome b gene) sequences and 22 microsatellite loci from 522 individuals to investigate the genetic diversity of red deer in what might be expected to be an intermediate zone. We discovered a high number of unique mtDNA haplotypes belonging to each lineage and high levels of genetic diversity (cyt b H = 0.867, D-loop H = 0.914). The same structuring of red deer populations was also revealed by microsatellite analysis, with results from both analyses thus suggesting a suture zone between the 2 lineages. Despite the fact that postglacial recolonization of Central Europe by red deer occurred more than 10000 years ago, the degree of admixture between the 2 lineages is relatively small, with only 10.8% admixed individuals detected. Direct translocations of animals by humans have slightly blurred the pattern in this region; however, this blurring was more apparent when using maternally inherited markers than nuclear markers. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Infantile presentation of the mtDNA A3243G tRNA(Leu (UUR)) mutation.

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Okhuijsen-Kroes, E.J.; Trijbels, J.M.F.; Sengers, R.C.A.; Mariman, E.C.M.; Heuvel, L.P.W.J. van den; Wendel, U.A.H.; Koch, G.; Smeitink, J.A.M.

2001-01-01

Mitochondrial DNA (mtDNA) disorders are clinically very heterogeneous, ranging from single organ involvement to severe multisystem disease. One of the most frequently observed mtDNA mutations is the A-to-G transition at position 3243 of the tRNA(Leu (UUR)) gene. This mutation is often related to

Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect β-oxidation.

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Xiaoshan Zhou

Full Text Available Thymidine kinase 2 (TK2 deficiency in humans causes mitochondrial DNA (mtDNA depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/- that progressively loses its mtDNA. The TK2(-/- mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/- mouse model to clarify the pathological role of progressive mtDNA depletion in liver for the severe outcome of TK2 deficiency. We observed that a gradual depletion of mtDNA in the liver of the TK2(-/- mice was accompanied by increasingly hypertrophic mitochondria and accumulation of fat vesicles in the liver cells. The levels of cholesterol and nonesterified fatty acids were elevated and there was accumulation of long chain acylcarnitines in plasma of the TK2(-/- mice. In mice with hepatic mtDNA levels below 20%, the blood sugar and the ketone levels dropped. These mice also exhibited reduced mitochondrial β-oxidation due to decreased transport of long chain acylcarnitines into the mitochondria. The gradual loss of mtDNA in the liver of the TK2(-/- mice causes impaired mitochondrial function that leads to defect β-oxidation and, as a result, insufficient production of ketone bodies and glucose. This study provides insight into the mechanism of encephalomyopathy caused by TK2 deficiency-induced mtDNA depletion that may be used to explore novel therapeutic strategies.

Thymidine kinase 2 deficiency-induced mtDNA depletion in mouse liver leads to defect β-oxidation.

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Zhou, Xiaoshan; Kannisto, Kristina; Curbo, Sophie; von Döbeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

2013-01-01

Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/-)) that progressively loses its mtDNA. The TK2(-/-) mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/-) mouse model to clarify the pathological role of progressive mtDNA depletion in liver for the severe outcome of TK2 deficiency. We observed that a gradual depletion of mtDNA in the liver of the TK2(-/-) mice was accompanied by increasingly hypertrophic mitochondria and accumulation of fat vesicles in the liver cells. The levels of cholesterol and nonesterified fatty acids were elevated and there was accumulation of long chain acylcarnitines in plasma of the TK2(-/-) mice. In mice with hepatic mtDNA levels below 20%, the blood sugar and the ketone levels dropped. These mice also exhibited reduced mitochondrial β-oxidation due to decreased transport of long chain acylcarnitines into the mitochondria. The gradual loss of mtDNA in the liver of the TK2(-/-) mice causes impaired mitochondrial function that leads to defect β-oxidation and, as a result, insufficient production of ketone bodies and glucose. This study provides insight into the mechanism of encephalomyopathy caused by TK2 deficiency-induced mtDNA depletion that may be used to explore novel therapeutic strategies.

Mitochondrial mosaics in the liver of 3 infants with mtDNA defects

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Scalais Emmanuel

2009-06-01

Full Text Available Abstract Background In muscle cytochrome oxidase (COX negative fibers (mitochondrial mosaics have often been visualized. Methods COX activity staining of liver for light and electron microscopy, muscle stains, blue native gel electrophoresis and activity assays of respiratory chain proteins, their immunolocalisation, mitochondrial and nuclear DNA analysis. Results Three unrelated infants showed a mitochondrial mosaic in the liver after staining for COX activity, i.e. hepatocytes with strongly reactive mitochondria were found adjacent to cells with many negative, or barely reactive, mitochondria. Deficiency was most severe in the patient diagnosed with Pearson syndrome. Ragged-red fibers were absent in muscle biopsies of all patients. Enzyme biochemistry was not diagnostic in muscle, fibroblasts and lymphocytes. Blue native gel electrophoresis of liver tissue, but not of muscle, demonstrated a decreased activity of complex IV; in both muscle and liver subcomplexes of complex V were seen. Immunocytochemistry of complex IV confirmed the mosaic pattern in two livers, but not in fibroblasts. MRI of the brain revealed severe white matter cavitation in the Pearson case, but only slight cortical atrophy in the Alpers-Huttenlocher patient, and a normal image in the 3rd. MtDNA in leucocytes showed a common deletion in 50% of the mtDNA molecules of the Pearson patient. In the patient diagnosed with Alpers-Huttenlocher syndrome, mtDNA was depleted for 60% in muscle. In the 3rd patient muscular and hepatic mtDNA was depleted for more than 70%. Mutations in the nuclear encoded gene of POLG were subsequently found in both the 2nd and 3rd patients. Conclusion Histoenzymatic COX staining of a liver biopsy is fast and yields crucial data about the pathogenesis; it indicates whether mtDNA should be assayed. Each time a mitochondrial disorder is suspected and muscle data are non-diagnostic, a liver biopsy should be recommended. Mosaics are probably more frequent

Updating phylogeny of mitochondrial DNA macrohaplogroup m in India: dispersal of modern human in South Asian corridor.

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Adimoolam Chandrasekar

2009-10-01

Full Text Available To construct maternal phylogeny and prehistoric dispersals of modern human being in the Indian sub continent, a diverse subset of 641 complete mitochondrial DNA (mtDNA genomes belonging to macrohaplogroup M was chosen from a total collection of 2,783 control-region sequences, sampled from 26 selected tribal populations of India. On the basis of complete mtDNA sequencing, we identified 12 new haplogroups--M53 to M64; redefined/ascertained and characterized haplogroups M2, M3, M4, M5, M6, M8'C'Z, M9, M10, M11, M12-G, D, M18, M30, M33, M35, M37, M38, M39, M40, M41, M43, M45 and M49, which were previously described by control and/or coding-region polymorphisms. Our results indicate that the mtDNA lineages reported in the present study (except East Asian lineages M8'C'Z, M9, M10, M11, M12-G, D are restricted to Indian region.The deep rooted lineages of macrohaplogroup 'M' suggest in-situ origin of these haplogroups in India. Most of these deep rooting lineages are represented by multiple ethnic/linguist groups of India. Hierarchical analysis of molecular variation (AMOVA shows substantial subdivisions among the tribes of India (Fst = 0.16164. The current Indian mtDNA gene pool was shaped by the initial settlers and was galvanized by minor events of gene flow from the east and west to the restricted zones. Northeast Indian mtDNA pool harbors region specific lineages, other Indian lineages and East Asian lineages. We also suggest the establishment of an East Asian gene in North East India through admixture rather than replacement.

Inspecting close maternal relatedness: Towards better mtDNA population samples in forensic databases.

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Bodner, Martin; Irwin, Jodi A; Coble, Michael D; Parson, Walther

2011-03-01

Reliable data are crucial for all research fields applying mitochondrial DNA (mtDNA) as a genetic marker. Quality control measures have been introduced to ensure the highest standards in sequence data generation, validation and a posteriori inspection. A phylogenetic alignment strategy has been widely accepted as a prerequisite for data comparability and database searches, for forensic applications, for reconstructions of human migrations and for correct interpretation of mtDNA mutations in medical genetics. There is continuing effort to enhance the number of worldwide population samples in order to contribute to a better understanding of human mtDNA variation. This has often lead to the analysis of convenience samples collected for other purposes, which might not meet the quality requirement of random sampling for mtDNA data sets. Here, we introduce an additional quality control means that deals with one aspect of this limitation: by combining autosomal short tandem repeat (STR) marker with mtDNA information, it helps to avoid the bias introduced by related individuals included in the same (small) sample. By STR analysis of individuals sharing their mitochondrial haplotype, pedigree construction and subsequent software-assisted calculation of likelihood ratios based on the allele frequencies found in the population, closely maternally related individuals can be identified and excluded. We also discuss scenarios that allow related individuals in the same set. An ideal population sample would be representative for its population: this new approach represents another contribution towards this goal. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Canis mtDNA HV1 database: a web-based tool for collecting and surveying Canis mtDNA HV1 haplotype in public database.

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Thai, Quan Ke; Chung, Dung Anh; Tran, Hoang-Dung

2017-06-26

Canine and wolf mitochondrial DNA haplotypes, which can be used for forensic or phylogenetic analyses, have been defined in various schemes depending on the region analyzed. In recent studies, the 582 bp fragment of the HV1 region is most commonly used. 317 different canine HV1 haplotypes have been reported in the rapidly growing public database GenBank. These reported haplotypes contain several inconsistencies in their haplotype information. To overcome this issue, we have developed a Canis mtDNA HV1 database. This database collects data on the HV1 582 bp region in dog mitochondrial DNA from the GenBank to screen and correct the inconsistencies. It also supports users in detection of new novel mutation profiles and assignment of new haplotypes. The Canis mtDNA HV1 database (CHD) contains 5567 nucleotide entries originating from 15 subspecies in the species Canis lupus. Of these entries, 3646 were haplotypes and grouped into 804 distinct sequences. 319 sequences were recognized as previously assigned haplotypes, while the remaining 485 sequences had new mutation profiles and were marked as new haplotype candidates awaiting further analysis for haplotype assignment. Of the 3646 nucleotide entries, only 414 were annotated with correct haplotype information, while 3232 had insufficient or lacked haplotype information and were corrected or modified before storing in the CHD. The CHD can be accessed at http://chd.vnbiology.com . It provides sequences, haplotype information, and a web-based tool for mtDNA HV1 haplotyping. The CHD is updated monthly and supplies all data for download. The Canis mtDNA HV1 database contains information about canine mitochondrial DNA HV1 sequences with reconciled annotation. It serves as a tool for detection of inconsistencies in GenBank and helps identifying new HV1 haplotypes. Thus, it supports the scientific community in naming new HV1 haplotypes and to reconcile existing annotation of HV1 582 bp sequences.

Evidence of at least two evolutionary lineages in Melipona subnitida (Apidae, Meliponini) suggested by mtDNA variability and geometric morphometrics of forewings

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Bonatti, Vanessa; Simões, Zilá Luz Paulino; Franco, Fernando Faria; Francoy, Tiago Mauricio

2014-01-01

Melipona subnitida, a tropical stingless bee, is an endemic species of the Brazilian northeast and exhibits great potential for honey and pollen production in addition to its role as one of the main pollinators of the Caatinga biome. To understand the genetic structure and better assist in the conservation of this species, we characterized the population variability of M. subnitida using geometric morphometrics of the forewing and cytochrome c oxidase I gene fragment sequencing. We collected workers from six localities in the northernmost distribution. Both methodologies indicated that the variability among the sampled populations is related both to the environment in which samples were collected and the geographical distance between the sampling sites, indicating that differentiation among the populations is due to the existence of at least evolutionary lineages. Molecular clock data suggest that this differentiation may have begun in the middle Pleistocene, approximately 396 kya. The conservation of all evolutionary lineages is important since they can present differential resistance to environmental changes, as resistance to drought and diseases.

Evolutionary relationships in the sand-dwelling cichlid lineage of lake tanganyika suggest multiple colonization of rocky habitats and convergent origin of biparental mouthbrooding.

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Koblmüller, Stephan; Salzburger, Walter; Sturmbauer, Christian

2004-01-01

The cichlid species flock of Lake Tanganyika is comprised of seven seeding lineages that evolved in step with changes of the lake environment. One seeding lineage diversified into at least six lineages within a short period of time. Our study focuses on the diversification of one of these lineages, the Ectodini, comprising highly specialized, sand- and rock-dwelling species. They display two distinct breeding styles: maternal and biparental mouthbrooding. By analyzing three mtDNA gene segments in 30 species representing all 13 described genera, we show that the Ectodini rapidly diversified into four clades at the onset of their radiation. The monotypic genus Grammatotria is likely to represent the most ancestral split, followed by the almost contemporary origin of three additional clades, the first comprising the benthic genus Callochromis, the second comprising the benthic genera Asprotilapia, Xenotilapia, Enantiopus, and Microdontochromis, and the third comprising the semi-pelagic genera Ophthalmotilapia, Cardiopharynx, Cyathopharynx, Ectodus, Aulonocranus, Lestradea, and Cunningtonia. Our study confirms the benthic and sand-dwelling life-style as ancestral. Rocky habitats were colonized independently in the Xenotilapia- and Ophthalmotilapia-clade. The Xenotilapia-clade comprises both maternal and biparental mouthbrooders. Their mode of breeding appears to be highly plastic: biparental mouthbrooding either evolved once in the common ancestor of the clade, to be reverted at least three times, or evolved at least five times independently from a maternally mouthbrooding ancestor. Furthermore, the genera Xenotilapia, Microdontochromis, Lestradea, and Ophthalmotilapia appeared paraphyletic in our analyses, suggesting the need of taxonomic revision.

Identification of West Eurasian mitochondrial haplogroups by mtDNA SNP screening: results of the 2006-2007 EDNAP collaborative exercise

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Parson, Walther; Fendt, Liane; Ballard, David

2008-01-01

no previous experience with the technology and/or mtDNA analysis. The results of this collaborative exercise stimulate the expansion of screening methods in forensic laboratories to increase efficiency and performance of mtDNA typing, and thus demonstrates that mtDNA SNP typing is a powerful tool for forensic......The European DNA Profiling (EDNAP) Group performed a collaborative exercise on a mitochondrial (mt) DNA screening assay that targeted 16 nucleotide positions in the coding region and allowed for the discrimination of major west Eurasian mtDNA haplogroups. The purpose of the exercise was to evaluate...

Detection of sister-species in invasive populations of the fall armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) from Uganda

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Tay, Wee Tek; Walsh, Thomas K.; Kanyesigye, Dalton; Adumo, Stella; Abongosi, Joseph; Ochen, Stephen; Sserumaga, Julius; Alibu, Simon; Abalo, Grace; Asea, Godfrey; Agona, Ambrose

2018-01-01

The fall armyworm (FAW) Spodoptera frugiperda (J. E. Smith) is a species native to the Americas. This polyphagous lepidopteran pest was first reported in Nigeria and the Democratic Republic of São Tomé and Principe in 2016, but its presence in eastern Africa has not been confirmed via molecular characterisation. In this study, FAW specimens from western and central Uganda were identified based on the partial mtDNA COI gene sequences, with mtDNA COI haplotypes matching those identified in Nigeria and São Tomé. In this study, we sequence an additional partial mtDNA Cyt b gene and also the partial mtDNA COIII gene in Ugandan FAW samples. We detected identical mitochondrial DNA haplotypes for both the mtDNA Cyt b and COI partial genes, while combining the mtDNA COI/Cyt b haplotypes and mtDNA COIII haplotypes enabled a new maternal lineage in the Ugandan corn-preferred FAW samples to be identified. Our results suggested that the African incursions of S. frugiperda involved at least three maternal lineages. Recent full genome, phylogenetic and microsatellite analyses provided evidence to support S. frugiperda as likely consisted of two sympatric sister species known as the corn-preferred and rice-preferred strains. In our Ugandan FAW populations, we identified the presence of mtDNA haplotypes representative of both sister species. It is not known if both FAW sister species were originally introduced together or separately, and whether they have since spread as a single population. Further analyses of additional specimens originally collected from São Tomé, Nigeria and throughout Africa would be required to clarify this issue. Importantly, our finding showed that the genetic diversity of the African corn-preferred FAW species is higher than previously reported. This potentially contributed to the success of FAW establishment in Africa. Furthermore, with the additional maternal lineages detected, there is likely an increase in paternal lineages, thereby increasing

The Mechanism for Type I Interferon Induction by Mycobacterium tuberculosis is Bacterial Strain-Dependent.

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Kirsten E Wiens

2016-08-01

Full Text Available Type I interferons (including IFNαβ are innate cytokines that may contribute to pathogenesis during Mycobacterium tuberculosis (Mtb infection. To induce IFNβ, Mtb must gain access to the host cytosol and trigger stimulator of interferon genes (STING signaling. A recently proposed model suggests that Mtb triggers STING signaling through bacterial DNA binding cyclic GMP-AMP synthase (cGAS in the cytosol. The aim of this study was to test the generalizability of this model using phylogenetically distinct strains of the Mtb complex (MTBC. We infected bone marrow derived macrophages with strains from MTBC Lineages 2, 4 and 6. We found that the Lineage 6 strain induced less IFNβ, and that the Lineage 2 strain induced more IFNβ, than the Lineage 4 strain. The strains did not differ in their access to the host cytosol and IFNβ induction by each strain required both STING and cGAS. We also found that the three strains shed similar amounts of bacterial DNA. Interestingly, we found that the Lineage 6 strain was associated with less mitochondrial stress and less mitochondrial DNA (mtDNA in the cytosol compared with the Lineage 4 strain. Treating macrophages with a mitochondria-specific antioxidant reduced cytosolic mtDNA and inhibited IFNβ induction by the Lineage 2 and 4 strains. We also found that the Lineage 2 strain did not induce more mitochondrial stress than the Lineage 4 strain, suggesting that additional pathways contribute to higher IFNβ induction. These results indicate that the mechanism for IFNβ by Mtb is more complex than the established model suggests. We show that mitochondrial dynamics and mtDNA contribute to IFNβ induction by Mtb. Moreover, we show that the contribution of mtDNA to the IFNβ response varies by MTBC strain and that additional mechanisms exist for Mtb to induce IFNβ.

Therapeutic Targeting of the Mitochondria Initiates Excessive Superoxide Production and Mitochondrial Depolarization Causing Decreased mtDNA Integrity.

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Pokrzywinski, Kaytee L; Biel, Thomas G; Kryndushkin, Dmitry; Rao, V Ashutosh

2016-01-01

Mitochondrial dysregulation is closely associated with excessive reactive oxygen species (ROS) production. Altered redox homeostasis has been implicated in the onset of several diseases including cancer. Mitochondrial DNA (mtDNA) and proteins are particularly sensitive to ROS as they are in close proximity to the respiratory chain (RC). Mitoquinone (MitoQ), a mitochondria-targeted redox agent, selectively damages breast cancer cells possibly through damage induced via enhanced ROS production. However, the effects of MitoQ and other triphenylphosphonium (TPP+) conjugated agents on cancer mitochondrial homeostasis remain unknown. The primary objective of this study was to determine the impact of mitochondria-targeted agent [(MTAs) conjugated to TPP+: mitoTEMPOL, mitoquinone and mitochromanol-acetate] on mitochondrial physiology and mtDNA integrity in breast (MDA-MB-231) and lung (H23) cancer cells. The integrity of the mtDNA was assessed by quantifying the degree of mtDNA fragmentation and copy number, as well as by measuring mitochondrial proteins essential to mtDNA stability and maintenance (TFAM, SSBP1, TWINKLE, POLG and POLRMT). Mitochondrial status was evaluated by measuring superoxide production, mitochondrial membrane depolarization, oxygen consumption, extracellular acidification and mRNA or protein levels of the RC complexes along with TCA cycle activity. In this study, we demonstrated that all investigated MTAs impair mitochondrial health and decrease mtDNA integrity in MDA-MB-231 and H23 cells. However, differences in the degree of mitochondrial damage and mtDNA degradation suggest unique properties among each MTA that may be cell line, dose and time dependent. Collectively, our study indicates the potential for TPP+ conjugated molecules to impair breast and lung cancer cells by targeting mitochondrial homeostasis.

Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice

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Safdar, Adeel; Bourgeois, Jacqueline M.; Ogborn, Daniel I.; Little, Jonathan P.; Hettinga, Bart P.; Akhtar, Mahmood; Thompson, James E.; Melov, Simon; Mocellin, Nicholas J.; Kujoth, Gregory C.; Prolla, Tomas A.; Tarnopolsky, Mark A.

2011-01-01

A causal role for mitochondrial DNA (mtDNA) mutagenesis in mammalian aging is supported by recent studies demonstrating that the mtDNA mutator mouse, harboring a defect in the proofreading-exonuclease activity of mitochondrial polymerase gamma, exhibits accelerated aging phenotypes characteristic of human aging, systemic mitochondrial dysfunction, multisystem pathology, and reduced lifespan. Epidemiologic studies in humans have demonstrated that endurance training reduces the risk of chronic diseases and extends life expectancy. Whether endurance exercise can attenuate the cumulative systemic decline observed in aging remains elusive. Here we show that 5 mo of endurance exercise induced systemic mitochondrial biogenesis, prevented mtDNA depletion and mutations, increased mitochondrial oxidative capacity and respiratory chain assembly, restored mitochondrial morphology, and blunted pathological levels of apoptosis in multiple tissues of mtDNA mutator mice. These adaptations conferred complete phenotypic protection, reduced multisystem pathology, and prevented premature mortality in these mice. The systemic mitochondrial rejuvenation through endurance exercise promises to be an effective therapeutic approach to mitigating mitochondrial dysfunction in aging and related comorbidities. PMID:21368114

Effects of a sex-ratio distorting endosymbiont on mtDNA variation in a global insect pest

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Cook James M

2009-03-01

Full Text Available Abstract Background Patterns of mtDNA variation within a species reflect long-term population structure, but may also be influenced by maternally inherited endosymbionts, such as Wolbachia. These bacteria often alter host reproductive biology and can drive particular mtDNA haplotypes through populations. We investigated the impacts of Wolbachia infection and geography on mtDNA variation in the diamondback moth, a major global pest whose geographic distribution reflects both natural processes and transport via human agricultural activities. Results The mtDNA phylogeny of 95 individuals sampled from 10 countries on four continents revealed two major clades. One contained only Wolbachia-infected individuals from Malaysia and Kenya, while the other contained only uninfected individuals, from all countries including Malaysia and Kenya. Within the uninfected group was a further clade containing all individuals from Australasia and displaying very limited sequence variation. In contrast, a biparental nuclear gene phylogeny did not have infected and uninfected clades, supporting the notion that maternally-inherited Wolbachia are responsible for the mtDNA pattern. Only about 5% (15/306 of our global sample of individuals was infected with the plutWB1 isolate and even within infected local populations, many insects were uninfected. Comparisons of infected and uninfected isofemale lines revealed that plutWB1 is associated with sex ratio distortion. Uninfected lines have a 1:1 sex ratio, while infected ones show a 2:1 female bias. Conclusion The main correlate of mtDNA variation in P. xylostella is presence or absence of the plutWB1 infection. This is associated with substantial sex ratio distortion and the underlying mechanisms deserve further study. In contrast, geographic origin is a poor predictor of moth mtDNA sequences, reflecting human activity in moving the insects around the globe. The exception is a clade of Australasian individuals, which may

MtDNA T4216C variation in multiple sclerosis

DEFF Research Database (Denmark)

Andalib, Sasan; Emamhadi, Mohammadreza; Yousefzadeh-Chabok, Shahrokh

2016-01-01

MtDNA T4216C variation has frequently been investigated in Multiple Sclerosis (MS) patients; nonetheless, controversy has existed about the evidence of association of this variation with susceptibility to MS. The present systematic review and meta-analysis converge the results of the preceding pu...

MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

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Stumpf, Jeffrey D; Copeland, William C

2014-10-01

Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

The origin of widespread species in a poor dispersing lineage (diving beetle genus Deronectes

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David García-Vázquez

2016-09-01

Full Text Available In most lineages, most species have restricted geographic ranges, with only few reaching widespread distributions. How these widespread species reached their current ranges is an intriguing biogeographic and evolutionary question, especially in groups known to be poor dispersers. We reconstructed the biogeographic and temporal origin of the widespread species in a lineage with particularly poor dispersal capabilities, the diving beetle genus Deronectes (Dytiscidae. Most of the ca. 60 described species of Deronectes have narrow ranges in the Mediterranean area, with only four species with widespread European distributions. We sequenced four mitochondrial and two nuclear genes of 297 specimens of 109 different populations covering the entire distribution of the four lineages of Deronectes, including widespread species. Using Bayesian probabilities with an a priori evolutionary rate, we performed (1 a global phylogeny/phylogeography to estimate the relationships of the main lineages within each group and root them, and (2 demographic analyses of the best population coalescent model for each species group, including a reconstruction of the geographical history estimated from the distribution of the sampled localities. We also selected 56 specimens to test for the presence of Wolbachia, a maternally transmitted parasite that can alter the patterns of mtDNA variability. All species of the four studied groups originated in the southern Mediterranean peninsulas and were estimated to be of Pleistocene origin. In three of the four widespread species, the central and northern European populations were nested within those in the northern areas of the Anatolian, Balkan and Iberian peninsulas respectively, suggesting a range expansion at the edge of the southern refugia. In the Mediterranean peninsulas the widespread European species were replaced by vicariant taxa of recent origin. The fourth species (D. moestus was proven to be a composite of unrecognised

mtDNA copy number in oocytes of different sizes from individual pre- and post-pubertal pigs

DEFF Research Database (Denmark)

Pedersen, Hanne Skovsgaard; Løvendahl, Peter; Larsen, Knud Erik

2014-01-01

from ovaries of 10 pre- and 10 post-pubertal pigs. Cumulus cells were removed and the oocytes were measured (inside-ZP-diameter). Oocytes were transferred to DNAase-free tubes, snap-frozen, and stored at –80°C. The genes ND1 and COX1 were used to determine the mtDNA copy number. Plasmid preparations...... Reproduction 131, 233–245). However, the correlation between size and mtDNA copy number in single oocytes has not been determined. This study describes the relation between oocytes of defined diameters from individual pre- and postpubertal pigs and mtDNA copy number. Cumulus-oocyte complexes were aspirated...

Influence of geology and human activity on the genetic structure and demography of the Oriental fire-bellied toad (Bombina orientalis).

Science.gov (United States)

Fong, Jonathan J; Li, Pi-Peng; Yang, Bao-Tian; Zhou, Zheng-Yan; Leaché, Adam D; Min, Mi-Sook; Waldman, Bruce

2016-04-01

The Oriental fire-bellied toad (Bombina orientalis) is a commonly used study organism, but knowledge of its evolutionary history is incomplete. We analyze sequence data from four genetic markers (mtDNA genes encoding cytochrome c oxidase subunit I, cytochrome b, and 12S-16S rRNA; nuDNA gene encoding recombination activating gene 2) from 188 individuals across its range in Northeast Asia to elucidate phylogeographic patterns and to identify the historic events that shaped its evolutionary history. Although morphologically similar across its range, B. orientalis exhibits phylogeographic structure, which we infer was shaped by geologic, climatic, and anthropogenic events. Phylogenetic and divergence-dating analyses recover four genetically distinct groups of B. orientalis: Lineage 1-Shandong Province and Beijing (China); Lineage 2-Bukhan Mountain (Korea); Lineage 3-Russia, Northeast China, and northern South Korea; and Lineage 4-South Korea. Lineage 2 was previously unknown. Additionally, we discover an area of secondary contact on the Korean Peninsula, and infer a single dispersal event as the origin of the insular Jeju population. Skyline plots estimate different population histories for the four lineages: Lineages 1 and 2 experienced population decreases, Lineage 3 remained stable, while Lineage 4 experienced a sharp increase during the Holocene. The timing of the population expansion of Lineage 4 coincides with the advent of rice cultivation, which may have facilitated the increase in population size by providing additional breeding habitat. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic surfing, not allopatric divergence, explains spatial sorting of mitochondrial haplotypes in venomous coralsnakes.

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Streicher, Jeffrey W; McEntee, Jay P; Drzich, Laura C; Card, Daren C; Schield, Drew R; Smart, Utpal; Parkinson, Christopher L; Jezkova, Tereza; Smith, Eric N; Castoe, Todd A

2016-07-01

Strong spatial sorting of genetic variation in contiguous populations is often explained by local adaptation or secondary contact following allopatric divergence. A third explanation, spatial sorting by stochastic effects of range expansion, has been considered less often though theoretical models suggest it should be widespread, if ephemeral. In a study designed to delimit species within a clade of venomous coralsnakes, we identified an unusual pattern within the Texas coral snake (Micrurus tener): strong spatial sorting of divergent mitochondrial (mtDNA) lineages over a portion of its range, but weak sorting of these lineages elsewhere. We tested three alternative hypotheses to explain this pattern-local adaptation, secondary contact following allopatric divergence, and range expansion. Collectively, near panmixia of nuclear DNA, the signal of range expansion associated sampling drift, expansion origins in the Gulf Coast of Mexico, and species distribution modeling suggest that the spatial sorting of divergent mtDNA lineages within M. tener has resulted from genetic surfing of standing mtDNA variation-not local adaptation or allopatric divergence. Our findings highlight the potential for the stochastic effects of recent range expansion to mislead estimations of population divergence made from mtDNA, which may be exacerbated in systems with low vagility, ancestral mtDNA polymorphism, and male-biased dispersal. © 2016 The Author(s).

Maternal DNA lineages at the gate of Europe in the 10th century AD

Science.gov (United States)

Modi, Alessandra; Vai, Stefania; Pilli, Elena; Mircea, Cristina; Radu, Claudia; Urduzia, Claudia; Pinter, Zeno Karl; Bodolică, Vitalie; Dobrinescu, Cătălin; Hervella, Montserrat; Popescu, Octavian; Lari, Martina; Caramelli, David; Kelemen, Beatrice

2018-01-01

Given the paucity of archaeogenetic data available for medieval European populations in comparison to other historical periods, the genetic landscape of this age appears as a puzzle of dispersed, small, known pieces. In particular, Southeastern Europe has been scarcely investigated to date. In this paper, we report the study of mitochondrial DNA in 10th century AD human samples from Capidava necropolis, located in Dobruja (Southeastern Romania, Southeastern Europe). This geographical region is particularly interesting because of the extensive population flux following diverse migration routes, and the complex interactions between distinct population groups during the medieval period. We successfully amplified and typed the mitochondrial control region of 10 individuals. For five of them, we also reconstructed the complete mitochondrial genomes using hybridization-based DNA capture combined with Next Generation Sequencing. We have portrayed the genetic structure of the Capidava medieval population, represented by 10 individuals displaying 8 haplotypes (U5a1c2a, V1a, R0a2’3, H1, U3a, N9a9, H5e1a1, and H13a1a3). Remarkable for this site is the presence of both Central Asiatic (N9a) and common European mtDNA haplotypes, establishing Capidava as a point of convergence between East and West. The distribution of mtDNA lineages in the necropolis highlighted the existence of two groups of two individuals with close maternal relationships as they share the same haplotypes. We also sketch, using comparative statistical and population genetic analyses, the genetic relationships between the investigated dataset and other medieval and modern Eurasian populations. PMID:29538439

SG-ADVISER mtDNA: a web server for mitochondrial DNA annotation with data from 200 samples of a healthy aging cohort.

Science.gov (United States)

Rueda, Manuel; Torkamani, Ali

2017-08-18

Whole genome and exome sequencing usually include reads containing mitochondrial DNA (mtDNA). Yet, state-of-the-art pipelines and services for human nuclear genome variant calling and annotation do not handle mitochondrial genome data appropriately. As a consequence, any researcher desiring to add mtDNA variant analysis to their investigations is forced to explore the literature for mtDNA pipelines, evaluate them, and implement their own instance of the desired tool. This task is far from trivial, and can be prohibitive for non-bioinformaticians. We have developed SG-ADVISER mtDNA, a web server to facilitate the analysis and interpretation of mtDNA genomic data coming from next generation sequencing (NGS) experiments. The server was built in the context of our SG-ADVISER framework and on top of the MtoolBox platform (Calabrese et al., Bioinformatics 30(21):3115-3117, 2014), and includes most of its functionalities (i.e., assembly of mitochondrial genomes, heteroplasmic fractions, haplogroup assignment, functional and prioritization analysis of mitochondrial variants) as well as a back-end and a front-end interface. The server has been tested with unpublished data from 200 individuals of a healthy aging cohort (Erikson et al., Cell 165(4):1002-1011, 2016) and their data is made publicly available here along with a preliminary analysis of the variants. We observed that individuals over ~90 years old carried low levels of heteroplasmic variants in their genomes. SG-ADVISER mtDNA is a fast and functional tool that allows for variant calling and annotation of human mtDNA data coming from NGS experiments. The server was built with simplicity in mind, and builds on our own experience in interpreting mtDNA variants in the context of sudden death and rare diseases. Our objective is to provide an interface for non-bioinformaticians aiming to acquire (or contrast) mtDNA annotations via MToolBox. SG-ADVISER web server is freely available to all users at https://genomics.scripps.edu/mtdna .

Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders.

Science.gov (United States)

Lorenz, Carmen; Lesimple, Pierre; Bukowiecki, Raul; Zink, Annika; Inak, Gizem; Mlody, Barbara; Singh, Manvendra; Semtner, Marcus; Mah, Nancy; Auré, Karine; Leong, Megan; Zabiegalov, Oleksandr; Lyras, Ekaterini-Maria; Pfiffer, Vanessa; Fauler, Beatrix; Eichhorst, Jenny; Wiesner, Burkhard; Huebner, Norbert; Priller, Josef; Mielke, Thorsten; Meierhofer, David; Izsvák, Zsuzsanna; Meier, Jochen C; Bouillaud, Frédéric; Adjaye, James; Schuelke, Markus; Wanker, Erich E; Lombès, Anne; Prigione, Alessandro

2017-05-04

Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation. NPCs derived in this way from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C) showed defective ATP production and abnormally high mitochondrial membrane potential (MMP), plus altered calcium homeostasis, which represents a potential cause of neural impairment. High-content screening of FDA-approved drugs using the MMP phenotype highlighted avanafil, which we found was able to partially rescue the calcium defect in patient NPCs and differentiated neurons. Overall, our results show that iPSC-derived NPCs provide an effective model for drug screening to target mtDNA disorders that affect the nervous system. Copyright © 2016 Elsevier Inc. All rights reserved.

Pliocene-Pleistocene lineage diversifications in the Eastern Indigo Snake (Drymarchon couperi) in the Southeastern United States.

Science.gov (United States)

Krysko, Kenneth L; Nuñez, Leroy P; Lippi, Catherine A; Smith, Daniel J; Granatosky, Michael C

2016-05-01

Indigo Snakes (Drymarchon; with five currently recognized species) occur from northern Argentina, northward to the United States in southern Texas and eastward in disjunct populations in Florida and Georgia. Based on this known allopatry and a difference in supralabial morphology the two United States taxa previously considered as subspecies within D. corais (Boie 1827), the Western Indigo Snake, D. melanurus erebennus (Cope 1860), and Eastern Indigo Snake, D. couperi (Holbrook 1842), are currently recognized as separate species. Drymarchon couperi is a Federally-designated Threatened species by the United States Fish and Wildlife Service under the Endangered Species Act, and currently being incorporated into a translocation program. This, combined with its disjunct distribution makes it a prime candidate for studying speciation and genetic divergence. In this study, we (1) test the hypothesis that D. m. erebennus and D. couperi are distinct lineages by analyzing 2411 base pairs (bp) of two mitochondrial (mtDNA) loci and one single copy nuclear (scnDNA) locus; (2) estimate the timing of speciation using a relaxed phylogenetics method to determine if Milankovitch cycles during the Pleistocene might have had an influence on lineage diversifications; (3) examine historical population demography to determine if identified lineages have undergone population declines, expansions, or remained stable during the most recent Milankovitch cycles; and (4) use this information to assist in an effective and scientifically sound translocation program. Our molecular data support the initial hypothesis that D. melanurus and D. couperi should be recognized as distinct species, but further illustrate that D. couperi is split into two distinct genetic lineages that correspond to historical biogeography and sea level changes in peninsular Florida. These two well-supported genetic lineages (herein termed Atlantic and Gulf lineages) illustrate a common biogeographic distributional break

Internucleotide correlations and nucleotide periodicity in Drosophila mtDNA: New evidence for panselective evolution

Directory of Open Access Journals (Sweden)

Carlos Y Valenzuela

2010-01-01

Full Text Available Analysis for the homogeneity of the distribution of the second base of dinucleotides in relation to the first, whose bases are separated by 0, 1, 2,... 21 nucleotide sites, was performed with the VIH-1 genome (cDNA, the Drosophila mtDNA, the Drosophila Torso gene and the human p-globin gene. These four DNA segments showed highly significant heterogeneities of base distributions that cannot be accounted for by neutral or nearly neutral evolution or by the "neighbor influence" of nucleotides on mutation rates. High correlations are found in the bases of dinucleotides separated by 0, 1 and more number of sites. A periodicity of three consecutive significance values (measured by the x²9 was found only in Drosophila mtDNA. This periodicity may be due to an unknown structure or organization of mtDNA. This non-random distribution of the two bases of dinucleotides widespread throughout these DNA segments is rather compatible with panselective evolution and generalized internucleotide co-adaptation.

Cytokine-Regulated GADD45G Induces Differentiation and Lineage Selection in Hematopoietic Stem Cells

Directory of Open Access Journals (Sweden)

Frederic B. Thalheimer

2014-07-01

Full Text Available The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicate balance requires further elucidation. We identified the tumor suppressor GADD45G as an instructor of LT-HSC differentiation under the control of differentiation-promoting cytokine receptor signaling. GADD45G immediately induces and accelerates differentiation in LT-HSCs and overrides the self-renewal program by specifically activating MAP3K4-mediated MAPK p38. Conversely, the absence of GADD45G enhances the self-renewal potential of LT-HSCs. Videomicroscopy-based tracking of single LT-HSCs revealed that, once GADD45G is expressed, the development of LT-HSCs into lineage-committed progeny occurred within 36 hr and uncovered a selective lineage choice with a severe reduction in megakaryocytic-erythroid cells. Here, we report an unrecognized role of GADD45G as a central molecular linker of extrinsic cytokine differentiation and lineage choice control in hematopoiesis.

Dengue viruses in Papua New Guinea: evidence of endemicity and phylogenetic variation, including the evolution of new genetic lineages.

Science.gov (United States)

Moore, Peter R; van den Hurk, Andrew F; Mackenzie, John S; Pyke, Alyssa T

2017-12-20

Dengue is the most common cause of mosquito-borne viral disease in humans, and is endemic in more than 100 tropical and subtropical countries. Periodic outbreaks of dengue have been reported in Papua New Guinea (PNG), but there is only limited knowledge of its endemicity and disease burden. To help elucidate the status of the dengue viruses (DENVs) in PNG, we performed envelope (E) gene sequencing of DENV serotypes 1-4 (DENV 1-4) obtained from infected patients who traveled to Australia or from patients diagnosed during local DENV transmission events between 2001 and 2016. Phylogenetic analysis and comparison with globally available DENV sequences revealed new endemic PNG lineages for DENV 1-3 which have emerged within the last decade. We also identified another possible PNG lineage for DENV-4 from 2016. The DENV-1 and 3 PNG lineages were most closely related to recent lineages circulating on Pacific island nations while the DENV-2 lineage and putative DENV-4 PNG lineage were most similar to Indonesian sequences. This study has demonstrated for the first time the co-circulation of DENV 1-4 strains in PNG and provided molecular evidence of endemic DENV transmission. Our results provide an important platform for improved surveillance and monitoring of DENVs in PNG and broaden the global understanding of DENV genetic diversity.

Mechanisms of mtDNA segregation and mitochondrial signalling in cells with the pathogenic A3243G mutation

NARCIS (Netherlands)

Jahangir Tafrechi, Roshan Sakineh

2008-01-01

Using newly developed single cell A3243G mutation load assays a novel mechanism of mtDNA segregation was identified in which the multi-copy mtDNA nucleoid takes a central position. Furthermore, likely due to low level changes in gene expression, no genes or gene sets could be identified with gene

Genetic perspective of uniparental mitochondrial DNA landscape on the Punjabi population, Pakistan.

Science.gov (United States)

Bhatti, Shahzad; Abbas, Sana; Aslamkhan, Muhammad; Attimonelli, Marcella; Trinidad, Magali Segundo; Aydin, Hikmet Hakan; de Souza, Erica Martinha Silva; Gonzalez, Gerardo Rodriguez

2017-07-26

To investigate the uniparental genetic structure of the Punjabi population from mtDNA aspect and to set up an appropriate mtDNA forensic database, we studied maternally unrelated Punjabi (N = 100) subjects from two caste groups (i.e. Arain and Gujar) belonging to territory of Punjab. The complete control region was elucidated by Sanger sequencing and the subsequent 58 different haplotypes were designated into appropriate haplogroups according to the most recently updated mtDNA phylogeny. We found a homogenous dispersal of Eurasian haplogroup uniformity among the Punjab Province and exhibited a strong connotation with the European populations. Punjabi castes are primarily a composite of substantial South Asian, East Asian and West Eurasian lineages. Moreover, for the first time we have defined the newly sub-haplogroup M52b1 characterized by 16223 T, 16275 G and 16438 A in Gujar caste. The vast array of mtDNA variants displayed in this study suggested that the haplogroup composition radiates signals of extensive genetic conglomeration, population admixture and demographic expansion that was equipped with diverse origin, whereas matrilineal gene pool was phylogeographically homogenous across the Punjab. This context was further fully acquainted with the facts supported by PCA scatterplot that Punjabi population clustered with South Asian populations. Finally, the high power of discrimination (0.8819) and low random match probability (0.0085%) proposed a worthy contribution of mtDNA control region dataset as a forensic database that considered a gold standard of today to get deeper insight into the genetic ancestry of contemporary matrilineal phylogeny.

MtDNA and Y-chromosomal diversity in the Chachapoya, a population from the northeast Peruvian Andes-Amazon divide.

Science.gov (United States)

Guevara, Evelyn K; Palo, Jukka U; Guillén, Sonia; Sajantila, Antti

2016-11-01

The ancient Chachapoya were an aggregate of several ethnic groups that shared a common language, religion, and material culture. They inhabited a territory at the juncture of the Andes and the Amazon basin. Their position between those ecozones most likely influenced their genetic composition. We attempted to better understand their population history by assessing the contemporary genetic diversity in the Chachapoya and three of their immediate neighbors (Huancas, Jivaro, and Cajamarca). We inferred signatures of demographic history and genetic affinities, and contrasted the findings with data from other populations on local and continental scales. We studied mitochondrial DNA (mtDNA; hypervariable segment [HVSI and HVSII]) and Y chromosome (23 short tandem repeats (STRs)) marker data in 382 modern individuals. We used Sanger sequencing for mtDNA and a commercially available kit for Y-chromosomal STR typing. The Chachapoya had affinities with various populations of Andean and Amazonian origin. When examining the Native American component, the Chachapoya displayed high levels of genetic diversity. Together with other parameters, for example, large Tajima's D and Fu's Fs, the data indicated no drastic reduction of the population size in the past. The high level of diversity in the Chachapoya, the lack of evidence of drift in the past, and genetic affinities with a broad range of populations in the Americas reflects an intricate population history in the region. The new genetic data from the Chachapoya indeed seems to point to a genetic complexity that is not yet resolved but beginning to be elucidated. Am. J. Hum. Biol. 28:857-867, 2016. © 2016Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Allozyme and mtDNA variation of white seabream Diplodus sargus ...

African Journals Online (AJOL)

These results can be explained by the chaotic genetic patchiness hypothesis. In contrast, the mtDNA data indicated genetic homogeneity among localities showing the absence of structure in white seabream populations across the Siculo-Tunisian Strait. Historical demography of this species suggests that it has undergone ...

Land, language, and loci: mtDNA in Native Americans and the genetic history of Peru.

Science.gov (United States)

Lewis, Cecil M; Tito, Raúl Y; Lizárraga, Beatriz; Stone, Anne C

2005-07-01

Despite a long history of complex societies and despite extensive present-day linguistic and ethnic diversity, relatively few populations in Peru have been sampled for population genetic investigations. In order to address questions about the relationships between South American populations and about the extent of correlation between genetic distance, language, and geography in the region, mitochondrial DNA (mtDNA) hypervariable region I sequences and mtDNA haplogroup markers were examined in 33 individuals from the state of Ancash, Peru. These sequences were compared to those from 19 American Indian populations using diversity estimates, AMOVA tests, mismatch distributions, a multidimensional scaling plot, and regressions. The results show correlations between genetics, linguistics, and geographical affinities, with stronger correlations between genetics and language. Additionally, the results suggest a pattern of differential gene flow and drift in western vs. eastern South America, supporting previous mtDNA and Y chromosome investigations. (c) 2004 Wiley-Liss, Inc

Genetic variation among the Mapuche Indians from the Patagonian region of Argentina: mitochondrial DNA sequence variation and allele frequencies of several nuclear genes.

Science.gov (United States)

Ginther, C; Corach, D; Penacino, G A; Rey, J A; Carnese, F R; Hutz, M H; Anderson, A; Just, J; Salzano, F M; King, M C

1993-01-01

DNA samples from 60 Mapuche Indians, representing 39 maternal lineages, were genetically characterized for (1) nucleotide sequences of the mtDNA control region; (2) presence or absence of a nine base duplication in mtDNA region V; (3) HLA loci DRB1 and DQA1; (4) variation at three nuclear genes with short tandem repeats; and (5) variation at the polymorphic marker D2S44. The genetic profile of the Mapuche population was compared to other Amerinds and to worldwide populations. Two highly polymorphic portions of the mtDNA control region, comprising 650 nucleotides, were amplified by the polymerase chain reaction (PCR) and directly sequenced. The 39 maternal lineages were defined by two or three generation families identified by the Mapuches. These 39 lineages included 19 different mtDNA sequences that could be grouped into four classes. The same classes of sequences appear in other Amerinds from North, Central, and South American populations separated by thousands of miles, suggesting that the origin of the mtDNA patterns predates the migration to the Americas. The mtDNA sequence similarity between Amerind populations suggests that the migration throughout the Americas occurred rapidly relative to the mtDNA mutation rate. HLA DRB1 alleles 1602 and 1402 were frequent among the Mapuches. These alleles also occur at high frequency among other Amerinds in North and South America, but not among Spanish, Chinese or African-American populations. The high frequency of these alleles throughout the Americas, and their specificity to the Americas, supports the hypothesis that Mapuches and other Amerind groups are closely related.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary quantitative analysis of the mtDNA4977bp deletion induced by lonizing radiation in human peripheral blood u-sing real-time PCR

International Nuclear Information System (INIS)

Duan Zhikai; Liu Jiangong; Guo Wanlong; Zhang Shuxian

2011-01-01

Objective: To observe the influence of mtDNA4977bp deletion induced by different dose of γ ray in human peripheral blood in order to explore the feasibility of mtDNA4977bp deletion as biodosimeter. Methods: Human peripheral blood samples were collected from three healthy donors and irradiated by γ ray, MtDNA4977bp deletion was detected by real-time PCR. Results: It indicated that that from the range of 0 ∼ 8 Gy, the relationship between mtDNA4977bp deletion and irradiation dose represents certain curvilinear correlation (Y=1.2693+1.0660X+0.0198X 2 ). Conclusion: We find that γ ray has influence on the mtDNA4977bp deletion, so it may be an important biodosmeter in future. (authors)

The Dawn of Human Matrilineal Diversity

Science.gov (United States)

Behar, Doron M.; Villems, Richard; Soodyall, Himla; Blue-Smith, Jason; Pereira, Luisa; Metspalu, Ene; Scozzari, Rosaria; Makkan, Heeran; Tzur, Shay; Comas, David; Bertranpetit, Jaume; Quintana-Murci, Lluis; Tyler-Smith, Chris; Wells, R. Spencer; Rosset, Saharon

2008-01-01

The quest to explain demographic history during the early part of human evolution has been limited because of the scarce paleoanthropological record from the Middle Stone Age. To shed light on the structure of the mitochondrial DNA (mtDNA) phylogeny at the dawn of Homo sapiens, we constructed a matrilineal tree composed of 624 complete mtDNA genomes from sub-Saharan Hg L lineages. We paid particular attention to the Khoi and San (Khoisan) people of South Africa because they are considered to be a unique relic of hunter-gatherer lifestyle and to carry paternal and maternal lineages belonging to the deepest clades known among modern humans. Both the tree phylogeny and coalescence calculations suggest that Khoisan matrilineal ancestry diverged from the rest of the human mtDNA pool 90,000–150,000 years before present (ybp) and that at least five additional, currently extant maternal lineages existed during this period in parallel. Furthermore, we estimate that a minimum of 40 other evolutionarily successful lineages flourished in sub-Saharan Africa during the period of modern human dispersal out of Africa approximately 60,000–70,000 ybp. Only much later, at the beginning of the Late Stone Age, about 40,000 ybp, did introgression of additional lineages occur into the Khoisan mtDNA pool. This process was further accelerated during the recent Bantu expansions. Our results suggest that the early settlement of humans in Africa was already matrilineally structured and involved small, separately evolving isolated populations. PMID:18439549

Deep sequencing shows that oocytes are not prone to accumulate mtDNA heteroplasmic mutations during ovarian ageing.

Science.gov (United States)

Boucret, L; Bris, C; Seegers, V; Goudenège, D; Desquiret-Dumas, V; Domin-Bernhard, M; Ferré-L'Hotellier, V; Bouet, P E; Descamps, P; Reynier, P; Procaccio, V; May-Panloup, P

2017-10-01

Does ovarian ageing increase the number of heteroplasmic mitochondrial DNA (mtDNA) point mutations in oocytes? Our results suggest that oocytes are not subject to the accumulation of mtDNA point mutations during ovarian ageing. Ageing is associated with the alteration of mtDNA integrity in various tissues. Primary oocytes, present in the ovary since embryonic life, may accumulate mtDNA mutations during the process of ovarian ageing. This was an observational study of 53 immature oocyte-cumulus complexes retrieved from 35 women undergoing IVF at the University Hospital of Angers, France, from March 2013 to March 2014. The women were classified in two groups, one including 19 women showing signs of ovarian ageing objectified by a diminished ovarian reserve (DOR), and the other, including 16 women with a normal ovarian reserve (NOR), which served as a control group. mtDNA was extracted from isolated oocytes, and from their corresponding cumulus cells (CCs) considered as a somatic cell compartment. The average mtDNA content of each sample was assessed by using a quantitative real-time PCR technique. Deep sequencing was performed using the Ion Torrent Proton for Next-Generation Sequencing. Signal processing and base calling were done by the embedded pre-processing pipeline and the variants were analyzed using an in-house workflow. The distribution of the different variants between DOR and NOR patients, on one hand, and oocyte and CCs, on the other, was analyzed with the generalized mixed linear model to take into account the cluster of cells belonging to a given mother. There were no significant differences between the numbers of mtDNA variants between the DOR and the NOR patients, either in the oocytes (P = 0.867) or in the surrounding CCs (P = 0.154). There were also no differences in terms of variants with potential functional consequences. De-novo mtDNA variants were found in 28% of the oocytes and in 66% of the CCs with the mean number of variants being

Mutations of mtDNA polymerase-γ and hyperlactataemia in the HIV ...

African Journals Online (AJOL)

Mutations of mtDNA polymerase-γ and hyperlactataemia in the HIV-infected Zulu population of South Africa. ... D B A Ojwach, C Aldous, P Kocheleff, B Sartorius ... of their capacity to impede human mitochondrial DNA polymerase-γ (POLG), ...

mtDNA variation in caste populations of Andhra Pradesh, India.

Science.gov (United States)

Bamshad, M; Fraley, A E; Crawford, M H; Cann, R L; Busi, B R; Naidu, J M; Jorde, L B

1996-02-01

Various anthropological analyses have documented extensive regional variation among populations on the subcontinent of India using morphological, protein, blood group, and nuclear DNA polymorphisms. These patterns are the product of complex population structure (genetic drift, gene flow) and a population history noted for numerous branching events. As a result, the interpretation of relationships among caste populations of South India and between Indians and continental populations remains controversial. The Hindu caste system is a general model of genetic differentiation among endogamous populations stratified by social forces (e.g., religion and occupation). The mitochondrial DNA (mtDNA) molecule has unique properties that facilitate the exploration of population structure. We analyzed 36 Hindu men born in Andhra Pradesh who were unrelated matrilineally through at least 3 generations and who represent 4 caste populations: Brahmin (9), Yadava (10), Kapu (7), and Relli (10). Individuals from Africa (36), Asia (36), and Europe (36) were sampled for comparison. A 200-base-pair segment of hypervariable segment 2 (HVS2) of the mtDNA control region was sequenced in all individuals. In the Indian castes 25 distinct haplotypes are identified. Aside from the Cambridge reference sequence, only two haplotypes are shared between caste populations. Middle castes form a highly supported cluster in a neighbor-joining network. Mean nucleotide diversity within each caste is 0.015, 0.012, 0.011, and 0.012 for the Brahmin, Yadava, Kapu, and Relli, respectively. mtDNA variation is highly structured between castes (GST = 0.17; p caste populations of Andhra Pradesh cluster more often with Africans than with Asians or Europeans. This is suggestive of admixture with African populations.

A study of the peopling of Greenland using next generation sequencing of complete mitochondrial genomes

DEFF Research Database (Denmark)

Lopopolo, Maria; Børsting, Claus; Pereira, Vania

2016-01-01

the migration patterns in the Greenlandic population from a female inheritance demographic perspective. Methods We investigated the maternal genetic variation in the Greenlandic population by sequencing the whole mtDNA genome in 127 Greenlandic individuals using the Illumina MiSeq® platform. Results All......Objectives The Greenlandic population history is characterized by a number of migrations of people of various ethnicities. In this work, the analysis of the complete mtDNA genome aimed to contribute to the ongoing debate on the origin of current Greenlanders and, at the same time, to address...... Greenlandic individuals belonged to the Inuit mtDNA lineages A2a, A2b1, and D4b1a2a1. No European haplogroup was found. Discussion The mtDNA lineages seem to support the hypothesis that the Inuit in Greenland are descendants from the Thule migration. The results also reinforce the importance of isolation...

Yellow tails in the Red Sea: phylogeography of the Indo-Pacific goatfish Mulloidichthys flavolineatus reveals isolation in peripheral provinces and cryptic evolutionary lineages

KAUST Repository

Fernandez-Silva, Iria

2015-10-20

Aim: Broadly distributed reef fishes tend to have high gene flow mediated by a pelagic larval phase. Here, we survey a reef-associated fish distributed across half the tropical oceans, from the Red Sea to the central Pacific. Our goal is to determine whether genetic structure of the broadly distributed Yellowstripe Goatfish (Mulloidichthys flavolineatus) is defined by biogeographical barriers, or facilitated via larval dispersal. Location: Red Sea, Indian Ocean, Pacific Ocean Methods: Specimens were obtained at 19 locations from the Red Sea to Hawai\\'i. Genetic data include mtDNA cytochrome b (n = 217) and 12 microsatellite loci (n = 185). Analysis of molecular variance (AMOVA), structure, a parsimony network and coalescence analyses were used to resolve recent population history and connectivity. Results: Population structure was significant (mtDNA ϕST = 0.68, P < 0.001; microsatellite FST = 0.08, P < 0.001), but mostly driven by samples from the North-western (NW) Indian Ocean (including the Red Sea) and Hawai\\'i. There was little population structure across the Indian Ocean to the central Pacific. Hawai\\'i was distinguished as an isolated population (mtDNA ϕST = 0.03-0.08, P = n.s.; microsatellites FST = 0.05-0.10, P < 0.001). Specimens from the NW Indian Ocean clustered as a distinct phylogenetic lineage that diverged approximately 493 ka (d = 1.7%), which indicates that these fish persisted in isolation through several Pleistocene glacial cycles. Main conclusions: These data reinforce the emerging themes that: (1) phylogeographical breaks within species often coincide with biogeographical breaks based on species distributions, and (2) populations on the periphery of the range (NW Indian Ocean and Hawai\\'i) are isolated and may be evolutionary incubators producing new species. © 2015 John Wiley & Sons Ltd.

Yellow tails in the Red Sea: phylogeography of the Indo-Pacific goatfish Mulloidichthys flavolineatus reveals isolation in peripheral provinces and cryptic evolutionary lineages

KAUST Repository

Fernandez-Silva, Iria; Randall, John E.; Coleman, Richard R.; DiBattista, Joseph; Rocha, Luiz A.; Reimer, James D.; Meyer, Carl G.; Bowen, Brian W.

2015-01-01

Aim: Broadly distributed reef fishes tend to have high gene flow mediated by a pelagic larval phase. Here, we survey a reef-associated fish distributed across half the tropical oceans, from the Red Sea to the central Pacific. Our goal is to determine whether genetic structure of the broadly distributed Yellowstripe Goatfish (Mulloidichthys flavolineatus) is defined by biogeographical barriers, or facilitated via larval dispersal. Location: Red Sea, Indian Ocean, Pacific Ocean Methods: Specimens were obtained at 19 locations from the Red Sea to Hawai'i. Genetic data include mtDNA cytochrome b (n = 217) and 12 microsatellite loci (n = 185). Analysis of molecular variance (AMOVA), structure, a parsimony network and coalescence analyses were used to resolve recent population history and connectivity. Results: Population structure was significant (mtDNA ϕST = 0.68, P < 0.001; microsatellite FST = 0.08, P < 0.001), but mostly driven by samples from the North-western (NW) Indian Ocean (including the Red Sea) and Hawai'i. There was little population structure across the Indian Ocean to the central Pacific. Hawai'i was distinguished as an isolated population (mtDNA ϕST = 0.03-0.08, P = n.s.; microsatellites FST = 0.05-0.10, P < 0.001). Specimens from the NW Indian Ocean clustered as a distinct phylogenetic lineage that diverged approximately 493 ka (d = 1.7%), which indicates that these fish persisted in isolation through several Pleistocene glacial cycles. Main conclusions: These data reinforce the emerging themes that: (1) phylogeographical breaks within species often coincide with biogeographical breaks based on species distributions, and (2) populations on the periphery of the range (NW Indian Ocean and Hawai'i) are isolated and may be evolutionary incubators producing new species. © 2015 John Wiley & Sons Ltd.

Divorcing the Late Upper Palaeolithic demographic histories of mtDNA haplogroups M1 and U6 in Africa

Directory of Open Access Journals (Sweden)

Pennarun Erwan

2012-12-01

Full Text Available Abstract Background A Southwest Asian origin and dispersal to North Africa in the Early Upper Palaeolithic era has been inferred in previous studies for mtDNA haplogroups M1 and U6. Both haplogroups have been proposed to show similar geographic patterns and shared demographic histories. Results We report here 24 M1 and 33 U6 new complete mtDNA sequences that allow us to refine the existing phylogeny of these haplogroups. The resulting phylogenetic information was used to genotype a further 131 M1 and 91 U6 samples to determine the geographic spread of their sub-clades. No southwest Asian specific clades for M1 or U6 were discovered. U6 and M1 frequencies in North Africa, the Middle East and Europe do not follow similar patterns, and their sub-clade divisions do not appear to be compatible with their shared history reaching back to the Early Upper Palaeolithic. The Bayesian Skyline Plots testify to non-overlapping phases of expansion, and the haplogroups’ phylogenies suggest that there are U6 sub-clades that expanded earlier than those in M1. Some M1 and U6 sub-clades could be linked with certain events. For example, U6a1 and M1b, with their coalescent ages of ~20,000–22,000 years ago and earliest inferred expansion in northwest Africa, could coincide with the flourishing of the Iberomaurusian industry, whilst U6b and M1b1 appeared at the time of the Capsian culture. Conclusions Our high-resolution phylogenetic dissection of both haplogroups and coalescent time assessments suggest that the extant main branching pattern of both haplogroups arose and diversified in the mid-later Upper Palaeolithic, with some sub-clades concomitantly with the expansion of the Iberomaurusian industry. Carriers of these maternal lineages have been later absorbed into and diversified further during the spread of Afro-Asiatic languages in North and East Africa.

Dysphagia is prevalent in patients with CPEO and single, large-scale deletions in mtDNA

DEFF Research Database (Denmark)

Pedersen, Gitte Hedermann; Løkken, Nicoline; Dahlqvist, Julia R.

2017-01-01

Background  The aim of this study was to assess the frequency of subjective and objective dysphagia in patients with chronic progressive external ophthalmoplegia (CPEO) due to single, large-scale deletions (LSDs) of mitochondrial DNA (mtDNA). Methods  Sixteen patients with CPEO and single LSDs...... and single LSDs of mtDNA had a prolonged cold-water test, including one with a PEG-tube, who was unable to perform the test, and nine patients reported subjective swallowing problems (56.3%). All mitochondrial myopathy patients in the control group had a normal duration of the cold-water test.  Conclusions......  The study shows that dysphagia is a common problem in patients with CPEO and LSDs of mtDNA. Dysphagia seems to be progressive with age as abnormal swallowing occurred preferentially in persons ≥ 45 years. The study shows that increased awareness of this symptom should be given to address appropriate...

Genetic characterization of human T-cell lymphotropic virus type 1 in Mozambique: transcontinental lineages drive the HTLV-1 endemic.

Directory of Open Access Journals (Sweden)

Ana Carolina P Vicente

2011-04-01

Full Text Available Human T-Cell Lymphotropic Virus Type 1 (HTLV-1 is the etiological agent of adult T-cell leukemia (ATL and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. It has been estimated that 10-20 million people are infected worldwide, but no successful treatment is available. Recently, the epidemiology of this virus was addressed in blood donors from Maputo, showing rates from 0.9 to 1.2%. However, the origin and impact of HTLV endemic in this population is unknown.To assess the HTLV-1 molecular epidemiology in Mozambique and to investigate their relationship with HTLV-1 lineages circulating worldwide.Blood donors and HIV patients were screened for HTLV antibodies by using enzyme immunoassay, followed by Western Blot. PCR and sequencing of HTLV-1 LTR region were applied and genetic HTLV-1 subtypes were assigned by the neighbor-joining method. The mean genetic distance of Mozambican HTLV-1 lineages among the genetic clusters were determined. Human mitochondrial (mt DNA analysis was performed and individuals classified in mtDNA haplogroups.LTR HTLV-1 analysis demonstrated that all isolates belong to the Transcontinental subgroup of the Cosmopolitan subtype. Mozambican HTLV-1 sequences had a high inter-strain genetic distance, reflecting in three major clusters. One cluster is associated with the South Africa sequences, one is related with Middle East and India strains and the third is a specific Mozambican cluster. Interestingly, 83.3% of HIV/HTLV-1 co-infection was observed in the Mozambican cluster. The human mtDNA haplotypes revealed that all belong to the African macrohaplogroup L with frequencies representatives of the country.The Mozambican HTLV-1 genetic diversity detected in this study reveals that although the strains belong to the most prevalent and worldwide distributed Transcontinental subgroup of the Cosmopolitan subtype, there is a high HTLV diversity that could be correlated with at least 3 different HTLV-1 introductions

Thymidine Kinase 2 Deficiency-Induced mtDNA Depletion in Mouse Liver Leads to Defect beta-Oxidation

OpenAIRE

Zhou, Xiaoshan; Kannisto, Kristina; Curbo, Sophie; von Dobeln, Ulrika; Hultenby, Kjell; Isetun, Sindra; Gåfvels, Mats; Karlsson, Anna

2013-01-01

Thymidine kinase 2 (TK2) deficiency in humans causes mitochondrial DNA (mtDNA) depletion syndrome. To study the molecular mechanisms underlying the disease and search for treatment options, we previously generated and described a TK2 deficient mouse strain (TK2(-/-)) that progressively loses its mtDNA. The TK2(-/-) mouse model displays symptoms similar to humans harboring TK2 deficient infantile fatal encephalomyopathy. Here, we have studied the TK2(-/-) mouse model to clarify the pathologica...

DNA sequence evolution in fast evolving mitochondrial DNA nad1 exons in Geraniaceae and Plantaginaceae

NARCIS (Netherlands)

Bakker, F.T.; Breman, F.; Merckx, V.

2006-01-01

Previously, nucleotide substitution rates in mitochondrial DNA of Geraniaceae and Plantaginaceae have been shown to be exceptionally high compared with other angiosperm mtDNA lineages. It has also been shown that mtDNA introns were lost in Geraniaceae and Plantaginaceae. In this study we compile 127

Lineage-Restricted Mammary Stem Cells Sustain the Development, Homeostasis, and Regeneration of the Estrogen Receptor Positive Lineage.

Science.gov (United States)

Van Keymeulen, Alexandra; Fioramonti, Marco; Centonze, Alessia; Bouvencourt, Gaëlle; Achouri, Younes; Blanpain, Cédric

2017-08-15

The mammary gland (MG) is composed of different cell lineages, including the basal and the luminal cells (LCs) that are maintained by distinct stem cell (SC) populations. LCs can be subdivided into estrogen receptor (ER) + and ER - cells. LCs act as the cancer cell of origin in different types of mammary tumors. It remains unclear whether the heterogeneity found in luminal-derived mammary tumors arises from a pre-existing heterogeneity within LCs. To investigate LC heterogeneity, we used lineage tracing to assess whether the ER + lineage is maintained by multipotent SCs or by lineage-restricted SCs. To this end, we generated doxycycline-inducible ER-rtTA mice that allowed us to perform genetic lineage tracing of ER + LCs and study their fate and long-term maintenance. Our results show that ER + cells are maintained by lineage-restricted SCs that exclusively contribute to the expansion of the ER + lineage during puberty and their maintenance during adult life. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Investigational Antibody-Drug Conjugates for Treatment of B-lineage Malignancies.

Science.gov (United States)

Herrera, Alex F; Molina, Arturo

2018-05-10

Antibody-drug conjugates (ADCs) are tripartite molecules consisting of a monoclonal antibody, a covalent linker, and a cytotoxic payload. ADC development has aimed to target the specificity inherent in antigen-antibody interactions to deliver potent cytotoxins preferentially to tumor cells and maximize antitumor activity and simultaneously minimize off-target toxicity. The earliest ADCs provided disappointing results in the clinic; however, the lessons learned regarding the need for human or humanized antibodies, more stable linkers, and greater potency payloads led to improved ADCs. Three ADCs, gemtuzumab ozogamicin, brentuximab vedotin (BV), and inotuzumab ozogamicin, have been approved for hematologic malignancies. Site-specific conjugation methods have now resulted in a new generation of more uniform, molecularly defined ADCs. These are expected to display improved in vivo properties and have recently entered the clinic. We reviewed investigational ADCs currently in clinical testing for the treatment of B-cell lineage malignancies, including leukemias, lymphomas, and multiple myeloma. The rationales for antigen targeting, data reported to date, current trial status, and preclinical results for several newer ADCs expected to enter first-in-human studies are presented. Owing to the large number of ongoing and reported BV clinical studies, only the studies of BV for diffuse large B-cell lymphoma and those combining BV with checkpoint inhibitors in B-lineage malignancies have been reviewed. With > 40 ongoing clinical trials and 7 investigational ADCs already having advanced to phase II studies, the role of ADCs in the armamentarium for the treatment of B-lineage malignancies continues to be elucidated. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Human settlement history between Sunda and Sahul: a focus on East Timor (Timor-Leste) and the Pleistocenic mtDNA diversity.

Science.gov (United States)

Gomes, Sibylle M; Bodner, Martin; Souto, Luis; Zimmermann, Bettina; Huber, Gabriela; Strobl, Christina; Röck, Alexander W; Achilli, Alessandro; Olivieri, Anna; Torroni, Antonio; Côrte-Real, Francisco; Parson, Walther

2015-02-14

Distinct, partly competing, "waves" have been proposed to explain human migration in(to) today's Island Southeast Asia and Australia based on genetic (and other) evidence. The paucity of high quality and high resolution data has impeded insights so far. In this study, one of the first in a forensic environment, we used the Ion Torrent Personal Genome Machine (PGM) for generating complete mitogenome sequences via stand-alone massively parallel sequencing and describe a standard data validation practice. In this first representative investigation on the mitochondrial DNA (mtDNA) variation of East Timor (Timor-Leste) population including >300 individuals, we put special emphasis on the reconstruction of the initial settlement, in particular on the previously poorly resolved haplogroup P1, an indigenous lineage of the Southwest Pacific region. Our results suggest a colonization of southern Sahul (Australia) >37 kya, limited subsequent exchange, and a parallel incubation of initial settlers in northern Sahul (New Guinea) followed by westward migrations <28 kya. The temporal proximity and possible coincidence of these latter dispersals, which encompassed autochthonous haplogroups, with the postulated "later" events of (South) East Asian origin pinpoints a highly dynamic migratory phase.

Y-chromosome and mtDNA genetics reveal significant contrasts in affinities of modern Middle Eastern populations with European and African populations.

Science.gov (United States)

Badro, Danielle A; Douaihy, Bouchra; Haber, Marc; Youhanna, Sonia C; Salloum, Angélique; Ghassibe-Sabbagh, Michella; Johnsrud, Brian; Khazen, Georges; Matisoo-Smith, Elizabeth; Soria-Hernanz, David F; Wells, R Spencer; Tyler-Smith, Chris; Platt, Daniel E; Zalloua, Pierre A

2013-01-01

The Middle East was a funnel of human expansion out of Africa, a staging area for the Neolithic Agricultural Revolution, and the home to some of the earliest world empires. Post LGM expansions into the region and subsequent population movements created a striking genetic mosaic with distinct sex-based genetic differentiation. While prior studies have examined the mtDNA and Y-chromosome contrast in focal populations in the Middle East, none have undertaken a broad-spectrum survey including North and sub-Saharan Africa, Europe, and Middle Eastern populations. In this study 5,174 mtDNA and 4,658 Y-chromosome samples were investigated using PCA, MDS, mean-linkage clustering, AMOVA, and Fisher exact tests of F(ST)'s, R(ST)'s, and haplogroup frequencies. Geographic differentiation in affinities of Middle Eastern populations with Africa and Europe showed distinct contrasts between mtDNA and Y-chromosome data. Specifically, Lebanon's mtDNA shows a very strong association to Europe, while Yemen shows very strong affinity with Egypt and North and East Africa. Previous Y-chromosome results showed a Levantine coastal-inland contrast marked by J1 and J2, and a very strong North African component was evident throughout the Middle East. Neither of these patterns were observed in the mtDNA. While J2 has penetrated into Europe, the pattern of Y-chromosome diversity in Lebanon does not show the widespread affinities with Europe indicated by the mtDNA data. Lastly, while each population shows evidence of connections with expansions that now define the Middle East, Africa, and Europe, many of the populations in the Middle East show distinctive mtDNA and Y-haplogroup characteristics that indicate long standing settlement with relatively little impact from and movement into other populations.

An economical mtDNA SNP assay detecting different mitochondrial haplogroups in identical HVR 1 samples of Caucasian ancestry.

Science.gov (United States)

Köhnemann, Stephan; Hohoff, Carsten; Pfeiffer, Heidi

2009-09-01

We had sequenced 329 Caucasian samples in Hypervariable Region 1 (HVR 1) and found that they belong to eleven different mitochondrial DNA (mtDNA) haplotypes. The sample set was further analysed by an mtDNA assay examining 32 single nucleotide polymorphisms (SNPs) for haplogroup discrimination. In a validation study on 160 samples of different origin it was shown that these SNPs were able to discriminate between the evolved superhaplogroups worldwide (L, M and N) and between the nine most common Caucasian haplogroups (H, I, J, K, T, U, V, W and X). The 32 mtDNA SNPs comprised 42 different SNP haplotypes instead of only eleven haplotypes after HVR 1 sequencing. The assay provided stable results in a range of 5ng genomic DNA down to virtually no genomic DNA per reaction. It was possible to detect samples of African, Asian and Eurasian ancestry, respectively. The 32 mtDNA SNP assay is a helpful adjunct to further distinguish between identical HVR 1 sequences of Caucasian origin. Our results suggest that haplogroup prediction using HVR 1 sequencing provides instable results. The use of coding region SNPs for haplogroup assignment is more suited than using HVR 1 haplotypes.

The mtDNA haplogroup P of modern Asian cattle: A genetic legacy of Asian aurochs?

Science.gov (United States)

Noda, Aoi; Yonesaka, Riku; Sasazaki, Shinji

2018-01-01

Background Aurochs (Bos primigenius) were distributed throughout large parts of Eurasia and Northern Africa during the late Pleistocene and the early Holocene, and all modern cattle are derived from the aurochs. Although the mtDNA haplogroups of most modern cattle belong to haplogroups T and I, several additional haplogroups (P, Q, R, C and E) have been identified in modern cattle and aurochs. Haplogroup P was the most common haplogroup in European aurochs, but so far, it has been identified in only three of >3,000 submitted haplotypes of modern Asian cattle. Methodology We sequenced the complete mtDNA D-loop region of 181 Japanese Shorthorn cattle and analyzed these together with representative bovine mtDNA sequences. The haplotype P of Japanese Shorthorn cattle was analyzed along with that of 36 previously published European aurochs and three modern Asian cattle sequences using the hypervariable 410 bp of the D-loop region. Conclusions We detected the mtDNA haplogroup P in Japanese Shorthorn cattle with an extremely high frequency (83/181). Phylogenetic networks revealed two main clusters, designated as Pa for haplogroup P in European aurochs and Pc in modern Asian cattle. We also report the genetic diversity of haplogroup P compared with the sequences of extinct aurochs. No shared haplotypes are observed between the European aurochs and the modern Asian cattle. This finding suggests the possibility of local and secondary introgression events of haplogroup P in northeast Asian cattle, and will contribute to a better understanding of its origin and genetic diversity. PMID:29304129

The mtDNA haplogroup P of modern Asian cattle: A genetic legacy of Asian aurochs?

Science.gov (United States)

Noda, Aoi; Yonesaka, Riku; Sasazaki, Shinji; Mannen, Hideyuki

2018-01-01

Aurochs (Bos primigenius) were distributed throughout large parts of Eurasia and Northern Africa during the late Pleistocene and the early Holocene, and all modern cattle are derived from the aurochs. Although the mtDNA haplogroups of most modern cattle belong to haplogroups T and I, several additional haplogroups (P, Q, R, C and E) have been identified in modern cattle and aurochs. Haplogroup P was the most common haplogroup in European aurochs, but so far, it has been identified in only three of >3,000 submitted haplotypes of modern Asian cattle. We sequenced the complete mtDNA D-loop region of 181 Japanese Shorthorn cattle and analyzed these together with representative bovine mtDNA sequences. The haplotype P of Japanese Shorthorn cattle was analyzed along with that of 36 previously published European aurochs and three modern Asian cattle sequences using the hypervariable 410 bp of the D-loop region. We detected the mtDNA haplogroup P in Japanese Shorthorn cattle with an extremely high frequency (83/181). Phylogenetic networks revealed two main clusters, designated as Pa for haplogroup P in European aurochs and Pc in modern Asian cattle. We also report the genetic diversity of haplogroup P compared with the sequences of extinct aurochs. No shared haplotypes are observed between the European aurochs and the modern Asian cattle. This finding suggests the possibility of local and secondary introgression events of haplogroup P in northeast Asian cattle, and will contribute to a better understanding of its origin and genetic diversity.

Identification of two invasive Cacopsylla chinensis (Hemiptera: Psyllidae) lineages based on two mitochondrial sequences and restriction fragment length polymorphism of cytochrome oxidase I amplicon.

Science.gov (United States)

Lee, Hsien-Chung; Yang, Man-Miao; Yeh, Wen-Bin

2008-08-01

The occurrence of pear decline, a disease found in some pear (Pyrus spp.) orchards of Taiwan in recent years, is accompanied by an outbreak of Cacopsylla chinensis (Yang & Li). Two major morphological forms (summer and winter forms) with a variety of intermediate body color and two phylogenetic lineages of this psyllid have been described. The work herein used sequences of mitochondrial cytochrome oxidase I (COI) and 16S rDNA regions to delineate the genetic differentiation of this color-variable insect and to elucidate their relationship. Sequence divergence and phylogenetic analysis have shown that C. chinensis individuals could be divided into two lineages with 3.3 and 2.3% divergence of COI and 16S rDNA, respectively. All specimens from China were found to belong to lineage I. Restriction fragment length polymorphism analysis of COI with restriction enzymes AcuI, AseI, BccI, and FokI on 263 specimens of six populations from Taiwan produced two digestion patterns, which are in agreement with the two lineages described above. Both patterns could be found in each population, with most individuals belonging to lineage I and 5-21% of the individuals belonging to lineage II. Because these two lineages included summer as well as winter morphological forms, the lineage differentiation is apparently not related to morphological characters of this psyllid. Because the invasive records are not in favor of a sympatric differentiation, this psyllid is more likely introduced as different populations from countries in temperate regions.

eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies

Directory of Open Access Journals (Sweden)

Specht Günther

2010-03-01

Full Text Available Abstract Background Mitochondrial DNA (mtDNA is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. Description eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle, security aspects (by using database technology and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs. It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. Conclusions The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

eCOMPAGT integrates mtDNA: import, validation and export of mitochondrial DNA profiles for population genetics, tumour dynamics and genotype-phenotype association studies.

Science.gov (United States)

Weissensteiner, Hansi; Schönherr, Sebastian; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

2010-03-09

Mitochondrial DNA (mtDNA) is widely being used for population genetics, forensic DNA fingerprinting and clinical disease association studies. The recent past has uncovered severe problems with mtDNA genotyping, not only due to the genotyping method itself, but mainly to the post-lab transcription, storage and report of mtDNA genotypes. eCOMPAGT, a system to store, administer and connect phenotype data to all kinds of genotype data is now enhanced by the possibility of storing mtDNA profiles and allowing their validation, linking to phenotypes and export as numerous formats. mtDNA profiles can be imported from different sequence evaluation programs, compared between evaluations and their haplogroup affiliations stored. Furthermore, eCOMPAGT has been improved in its sophisticated transparency (support of MySQL and Oracle), security aspects (by using database technology) and the option to import, manage and store genotypes derived from various genotyping methods (SNPlex, TaqMan, and STRs). It is a software solution designed for project management, laboratory work and the evaluation process all-in-one. The extended mtDNA version of eCOMPAGT was designed to enable error-free post-laboratory data handling of human mtDNA profiles. This software is suited for small to medium-sized human genetic, forensic and clinical genetic laboratories. The direct support of MySQL and the improved database security options render eCOMPAGT a powerful tool to build an automated workflow architecture for several genotyping methods. eCOMPAGT is freely available at http://dbis-informatik.uibk.ac.at/ecompagt.

Uncovering the mutation-fixation correlation in short lineages

Directory of Open Access Journals (Sweden)

Vallender Eric J

2007-09-01

Full Text Available Abstract Background We recently reported a highly unexpected positive correlation between the fixation probability of nonsynonymous mutations (estimated by ω and neutral mutation rate (estimated by Ks in mammalian lineages. However, this positive correlation was observed for lineages with relatively long divergence time such as the human-mouse lineage, and was not found for very short lineages such as the human-chimpanzee lineage. It was previously unclear how to interpret this discrepancy. It may indicate that the positive correlation between ω and Ks in long lineages is a false finding. Alternatively, it may reflect a biologically meaningful difference between various lineages. Finally, the lack of positive correlation in short lineages may be the result of methodological artifacts. Results Here we show that a strong positive correlation can indeed be seen in short lineages when a method was introduced to correct for the inherently high levels of stochastic noise in the use of Ks as an estimator of neutral mutation rate. Thus, the previously noted lack of positive correlation between ω and Ks in short lineages is due to stochastic noise in Ks that makes it a far less reliable estimator of neutral mutation rate in short lineages as compared to long lineages. Conclusion A positive correlation between ω and Ks can be observed in all mammalian lineages for which large amounts of sequence data are available, including very short lineages. It confirms the authenticity of this highly unexpected correlation, and argues that the correction likely applies broadly across all mammals and perhaps even non-mammalian species.

Cytoplasmic transfer of heritable elements other than mtDNA from SAMP1 mice into mouse tumor cells suppresses their ability to form tumors in C57BL6 mice.

Science.gov (United States)

Shimizu, Akinori; Tani, Haruna; Takibuchi, Gaku; Ishikawa, Kaori; Sakurazawa, Ryota; Inoue, Takafumi; Hashimoto, Tetsuo; Nakada, Kazuto; Takenaga, Keizo; Hayashi, Jun-Ichi

2017-11-04

In a previous study, we generated transmitochondrial P29mtSAMP1 cybrids, which had nuclear DNA from the C57BL6 (referred to as B6) mouse strain-derived P29 tumor cells and mitochondrial DNA (mtDNA) exogenously-transferred from the allogeneic strain SAMP1. Because P29mtSAMP1 cybrids did not form tumors in syngeneic B6 mice, we proposed that allogeneic SAMP1 mtDNA suppressed tumor formation of P29mtSAMP1 cybrids. To test this hypothesis, current study generated P29mt(sp)B6 cybrids carrying all genomes (nuclear DNA and mtDNA) from syngeneic B6 mice by eliminating SAMP1 mtDNA from P29mtSAMP1 cybrids and reintroducing B6 mtDNA. However, the P29mt(sp)B6 cybrids did not form tumors in B6 mice, even though they had no SAMP1 mtDNA, suggesting that SAMP1 mtDNA is not involved in tumor suppression. Then, we examined another possibility of whether SAMP1 mtDNA fragments potentially integrated into the nuclear DNA of P29mtSAMP1 cybrids are responsible for tumor suppression. We generated P29 H (sp)B6 cybrids by eliminating nuclear DNA from P29mt(sp)B6 cybrids and reintroducing nuclear DNA with no integrated SAMP1 mtDNA fragment from mtDNA-less P29 cells resistant to hygromycin in selection medium containing hygromycin. However, the P29 H (sp)B6 cybrids did not form tumors in B6 mice, even though they carried neither SAMP1 mtDNA nor nuclear DNA with integrated SAMP1 mtDNA fragments. Moreover, overproduction of reactive oxygen species (ROS) and bacterial infection were not involved in tumor suppression. These observations suggest that tumor suppression was caused not by mtDNA with polymorphic mutations or infection of cytozoic bacteria but by hypothetical heritable cytoplasmic elements other than mtDNA from SAMP1 mice. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Quantification of crypt and stem cell evolution in the normal and neoplastic human colon

NARCIS (Netherlands)

Baker, Ann-Marie; Cereser, Biancastella; Melton, Samuel; Fletcher, Alexander G.; Rodriguez-Justo, Manuel; Tadrous, Paul J.; Humphries, Adam; Elia, George; McDonald, Stuart A. C.; Wright, Nicholas A.; Simons, Benjamin D.; Jansen, Marnix; Graham, Trevor A.

2014-01-01

Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls

Does aerobic exercises induce mtDNA mutation in human blood ...

African Journals Online (AJOL)

The aim of this study was to determine the effect of eight weeks aerobic training on mitochondrial DNA (mtDNA) mutation in human blood leucocytes. Twenty untrained healthy students (training group: n =10, age = 20.7±1.5 yrs, weight = 67.7±10 kg, BF% = 17.5±7.35 & control group: n =10, age = 21±1.3 yrs, weight ...

The Mitochondrial DNA (mtDNA)-Associated Protein SWIB5 Influences mtDNA Architecture and Homologous Recombination

KAUST Repository

Blomme, Jonas

2017-04-19

In addition to the nucleus, mitochondria and chloroplasts in plant cells also contain genomes. Efficient DNA repair pathways are crucial in these organelles to fix damage resulting from endogenous and exogenous factors. Plant organellar genomes are complex compared with their animal counterparts, and although several plant-specific mediators of organelle DNA repair have been reported, many regulators remain to be identified. Here, we show that a mitochondrial SWI/SNF (nucleosome remodeling) complex B protein, SWIB5, is capable of associating with mitochondrial DNA (mtDNA) in Arabidopsis thaliana. Gainand loss-of-function mutants provided evidence for a role of SWIB5 in influencing mtDNA architecture and homologous recombination at specific intermediate-sized repeats both under normal and genotoxic conditions. SWIB5 interacts with other mitochondrial SWIB proteins. Gene expression and mutant phenotypic analysis of SWIB5 and SWIB family members suggests a link between organellar genome maintenance and cell proliferation. Taken together, our work presents a protein family that influences mtDNA architecture and homologous recombination in plants and suggests a link between organelle functioning and plant development.

Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia.

Science.gov (United States)

Torrell, Helena; Salas, Antonio; Abasolo, Nerea; Morén, Constanza; Garrabou, Glòria; Valero, Joaquín; Alonso, Yolanda; Vilella, Elisabet; Costas, Javier; Martorell, Lourdes

2014-10-01

It has been reported that certain genetic factors involved in schizophrenia could be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that mtDNA mutations and/or variants would be present in schizophrenia patients and may be related to schizophrenia characteristics and mitochondrial function. This study was performed in three steps: (1) identification of pathogenic mutations and variants in 14 schizophrenia patients with an apparent maternal inheritance of the disease by sequencing the entire mtDNA; (2) case-control association study of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in 495 patients and 615 controls, and (3) analyses of the associated variants according to the clinical, psychopathological, and neuropsychological characteristics and according to the oxidative and enzymatic activities of the mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations in the 14 sequenced patients. Two known variants were nominally associated with schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does not play a major role in schizophrenia, as it was not associated with clinical, psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C p.Ile195Thr variant did not result in differences in the oxidative and enzymatic functions of the mitochondrial respiratory chain. The patients with apparent maternal inheritance of schizophrenia did not exhibit any mutations in their mtDNA. The variants nominally associated with schizophrenia in the present study were not related either to phenotypic characteristics or to mitochondrial function. We did not find evidence pointing to a role for mtDNA sequence variation in schizophrenia. © 2014 Wiley Periodicals, Inc.

Rapid radiations of both kiwifruit hybrid lineages and their parents shed light on a two-layer mode of species diversification.

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Liu, Yifei; Li, Dawei; Zhang, Qiong; Song, Chi; Zhong, Caihong; Zhang, Xudong; Wang, Ying; Yao, Xiaohong; Wang, Zupeng; Zeng, Shaohua; Wang, Ying; Guo, Yangtao; Wang, Shuaibin; Li, Xinwei; Li, Li; Liu, Chunyan; McCann, Honour C; He, Weiming; Niu, Yan; Chen, Min; Du, Liuwen; Gong, Junjie; Datson, Paul M; Hilario, Elena; Huang, Hongwen

2017-07-01

Reticulate speciation caused by interspecific hybridization is now recognized as an important mechanism in the creation of biological diversity. However, depicting the patterns of phylogenetic networks for lineages that have undergone interspecific gene flow is challenging. Here we sequenced 25 taxa representing natural diversity in the genus Actinidia with an average mapping depth of 26× on the reference genome to reconstruct their reticulate history. We found evidence, including significant gene tree discordance, cytonuclear conflicts, and changes in genome-wide heterozygosity across taxa, collectively supporting extensive reticulation in the genus. Furthermore, at least two separate parental species pairs were involved in the repeated origin of the hybrid lineages, in some of which a further phase of syngameon was triggered. On the basis of the elucidated hybridization relationships, we obtained a highly resolved backbone phylogeny consisting of taxa exhibiting no evidence of hybrid origin. The backbone taxa have distinct demographic histories and are the product of recent rounds of rapid radiations via sorting of ancestral variation under variable climatic and ecological conditions. Our results suggest a mode for consecutive plant diversification through two layers of radiations, consisting of the rapid evolution of backbone lineages and the formation of hybrid swarms derived from these lineages. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Anti-replicative recombinant 5S rRNA molecules can modulate the mtDNA heteroplasmy in a glucose-dependent manner.

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Loutre, Romuald; Heckel, Anne-Marie; Jeandard, Damien; Tarassov, Ivan; Entelis, Nina

2018-01-01

Mutations in mitochondrial DNA are an important source of severe and incurable human diseases. The vast majority of these mutations are heteroplasmic, meaning that mutant and wild-type genomes are present simultaneously in the same cell. Only a very high proportion of mutant mitochondrial DNA (heteroplasmy level) leads to pathological consequences. We previously demonstrated that mitochondrial targeting of small RNAs designed to anneal with mutant mtDNA can decrease the heteroplasmy level by specific inhibition of mutant mtDNA replication, thus representing a potential therapy. We have also shown that 5S ribosomal RNA, partially imported into human mitochondria, can be used as a vector to deliver anti-replicative oligoribonucleotides into human mitochondria. So far, the efficiency of cellular expression of recombinant 5S rRNA molecules bearing therapeutic insertions remained very low. In the present study, we designed new versions of anti-replicative recombinant 5S rRNA targeting a large deletion in mitochondrial DNA which causes the KSS syndrome, analyzed their specific annealing to KSS mitochondrial DNA and demonstrated their import into mitochondria of cultured human cells. To obtain an increased level of the recombinant 5S rRNA stable expression, we created transmitochondrial cybrid cell line bearing a site for Flp-recombinase and used this system for the recombinase-mediated integration of genes coding for the anti-replicative recombinant 5S rRNAs into nuclear genome. We demonstrated that stable expression of anti-replicative 5S rRNA versions in human transmitochondrial cybrid cells can induce a shift in heteroplasmy level of KSS mutation in mtDNA. This shift was directly dependent on the level of the recombinant 5S rRNA expression and the sequence of the anti-replicative insertion. Quantification of mtDNA copy number in transfected cells revealed the absence of a non-specific effect on wild type mtDNA replication, indicating that the decreased proportion

Phylogeography of the arid-adapted Malagasy bullfrog, Laliostoma labrosum, influenced by past connectivity and habitat stability.

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Pabijan, Maciej; Brown, Jason L; Chan, Lauren M; Rakotondravony, Hery A; Raselimanana, Achille P; Yoder, Anne D; Glaw, Frank; Vences, Miguel

2015-11-01

The rainforest biome of eastern Madagascar is renowned for its extraordinary biodiversity and restricted distribution ranges of many species, whereas the arid western region of the island is relatively species poor. We provide insight into the biogeography of western Madagascar by analyzing a multilocus phylogeographic dataset assembled for an amphibian, the widespread Malagasy bullfrog, Laliostoma labrosum. We find no cryptic species in L. labrosum (maximum 1.1% pairwise genetic distance between individuals in the 16S rRNA gene) attributable to considerable gene flow at the regional level as shown by genetic admixture in both mtDNA and three nuclear loci, especially in central Madagascar. Low breeding site fidelity, viewed as an adaptation to the unreliability of standing pools of freshwater in dry and seasonal environments, and a ubiquitous distribution within its range may underlie overall low genetic differentiation. Moreover, reductions in population size associated with periods of high aridity in western Madagascar may have purged DNA variation in this species. The mtDNA gene tree revealed seven major phylogroups within this species, five of which show mostly non-overlapping distributions. The nested positions of the northern and central mtDNA phylogroups imply a southwestern origin for all extant mtDNA lineages in L. labrosum. The current phylogeography of this species and paleo-distributions of major mtDNA lineages suggest five potential refugia in northern, western and southwestern Madagascar, likely the result of Pleistocene range fragmentation during drier and cooler climates. Lineage sorting in mtDNA and nuclear loci highlighted a main phylogeographic break between populations north and south of the Sambirano region, suggesting a role of the coastal Sambirano rainforest as a barrier to gene flow. Paleo-species distribution models and dispersal networks suggest that the persistence of some refugial populations was mainly determined by high population

Somatic point mutations in mtDNA control region are influenced by genetic background and associated with healthy aging: a GEHA study

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Rose, Giuseppina; Romeo, Giuseppe; Dato, Serena

2010-01-01

and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions....

Genetic diversity of mtDNA D-loop sequences in four native Chinese chicken breeds.

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Guo, H W; Li, C; Wang, X N; Li, Z J; Sun, G R; Li, G X; Liu, X J; Kang, X T; Han, R L

2017-10-01

1. To explore the genetic diversity of Chinese indigenous chicken breeds, a 585 bp fragment of the mitochondrial DNA (mtDNA) region was sequenced in 102 birds from the Xichuan black-bone chicken, Yunyang black-bone chicken and Lushi chicken. In addition, 30 mtDNA D-loop sequences of Silkie fowls were downloaded from NCBI. The mtDNA D-loop sequence polymorphism and maternal origin of 4 chicken breeds were analysed in this study. 2. The results showed that a total of 33 mutation sites and 28 haplotypes were detected in the 4 chicken breeds. The haplotype diversity and nucleotide diversity of these 4 native breeds were 0.916 ± 0.014 and 0.012 ± 0.002, respectively. Three clusters were formed in 4 Chinese native chickens and 12 reference breeds. Both the Xichuan black-bone chicken and Yunyang black-bone chicken were grouped into one cluster. Four haplogroups (A, B, C and E) emerged in the median-joining network in these breeds. 3. It was concluded that these 4 Chinese chicken breeds had high genetic diversity. The phylogenetic tree and median network profiles showed that Chinese native chickens and its neighbouring countries had at least two maternal origins, one from Yunnan, China and another from Southeast Asia or its surrounding area.

Human aging and somatic point mutations in mtDNA: a comparative study of generational differences (grandparents and grandchildren

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Anderson Nonato do Rosário Marinho

2011-01-01

Full Text Available The accumulation of somatic mutations in mtDNA is correlated with aging. In this work, we sought to identify somatic mutations in the HVS-1 region (D-loop of mtDNA that might be associated with aging. For this, we compared 31 grandmothers (mean age: 63 ± 2.3 years and their 62 grandchildren (mean age: 15 ± 4.1 years, the offspring of their daughters. Direct DNA sequencing showed that mutations absent in the grandchildren were detected in a presumably homoplasmic state in three grandmothers and in a heteroplasmic state in an additional 13 grandmothers; no mutations were detected in the remaining 15 grandmothers. However, cloning followed by DNA sequencing in 12 grandmothers confirmed homoplasia in only one of the three mutations previously considered to be homoplasmic and did not confirm heteroplasmy in three out of nine grandmothers found to be heteroplasmic by direct sequencing. Thus, of 12 grandmothers in whom mtDNA was analyzed by cloning, eight were heteroplasmic for mutations not detected in their grandchildren. In this study, the use of genetically related subjects allowed us to demonstrate the occurrence of age-related (> 60 years old mutations (homoplasia and heteroplasmy. It is possible that both of these situations (homoplasia and heteroplasmy were a long-term consequence of mitochondrial oxidative phosphorylation that can lead to the accumulation of mtDNA mutations throughout life.

Linking Compositional and Functional Predictions to Decipher the Biogeochemical Significance in DFAA Turnover of Abundant Bacterioplankton Lineages in the North Sea

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Bernd Wemheuer

2017-11-01

Full Text Available Deciphering the ecological traits of abundant marine bacteria is a major challenge in marine microbial ecology. In the current study, we linked compositional and functional predictions to elucidate such traits for abundant bacterioplankton lineages in the North Sea. For this purpose, we investigated entire and active bacterioplankton composition along a transect ranging from the German Bight to the northern North Sea by pyrotag sequencing of bacterial 16S rRNA genes and transcripts. Functional profiles were inferred from 16S rRNA data using Tax4Fun. Bacterioplankton communities were dominated by well-known marine lineages including clusters/genera that are affiliated with the Roseobacter group and the Flavobacteria. Variations in community composition and function were significantly explained by measured environmental and microbial properties. Turnover of dissolved free amino acids (DFAA showed the strongest correlation to community composition and function. We applied multinomial models, which enabled us to identify bacterial lineages involved in DFAA turnover. For instance, the genus Planktomarina was more abundant at higher DFAA turnover rates, suggesting its vital role in amino acid degradation. Functional predictions further indicated that Planktomarina is involved in leucine and isoleucine degradation. Overall, our results provide novel insights into the biogeochemical significance of abundant bacterioplankton lineages in the North Sea.

Linking Compositional and Functional Predictions to Decipher the Biogeochemical Significance in DFAA Turnover of Abundant Bacterioplankton Lineages in the North Sea.

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Wemheuer, Bernd; Wemheuer, Franziska; Meier, Dimitri; Billerbeck, Sara; Giebel, Helge-Ansgar; Simon, Meinhard; Scherber, Christoph; Daniel, Rolf

2017-11-05

Deciphering the ecological traits of abundant marine bacteria is a major challenge in marine microbial ecology. In the current study, we linked compositional and functional predictions to elucidate such traits for abundant bacterioplankton lineages in the North Sea. For this purpose, we investigated entire and active bacterioplankton composition along a transect ranging from the German Bight to the northern North Sea by pyrotag sequencing of bacterial 16S rRNA genes and transcripts. Functional profiles were inferred from 16S rRNA data using Tax4Fun. Bacterioplankton communities were dominated by well-known marine lineages including clusters/genera that are affiliated with the Roseobacter group and the Flavobacteria . Variations in community composition and function were significantly explained by measured environmental and microbial properties. Turnover of dissolved free amino acids (DFAA) showed the strongest correlation to community composition and function. We applied multinomial models, which enabled us to identify bacterial lineages involved in DFAA turnover. For instance, the genus Planktomarina was more abundant at higher DFAA turnover rates, suggesting its vital role in amino acid degradation. Functional predictions further indicated that Planktomarina is involved in leucine and isoleucine degradation. Overall, our results provide novel insights into the biogeochemical significance of abundant bacterioplankton lineages in the North Sea.

Quantitation of heteroplasmy of mtDNA sequence variants identified in a population of AD patients and controls by array-based resequencing.

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Coon, Keith D; Valla, Jon; Szelinger, Szabolics; Schneider, Lonnie E; Niedzielko, Tracy L; Brown, Kevin M; Pearson, John V; Halperin, Rebecca; Dunckley, Travis; Papassotiropoulos, Andreas; Caselli, Richard J; Reiman, Eric M; Stephan, Dietrich A

2006-08-01

The role of mitochondrial dysfunction in the pathogenesis of Alzheimer's disease (AD) has been well documented. Though evidence for the role of mitochondria in AD seems incontrovertible, the impact of mitochondrial DNA (mtDNA) mutations in AD etiology remains controversial. Though mutations in mitochondrially encoded genes have repeatedly been implicated in the pathogenesis of AD, many of these studies have been plagued by lack of replication as well as potential contamination of nuclear-encoded mitochondrial pseudogenes. To assess the role of mtDNA mutations in the pathogenesis of AD, while avoiding the pitfalls of nuclear-encoded mitochondrial pseudogenes encountered in previous investigations and showcasing the benefits of a novel resequencing technology, we sequenced the entire coding region (15,452 bp) of mtDNA from 19 extremely well-characterized AD patients and 18 age-matched, unaffected controls utilizing a new, reliable, high-throughput array-based resequencing technique, the Human MitoChip. High-throughput, array-based DNA resequencing of the entire mtDNA coding region from platelets of 37 subjects revealed the presence of 208 loci displaying a total of 917 sequence variants. There were no statistically significant differences in overall mutational burden between cases and controls, however, 265 independent sites of statistically significant change between cases and controls were identified. Changed sites were found in genes associated with complexes I (30.2%), III (3.0%), IV (33.2%), and V (9.1%) as well as tRNA (10.6%) and rRNA (14.0%). Despite their statistical significance, the subtle nature of the observed changes makes it difficult to determine whether they represent true functional variants involved in AD etiology or merely naturally occurring dissimilarity. Regardless, this study demonstrates the tremendous value of this novel mtDNA resequencing platform, which avoids the pitfalls of erroneously amplifying nuclear-encoded mtDNA pseudogenes, and

Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa.

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Bertola, Laura D; Tensen, Laura; van Hooft, Pim; White, Paula A; Driscoll, Carlos A; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A; Tumenta, Pricelia N; Jirmo, Tuqa H; de Snoo, Geert R; de Iongh, Hans H; Vrieling, Klaas

2015-01-01

The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.

Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa.

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Laura D Bertola

Full Text Available The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1 West/Central Africa, 2 East Africa, 3 Southern Africa and 4 India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.

Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa

Science.gov (United States)

Bertola, Laura D.; Tensen, Laura; van Hooft, Pim; White, Paula A.; Driscoll, Carlos A.; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A.; Tumenta, Pricelia N.; Jirmo, Tuqa H.; de Snoo, Geert R.

2015-01-01

The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted. PMID:26466139

Lineage specific recombination rates and microevolution in Listeria monocytogenes

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Nightingale Kendra K

2008-10-01

Full Text Available Abstract Background The bacterium Listeria monocytogenes is a saprotroph as well as an opportunistic human foodborne pathogen, which has previously been shown to consist of at least two widespread lineages (termed lineages I and II and an uncommon lineage (lineage III. While some L. monocytogenes strains show evidence for considerable diversification by homologous recombination, our understanding of the contribution of recombination to L. monocytogenes evolution is still limited. We therefore used STRUCTURE and ClonalFrame, two programs that model the effect of recombination, to make inferences about the population structure and different aspects of the recombination process in L. monocytogenes. Analyses were performed using sequences for seven loci (including the house-keeping genes gap, prs, purM and ribC, the stress response gene sigB, and the virulence genes actA and inlA for 195 L. monocytogenes isolates. Results Sequence analyses with ClonalFrame and the Sawyer's test showed that recombination is more prevalent in lineage II than lineage I and is most frequent in two house-keeping genes (ribC and purM and the two virulence genes (actA and inlA. The relative occurrence of recombination versus point mutation is about six times higher in lineage II than in lineage I, which causes a higher genetic variability in lineage II. Unlike lineage I, lineage II represents a genetically heterogeneous population with a relatively high proportion (30% average of genetic material imported from external sources. Phylograms, constructed with correcting for recombination, as well as Tajima's D data suggest that both lineages I and II have suffered a population bottleneck. Conclusion Our study shows that evolutionary lineages within a single bacterial species can differ considerably in the relative contributions of recombination to genetic diversification. Accounting for recombination in phylogenetic studies is critical, and new evolutionary models that

Do holocentric chromosomes represent an evolutionary advantage? A study of paired analyses of diversification rates of lineages with holocentric chromosomes and their monocentric closest relatives.

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Márquez-Corro, José Ignacio; Escudero, Marcial; Luceño, Modesto

2017-10-17

Despite most of the cytogenetic research is focused on monocentric chromosomes, chromosomes with kinetochoric activity localized in a single centromere, several studies have been centered on holocentric chromosomes which have diffuse kinetochoric activity along the chromosomes. The eukaryotic organisms that present this type of chromosomes have been relatively understudied despite they constitute rather diversified species lineages. On the one hand, holocentric chromosomes may present intrinsic benefits (chromosome mutations such as fissions and fusions are potentially neutral in holocentrics). On the other hand, they present restrictions to the spatial separation of the functions of recombination and segregation during meiotic divisions (functions that may interfere), separation that is found in monocentric chromosomes. In this study, we compare the diversification rates of all known holocentric lineages in animals and plants with their most related monocentric lineages in order to elucidate whether holocentric chromosomes constitute an evolutionary advantage in terms of diversification and species richness. The results showed that null hypothesis of equal mean diversification rates cannot be rejected, leading us to surmise that shifts in diversification rates between holocentric and monocentric lineages might be due to other factors, such as the idiosyncrasy of each lineage or the interplay of evolutionary selections with the benefits of having either monocentric or holocentric chromosomes.

Acute leukemias of ambiguous lineage.

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Béné, Marie C; Porwit, Anna

2012-02-01

The 2008 edition of the WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues recognizes a special category called "leukemias of ambiguous lineage." The vast majority of these rare leukemias are classified as mixed phenotype acute leukemia (MPAL), although acute undifferentiated leukemias and natural killer lymphoblastic leukemias are also included. The major immunophenotypic markers used by the WHO 2008 to determine the lineage for these proliferations are myeloperoxidase, CD19, and cytoplasmic CD3. However, extensive immunophenotyping is necessary to confirm that the cells indeed belong to 2 different lineages or coexpress differentiation antigens of more than 1 lineage. Specific subsets of MPAL are defined by chromosomal anomalies such as the t(9;22) Philadelphia chromosome BCR-ABL1 or involvement of the MLL gene on chromosome 11q23. Other MPAL are divided into B/myeloid NOS, T/myeloid NOS, B/T NOS, and B/T/myeloid NOS. MPAL are usually of dire prognosis, respond variably to chemotherapy of acute lymphoblastic or acute myeloblastic type, and benefit most from rapid allogeneic hematopoietic stem cell transplantation.

Circumpolar diversity and geographic differentiation of mtDNA in the critically endangered Antarctic blue whale (Balaenoptera musculus intermedia.

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Angela L Sremba

Full Text Available The Antarctic blue whale (Balaenoptera musculus intermedia was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131° longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86 have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968±0.004, perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F(ST = 0.032, p<0.005 and microsatellite alleles (F(ST = 0.005, p<0.05 among the six Antarctic Areas historically used by the IWC for management of blue whales.

Comparative mtDNA phylogeography of neotropical freshwater fishes: testing shared history to infer the evolutionary landscape of lower Central America.

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Bermingham, E; Martin, A P

1998-04-01

Historical biogeography seeks to explain contemporary distributions of taxa in the context of intrinsic biological and extrinsic geological and climatic factors. To decipher the relative importance of biological characteristics vs. environmental conditions, it is necessary to ask whether groups of taxa with similar distributions share the same history of diversification. Because all of the taxa will have shared the same climatic and geological history, evidence of shared history across multiple species provides an estimate of the role of extrinsic factors in shaping contemporary biogeographic patterns. Similarly, differences in the records of evolutionary history across species will probably be signatures of biological differences. In this study, we focus on inferring the evolutionary history for geographical populations and closely related species representing three genera of primary freshwater fishes that are widely distributed in lower Central America (LCA) and northwestern Colombia. Analysis of mitochondrial gene trees provides the opportunity for robust tests of shared history across taxa. Moreover, because mtDNA permits inference of the temporal scale of diversification we can test hypotheses regarding the chronological development of the Isthmian corridor linking North and South America. We have focused attention on two issues. First, we show that many of the distinct populations of LCA fishes diverged in a relatively brief period of time thus limiting the phylogenetic signal available for tests of shared history. Second, our results provide reduced evidence of shared history when all drainages are included in the analysis because of inferred dispersion events that obscure the evolutionary history among drainage basins. When we restrict the analysis to areas that harbour endemic mitochondrial lineages, there is evidence of shared history across taxa. We hypothesize that there were two to three distinct waves of invasion into LCA from putative source

Somatic mtDNA mutation spectra in the aging human putamen.

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Siôn L Williams

Full Text Available The accumulation of heteroplasmic mitochondrial DNA (mtDNA deletions and single nucleotide variants (SNVs is a well-accepted facet of the biology of aging, yet comprehensive mutation spectra have not been described. To address this, we have used next generation sequencing of mtDNA-enriched libraries (Mito-Seq to investigate mtDNA mutation spectra of putamen from young and aged donors. Frequencies of the "common" deletion and other "major arc" deletions were significantly increased in the aged cohort with the fold increase in the frequency of the common deletion exceeding that of major arc deletions. SNVs also increased with age with the highest rate of accumulation in the non-coding control region which contains elements necessary for translation and replication. Examination of predicted amino acid changes revealed a skew towards pathogenic SNVs in the coding region driven by mutation bias. Levels of the pathogenic m.3243A>G tRNA mutation were also found to increase with age. Novel multimeric tandem duplications that resemble murine control region multimers and yeast ρ(- mtDNAs, were identified in both young and aged specimens. Clonal ∼50 bp deletions in the control region were found at high frequencies in aged specimens. Our results reveal the complex manner in which the mitochondrial genome alters with age and provides a foundation for studies of other tissues and disease states.

Identification of a PVL-negative SCCmec-IVa sub-lineage of the methicillin-resistant Staphylococcus aureus CC80 lineage

DEFF Research Database (Denmark)

Edslev, Sofie Marie; Westh, Henrik Torkil; Andersen, Paal Skytt

2018-01-01

of the CC80 S. aureus lineage was conducted from whole-genome sequences of 217 isolates (23 MSSA and 194 MRSA) from 22 countries. All isolates were further genetically characterized in regard to resistance determinants and PVL carriage, and epidemiological data was obtained for selected isolates. RESULTS....... CONCLUSIONS: This study reports the emergence of a novel CC80 CA-MRSA sub-lineage, showing that the CC80 lineage is more diverse than previously assumed....

Defects of mtDNA Replication Impaired Mitochondrial Biogenesis During Trypanosoma cruzi Infection in Human Cardiomyocytes and Chagasic Patients: The Role of Nrf1/2 and Antioxidant Response

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Wan, Xianxiu; Gupta, Shivali; Zago, Maria P.; Davidson, Mercy M.; Dousset, Pierre; Amoroso, Alejandro; Garg, Nisha Jain

2012-01-01

Background Mitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1)–regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease. Methods and Results We utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi–infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPARγ-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)–regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts. Conclusions The replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi–infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for

[Sequence polymorphism of mtDNA HVR Iand HVR II of Oroqen ethnic group in Inner Mongolia].

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Yan, Chun-Xia; Chen, Feng; Dang, Yong-Hui; Li, Tao; Zheng, Hai-Bo; Chen, Teng; Li, Sheng-Bin

2008-04-01

Venous blood samples from 50 unrelated Oroqen individuals living in Inner Mongolia were collected and their mtDNA HVR I and HVR II sequences were detected by using ABI PRISM377 sequencers. The number of polymorphic loci, haplotype, haplotype frequence, average nucleotide variability and other polymorphic parameters were calculated. Based on Oroqen mtDNA sequence data obtained in our experiments and published data, genetic distance between Oroqen ethnic group and other populations were computered by Nei's measure. Phylogenetic tree was constructed by Neighbor Joining method. Comparing with Anderson sequence, 52 polymorphic loci in HVR I and 24 loci in HVR II were found in Oroqen mtDNA sequence, 38 and 27 haplotypes were defined herewith. Haplotype diversity and average nucleotide variability were 0.964+/-0.018 and 7.379 in HVR I, 0.929+/-0.019 and 2.408 in HVR II respectively. Fst and dA genetic distance between 12 populations were calculated based on HVR I sequence, and their relative coefficients were 0.993(P HVR I and HVR II in Oroqen ethnic group has some specificities compared with that of other populations. These data provide a useful tool in forensic identification, population genetic study and other research fields.

Comparative mtDNA analyses of three sympatric macropodids from a conservation area on the Huon Peninsula, Papua New Guinea.

Science.gov (United States)

McGreevy, Thomas J; Dabek, Lisa; Husband, Thomas P

2016-07-01

Matschie's tree kangaroo (Dendrolagus matschiei), New Guinea pademelon (Thylogale browni), and small dorcopsis (Dorcopsulus vanheurni) are sympatric macropodid taxa, of conservation concern, that inhabit the Yopno-Urawa-Som (YUS) Conservation Area on the Huon Peninsula, Papua New Guinea. We sequenced three partial mitochondrial DNA (mtDNA) genes from the three taxa to (i) investigate network structure; and (ii) identify conservation units within the YUS Conservation Area. All three taxa displayed a similar pattern in the spatial distribution of their mtDNA haplotypes and the Urawa and Som rivers on the Huon may have acted as a barrier to maternal gene flow. Matschie's tree kangaroo and New Guinea pademelon within the YUS Conservation Area should be managed as single conservation units because mtDNA nucleotides were not fixed for a given geographic area. However, two distinct conservation units were identified for small dorcopsis from the two different mountain ranges within the YUS Conservation Area.

Analysis of mitochondrial DNA in Bolivian llama, alpaca and vicuna populations: a contribution to the phylogeny of the South American camelids.

Science.gov (United States)

Barreta, J; Gutiérrez-Gil, B; Iñiguez, V; Saavedra, V; Chiri, R; Latorre, E; Arranz, J J

2013-04-01

The objectives of this work were to assess the mtDNA diversity of Bolivian South American camelid (SAC) populations and to shed light on the evolutionary relationships between the Bolivian camelids and other populations of SACs. We have analysed two different mtDNA regions: the complete coding region of the MT-CYB gene and 513 bp of the D-loop region. The populations sampled included Bolivian llamas, alpacas and vicunas, and Chilean guanacos. High levels of genetic diversity were observed in the studied populations. In general, MT-CYB was more variable than D-loop. On a species level, the vicunas showed the lowest genetic variability, followed by the guanacos, alpacas and llamas. Phylogenetic analyses performed by including additional available mtDNA sequences from the studied species confirmed the existence of the two monophyletic clades previously described by other authors for guanacos (G) and vicunas (V). Significant levels of mtDNA hybridization were found in the domestic species. Our sequence analyses revealed significant sequence divergence within clade G, and some of the Bolivian llamas grouped with the majority of the southern guanacos. This finding supports the existence of more than the one llama domestication centre in South America previously suggested on the basis of archaeozoological evidence. Additionally, analysis of D-loop sequences revealed two new matrilineal lineages that are distinct from the previously reported G and V clades. The results presented here represent the first report on the population structure and genetic variability of Bolivian camelids and may help to elucidate the complex and dynamic domestication process of SAC populations. © 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.

Targeted transgenic overexpression of mitochondrial thymidine kinase (TK2) alters mitochondrial DNA (mtDNA) and mitochondrial polypeptide abundance: transgenic TK2, mtDNA, and antiretrovirals.

Science.gov (United States)

Hosseini, Seyed H; Kohler, James J; Haase, Chad P; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

2007-03-01

Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-gamma. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK1) were used to study NRTI mitochondrial toxicity. Echocardiography and nuclear magnetic resonance imaging defined cardiac performance and structure. TK gene copy and enzyme activity, mitochondrial (mt) DNA and polypeptide abundance, succinate dehydrogenase and cytochrome oxidase histochemistry, and electron microscopy correlated with transgenesis, mitochondrial structure, and biogenesis. Antiretroviral combinations simulated therapy. Untreated hTK1 or TK2 TGs exhibited normal left ventricle mass. In TK2 TGs, cardiac TK2 gene copy doubled, activity increased 300-fold, and mtDNA abundance doubled. Abundance of the 17-kd subunit of complex I, succinate dehydrogenase histochemical activity, and cristae density increased. NRTIs increased left ventricle mass 20% in TK2 TGs. TK activity increased 3 logs in hTK1 TGs, but no cardiac phenotype resulted. NRTIs abrogated functional effects of transgenically increased TK2 activity but had no effect on TK2 mtDNA abundance. Thus, NRTI mitochondrial phosphorylation by TK2 is integral to clinical NRTI mitochondrial toxicity.

In search of the genetic footprints of Sumerians: a survey of Y-chromosome and mtDNA variation in the Marsh Arabs of Iraq

Directory of Open Access Journals (Sweden)

Olivieri Anna

2011-10-01

Full Text Available Abstract Background For millennia, the southern part of the Mesopotamia has been a wetland region generated by the Tigris and Euphrates rivers before flowing into the Gulf. This area has been occupied by human communities since ancient times and the present-day inhabitants, the Marsh Arabs, are considered the population with the strongest link to ancient Sumerians. Popular tradition, however, considers the Marsh Arabs as a foreign group, of unknown origin, which arrived in the marshlands when the rearing of water buffalo was introduced to the region. Results To shed some light on the paternal and maternal origin of this population, Y chromosome and mitochondrial DNA (mtDNA variation was surveyed in 143 Marsh Arabs and in a large sample of Iraqi controls. Analyses of the haplogroups and sub-haplogroups observed in the Marsh Arabs revealed a prevalent autochthonous Middle Eastern component for both male and female gene pools, with weak South-West Asian and African contributions, more evident in mtDNA. A higher male than female homogeneity is characteristic of the Marsh Arab gene pool, likely due to a strong male genetic drift determined by socio-cultural factors (patrilocality, polygamy, unequal male and female migration rates. Conclusions Evidence of genetic stratification ascribable to the Sumerian development was provided by the Y-chromosome data where the J1-Page08 branch reveals a local expansion, almost contemporary with the Sumerian City State period that characterized Southern Mesopotamia. On the other hand, a more ancient background shared with Northern Mesopotamia is revealed by the less represented Y-chromosome lineage J1-M267*. Overall our results indicate that the introduction of water buffalo breeding and rice farming, most likely from the Indian sub-continent, only marginally affected the gene pool of autochthonous people of the region. Furthermore, a prevalent Middle Eastern ancestry of the modern population of the marshes of

The extremely divergent maternally- and paternally-transmitted mitochondrial genomes are co-expressed in somatic tissues of two freshwater mussel species with doubly uniparental inheritance of mtDNA

Science.gov (United States)

Breton, Sophie; Bouvet, Karim; Auclair, Gabrielle; Ghazal, Stephanie; Sietman, Bernard E.; Johnson, Nathan A.; Bettinazzi, Stefano; Dtewart, Donald T.; Guerra, Davide

2017-01-01

Freshwater mussel species with doubly uniparental inheritance (DUI) of mtDNA are unique because they are naturally heteroplasmic for two extremely divergent mtDNAs with ~50% amino acid differences for protein-coding genes. The paternally-transmitted mtDNA (or M mtDNA) clearly functions in sperm in these species, but it is still unknown whether it is transcribed when present in male or female soma. In the present study, we used PCR and RT-PCR to detect the presence and expression of the M mtDNA in male and female somatic and gonadal tissues of the freshwater mussel species Venustaconcha ellipsiformis and Utterbackia peninsularis (Unionidae). This is the first study demonstrating that the M mtDNA is transcribed not only in male gonads, but also in male and female soma in freshwater mussels with DUI. Because of the potentially deleterious nature of heteroplasmy, we suggest the existence of different mechanisms in DUI species to deal with this possibly harmful situation, such as silencing mechanisms for the M mtDNA at the transcriptional, post-transcriptional and/or post-translational levels. These hypotheses will necessitate additional studies in distantly-related DUI species that could possess different mechanisms of action to deal with heteroplasmy.

Heterozygous SSBP1 start loss mutation co-segregates with hearing loss and the m.1555A>G mtDNA variant in a large multigenerational family.

Science.gov (United States)

Kullar, Peter J; Gomez-Duran, Aurora; Gammage, Payam A; Garone, Caterina; Minczuk, Michal; Golder, Zoe; Wilson, Janet; Montoya, Julio; Häkli, Sanna; Kärppä, Mikko; Horvath, Rita; Majamaa, Kari; Chinnery, Patrick F

2018-01-01

The m.1555A>G mtDNA variant causes maternally inherited deafness, but the reasons for the highly variable clinical penetrance are not known. Exome sequencing identified a heterozygous start loss mutation in SSBP1, encoding the single stranded binding protein 1 (SSBP1), segregating with hearing loss in a multi-generational family transmitting m.1555A>G, associated with mtDNA depletion and multiple deletions in skeletal muscle. The SSBP1 mutation reduced steady state SSBP1 levels leading to a perturbation of mtDNA metabolism, likely compounding the intra-mitochondrial translation defect due to m.1555A>G in a tissue-specific manner. This family demonstrates the importance of rare trans-acting genetic nuclear modifiers in the clinical expression of mtDNA disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

A new mitochondrial C1 lineage from the prehistory of Uruguay: population genocide, ethnocide, and continuity.

Science.gov (United States)

Sans, Monica; Figueiro, Gonzalo; Hidalgo, Pedro C

2012-06-01

Uruguayan population has been considered as of European descent, as its Native populations victims of genocide apparently disappeared in the 19th century. Contradicting this national belief, genetic studies have shown a substantial Native contribution. However, the continuity between prehistoric, historic, and present populations remains unproved. With the aim of adding elements to prove a possible population continuity, we studied a mitochondrial lineage, part of haplogroup C1, analyzing the complete genome of a modern Uruguayan individual and the hypervariable region I (HVRI) in prehistoric, historic, and contemporary individuals. Several individuals carried the mutations that characterize this lineage: two from an archaeological mound located in the east of the country, the Charrúa Indian chief Vaimaca Perú and five individuals from the present population. The lineage was initially characterized by its HVRI sequence, having the four typical C1 mutations and adding 16051G and 16288C; other mutations were also found: 16140C was found in all but the oldest individual, dated 1,610 years BP, while 16209C, 16422C, and 16519C were found only in some individuals. Hypervariable region II showed the typical C1 mutations and 194T. The coding region, analyzed in modern individuals, was characterized by 12378T, while other mutations found were not common to all of them. In summary, we have found and described a new lineage that shows continuity from prehistoric mound builders to the present population, through a representative of the extinct Charrúa Indians. The lineage appeared at least 1,600 years ago and is carried by approximately 0.7% of the modern Uruguayan population. The continuity of the lineage supports alternative perspectives about Uruguayan national identity and the meaning of the genocide, best labeled as ethnocide because of its consequences. It also contributes to the discussion about who the prehistoric mound builders were, and to the origin, at least in

Instruction of hematopoietic lineage choice by cytokine signaling

Energy Technology Data Exchange (ETDEWEB)

Endele, Max; Etzrodt, Martin; Schroeder, Timm, E-mail: timm.schroeder@bsse.ethz.ch

2014-12-10

Hematopoiesis is the cumulative consequence of finely tuned signaling pathways activated through extrinsic factors, such as local niche signals and systemic hematopoietic cytokines. Whether extrinsic factors actively instruct the lineage choice of hematopoietic stem and progenitor cells or are only selectively allowing survival and proliferation of already intrinsically lineage-committed cells has been debated over decades. Recent results demonstrated that cytokines can instruct lineage choice. However, the precise function of individual cytokine-triggered signaling molecules in inducing cellular events like proliferation, lineage choice, and differentiation remains largely elusive. Signal transduction pathways activated by different cytokine receptors are highly overlapping, but support the production of distinct hematopoietic lineages. Cellular context, signaling dynamics, and the crosstalk of different signaling pathways determine the cellular response of a given extrinsic signal. New tools to manipulate and continuously quantify signaling events at the single cell level are therefore required to thoroughly interrogate how dynamic signaling networks yield a specific cellular response. - Highlights: • Recent studies provided definite proof for lineage-instructive action of cytokines. • Signaling pathways involved in hematopoietic lineage instruction remain elusive. • New tools are emerging to quantitatively study dynamic signaling networks over time.

A novel quantitative assay of mitophagy: Combining high content fluorescence microscopy and mitochondrial DNA load to quantify mitophagy and identify novel pharmacological tools against pathogenic heteroplasmic mtDNA.

Science.gov (United States)

Diot, Alan; Hinks-Roberts, Alex; Lodge, Tiffany; Liao, Chunyan; Dombi, Eszter; Morten, Karl; Brady, Stefen; Fratter, Carl; Carver, Janet; Muir, Rebecca; Davis, Ryan; Green, Charlotte J; Johnston, Iain; Hilton-Jones, David; Sue, Carolyn; Mortiboys, Heather; Poulton, Joanna

2015-10-01

Mitophagy is a cellular mechanism for the recycling of mitochondrial fragments. This process is able to improve mitochondrial DNA (mtDNA) quality in heteroplasmic mtDNA disease, in which mutant mtDNA co-exists with normal mtDNA. In disorders where the load of mutant mtDNA determines disease severity it is likely to be an important determinant of disease progression. Measuring mitophagy is technically demanding. We used pharmacological modulators of autophagy to validate two techniques for quantifying mitophagy. First we used the IN Cell 1000 analyzer to quantify mitochondrial co-localisation with LC3-II positive autophagosomes. Unlike conventional fluorescence and electron microscopy, this high-throughput system is sufficiently sensitive to detect transient low frequency autophagosomes. Secondly, because mitophagy preferentially removes pathogenic heteroplasmic mtDNA mutants, we developed a heteroplasmy assay based on loss of m.3243A>G mtDNA, during culture conditions requiring oxidative metabolism ("energetic stress"). The effects of the pharmacological modulators on these two measures were consistent, confirming that the high throughput imaging output (autophagosomes co-localising with mitochondria) reflects mitochondrial quality control. To further validate these methods, we performed a more detailed study using metformin, the most commonly prescribed antidiabetic drug that is still sometimes used in Maternally Inherited Diabetes and Deafness (MIDD). This confirmed our initial findings and revealed that metformin inhibits mitophagy at clinically relevant concentrations, suggesting that it may have novel therapeutic uses. Copyright © 2015. Published by Elsevier Ltd.

Heterogeneous periodicity of drosophila mtDNA: new refutations of neutral and nearly neutral evolution

Directory of Open Access Journals (Sweden)

Carlos Y Valenzuela

2011-01-01

Full Text Available We found a consistent 3-site periodicity of the X²9 values for the heterogeneity of the distribution of the second base in relation to the first base of dinucleotides separated by 0 (contiguous, 1, 2, 3 ... 17 (K nucleotide sites in Drosophila mtDNA. Triplets of X²9 values were found where the first was over 300 and the second and third ranged between 37 and 114 (previous studies. In this study, the periodicity was significant until separation of 2011K, and a structure of deviations from randomness among dinucleotides was found. The most deviant dinucleotides were G-G, G-C and C-G for the first, second and third element of the triplet, respectively. In these three cases there were more dinucleotides observed than expected. This inter-bases correlation and periodicity may be related to the tertiary structure of circular DNA, like that of prokaryotes and mitochondria, to protect and preserve it. The mtDNA with 19.517 bp was divided into four equal segments of 4.879 bp. The fourth sub-segment presented a very low proportion of G and C, the internucleotide interaction was weaker in this sub-segment and no periodicity was found. The maintenance of this mtDNA structure and organization for millions of generations, in spite of a high recurrent mutation rate, does not support the notion of neutralism or near neutralism. The high level of internucleotide interaction and periodicity indicate that every nucleotide is co-adapted with the residual genome.

Comprehensive view of the population history of Arabia as inferred by mtDNA variation

Czech Academy of Sciences Publication Activity Database

Černý, Viktor; Čížková, M.; Poloni, E. S.; Al-Meeri, A.; Mulligan, C. J.

2016-01-01

Roč. 159, č. 4 (2016), s. 607-616 ISSN 0002-9483 R&D Projects: GA ČR GA13-37998S Institutional support: RVO:67985912 Keywords : mtDNA variation * Arabian Peninsula * migrations Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.552, year: 2016

Recent introgressive hybridization revealed by exclusive mtDNA transfer from Oreochromis leucostictus (Trewavas, 1933) to Oreochromis niloticus (Linnaeus, 1758) in Lake Baringo, Kenya

OpenAIRE

Nyingi, Dorothy W.; Agnèse, Jean-François

2007-01-01

Nuclear DNA and mtDNA polymorphisms were surveyed in various species of East African Oreochromis. In Lake Baringo, where only Oreochromis niloticus baringoensis is present, alien mtDNA haplotypes were observed, apparently the result of introgressive hybridization with Oreochromis leucostictus. This introgression is not accompanied by any substantial or recorded transfer of nuclear genes into O. n. baringoensis.

MtDNA genomes reveal a relaxation of selective constraints in low-BMI individuals in a Uyghur population.

Science.gov (United States)

Zheng, Hong-Xiang; Li, Lei; Jiang, Xiao-Yan; Yan, Shi; Qin, Zhendong; Wang, Xiaofeng; Jin, Li

2017-10-01

Considerable attention has been focused on the effect of deleterious mutations caused by the recent relaxation of selective constraints on human health, including the prevalence of obesity, which might represent an adaptive response of energy-conserving metabolism under the conditions of modern society. Mitochondrial DNA (mtDNA) encoding 13 core subunits of oxidative phosphorylation plays an important role in metabolism. Therefore, we hypothesized that a relaxation of selection constraints on mtDNA and an increase in the proportion of deleterious mutations have played a role in obesity prevalence. In this study, we collected and sequenced the mtDNA genomes of 722 Uyghurs, a typical population with a high prevalence of obesity. We identified the variants that occurred in the Uyghur population for each sample and found that the number of nonsynonymous mutations carried by Uyghur individuals declined with elevation of their BMI (P = 0.015). We further calculated the nonsynonymous and synonymous ratio (N/S) of the high-BMI and low-BMI haplogroups, and the results showed that a significantly higher N/S occurred in the whole mtDNA genomes of the low-BMI haplogroups (0.64) than in that of the high-BMI haplogroups (0.35, P = 0.030) and ancestor haplotypes (0.41, P = 0.032); these findings indicated that low-BMI individuals showed a recent relaxation of selective constraints. In addition, we investigated six clinical characteristics and found that fasting plasma glucose might be correlated with the N/S and selective pressures. We hypothesized that a higher proportion of deleterious mutations led to mild mitochondrial dysfunction, which helps to drive glucose consumption and thereby prevents obesity. Our results provide new insights into the relationship between obesity predisposition and mitochondrial genome evolution.

Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

Energy Technology Data Exchange (ETDEWEB)

Jiang, Zhenzhou, E-mail: jiangcpu@yahoo.com.cn; Bao, Qingli, E-mail: bao_ql@126.com; Sun, Lixin, E-mail: slxcpu@126.com; Huang, Xin, E-mail: huangxinhx66@sohu.com; Wang, Tao, E-mail: wangtao1331@126.com; Zhang, Shuang, E-mail: cat921@sina.com; Li, Han, E-mail: hapo1101@163.com; Zhang, Luyong, E-mail: lyzhang@cpu.edu.cn

2013-01-15

This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

The Expansion of mtDNA Haplogroup L3 within and out of Africa

Czech Academy of Sciences Publication Activity Database

Soares, P.; Alshamali, F.; Pereira, J. B.; Fernandes, V.; Silva, N. M.; Afonso, C.; Costa, M. D.; Musilová, E.; Macaulay, V.; Richards, M. B.; Černý, Viktor; Pereira, L.

2012-01-01

Roč. 29, č. 3 (2012), s. 915-927 ISSN 0737-4038 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA * complete genomes * haplogroup L3 * out of Africa * modern human expansions Sub ject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 10.353, year: 2012

Behavioral vs. molecular sources of conflict between nuclear and mitochondrial DNA: The role of male-biased dispersal in a Holarctic sea duck

Science.gov (United States)

Peters, Jeffrey L.; Bolender, Kimberly A.; Pearce, John M.

2012-01-01

Genetic studies of waterfowl (Anatidae) have observed the full spectrum of mitochondrial (mt) DNA population divergence, from apparent panmixia to deep, reciprocally monophyletic lineages. Yet, these studies often found weak or no nuclear (nu) DNA structure, which was often attributed to male-biased gene flow, a common behaviour within this family. An alternative explanation for this ‘conflict’ is that the smaller effective population size and faster sorting rate of mtDNA relative to nuDNA lead to different signals of population structure. We tested these alternatives by sequencing 12 nuDNA introns for a Holarctic pair of waterfowl subspecies, the European goosander (Mergus merganser merganser) and the North American common merganser (M. m. americanus), which exhibit strong population structure in mtDNA. We inferred effective population sizes, gene flow and divergence times from published mtDNA sequences and simulated expected differentiation for nuDNA based on those histories. Between Europe and North America, nuDNA ФST was 3.4-fold lower than mtDNA ФST, a result consistent with differences in sorting rates. However, despite geographically structured and monophyletic mtDNA lineages within continents, nuDNA ФST values were generally zero and significantly lower than predicted. This between- and within-continent contrast held when comparing mtDNA and nuDNA among published studies of ducks. Thus, male-mediated gene flow is a better explanation than slower sorting rates for limited nuDNA differentiation within continents, which is also supported by nonmolecular data. This study illustrates the value of quantitatively testing discrepancies between mtDNA and nuDNA to reject the null hypothesis that conflict simply reflects different sorting rates.

Pleistocene-Holocene boundary in Southern Arabia from the perspective of human mtDNA variation

Czech Academy of Sciences Publication Activity Database

Al-Abri, A.-R.; Podgorná, E.; Rose, J. I.; Pereira, L.; Mulligan, C. J.; Silva, N. M.; Bayoumi, R.; Soares, P.; Černý, Viktor

2012-01-01

Roč. 149, č. 2 (2012), s. 291-298 ISSN 0002-9483 R&D Projects: GA MŠk ME 917 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA variation * Arabian Peninsula * migrations Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 2.481, year: 2012

Malware Lineage in the Wild

OpenAIRE

Haq, Irfan Ul; Chica, Sergio; Caballero, Juan; Jha, Somesh

2017-01-01

Malware lineage studies the evolutionary relationships among malware and has important applications for malware analysis. A persistent limitation of prior malware lineage approaches is to consider every input sample a separate malware version. This is problematic since a majority of malware are packed and the packing process produces many polymorphic variants (i.e., executables with different file hash) of the same malware version. Thus, many samples correspond to the same malware version and...

Mitochondrial DNA heritage of Cres Islanders--example of Croatian genetic outliers.

Science.gov (United States)

Jeran, Nina; Havas Augustin, Dubravka; Grahovac, Blaienka; Kapović, Miljenko; Metspalu, Ene; Villems, Richard; Rudan, Pavao

2009-12-01

Diversity of mitochondrial DNA (mtDNA) lineages of the Island of Cres was determined by high-resolution phylogenetic analysis on a sample of 119 adult unrelated individuals from eight settlements. The composition of mtDNA pool of this Island population is in contrast with other Croatian and European populations. The analysis revealed the highest frequency of haplogroup U (29.4%) with the predominance of one single lineage of subhaplogroup U2e (20.2%). Haplogroup H is the second most prevalent one with only 27.7%. Other very interesting features of contemporary Island population are extremely low frequency of haplogroup J (only 0.84%), and much higher frequency of haplogroup W (12.6%) comparing to other Croatian and European populations. Especially interesting finding is a strikingly higher frequency of haplogroup N1a (9.24%) presented with African/south Asian branch almost absent in Europeans, while its European sister-branch, proved to be highly prevalent among Neolithic farmers, is present in contemporary Europeans with only 0.2%. Haplotype analysis revealed that only five mtDNA lineages account for almost 50% of maternal genetic heritage of this island and they present supposed founder lineages. All presented findings confirm that genetic drift, especially founder effect, has played significant role in shaping genetic composition of the isolated population of the Island of Cres. Due to presented data contemporary population of Cres Island can be considered as genetic "outlier" among Croatian populations.

Molecular genetic differentiation in earthworms inhabiting a heterogeneous Pb-polluted landscape

International Nuclear Information System (INIS)

Andre, J.; King, R.A.; Stuerzenbaum, S.R.; Kille, P.; Hodson, M.E.; Morgan, A.J.

2010-01-01

A Pb-mine site situated on acidic soil, but comprising of Ca-enriched islands around derelict buildings was used to study the spatial pattern of genetic diversity in Lumbricus rubellus. Two distinct genetic lineages ('A' and 'B'), differentiated at both the mitochondrial (mtDNA COII) and nuclear level (AFLPs) were revealed with a mean inter-lineage mtDNA sequence divergence of approximately 13%, indicative of a cryptic species complex. AFLP analysis indicates that lineage A individuals within one central 'ecological island' site are uniquely clustered, with little genetic overlap with lineage A individuals at the two peripheral sites. FTIR microspectroscopy of Pb-sequestering chloragocytes revealed different phosphate profiles in residents of adjacent acidic and calcareous islands. Bioinformatics found over-representation of Ca pathway genes in EST Pb libraries. Subsequent sequencing of a Ca-transport gene, SERCA, revealed mutations in the protein's cytosolic domain. We recommend the mandatory genotyping of all individuals prior to field-based ecotoxicological assays, particularly those using discriminating genomic technologies. - Landscapes punctuated by Pb-polluted islands have engendered local genetic differentiation in resident earthworms.

Lineage Selection and the Maintenance of Sex

Science.gov (United States)

de Vienne, Damien M.; Giraud, Tatiana; Gouyon, Pierre-Henri

2013-01-01

Sex predominates in eukaryotes, despite its short-term disadvantage when compared to asexuality. Myriad models have suggested that short-term advantages of sex may be sufficient to counterbalance its twofold costs. However, despite decades of experimental work seeking such evidence, no evolutionary mechanism has yet achieved broad recognition as explanation for the maintenance of sex. We explore here, through lineage-selection models, the conditions favouring the maintenance of sex. In the first model, we allowed the rate of transition to asexuality to evolve, to determine whether lineage selection favoured species with the strongest constraints preventing the loss of sex. In the second model, we simulated more explicitly the mechanisms underlying the higher extinction rates of asexual lineages than of their sexual counterparts. We linked extinction rates to the ecological and/or genetic features of lineages, thereby providing a formalisation of the only figure included in Darwin's “The origin of species”. Our results reinforce the view that the long-term advantages of sex and lineage selection may provide the most satisfactory explanations for the maintenance of sex in eukaryotes, which is still poorly recognized, and provide figures and a simulation website for training and educational purposes. Short-term benefits may play a role, but it is also essential to take into account the selection of lineages for a thorough understanding of the maintenance of sex. PMID:23825582

Identification and Characterization of Mouse Otic Sensory Lineage Genes

Directory of Open Access Journals (Sweden)

Byron H. Hartman

2015-03-01

Full Text Available Vertebrate embryogenesis gives rise to all cell types of an organism through the development of many unique lineages derived from the three primordial germ layers. The otic sensory lineage arises from the otic vesicle, a structure formed through invagination of placodal non-neural ectoderm. This developmental lineage possesses unique differentiation potential, giving rise to otic sensory cell populations including hair cells, supporting cells, and ganglion neurons of the auditory and vestibular organs. Here we present a systematic approach to identify transcriptional features that distinguish the otic sensory lineage (from early otic progenitors to otic sensory populations from other major lineages of vertebrate development. We used a microarray approach to analyze otic sensory lineage populations including microdissected otic vesicles (embryonic day 10.5 as well as isolated neonatal cochlear hair cells and supporting cells at postnatal day 3. Non-otic tissue samples including periotic tissues and whole embryos with otic regions removed were used as reference populations to evaluate otic specificity. Otic populations shared transcriptome-wide correlations in expression profiles that distinguish members of this lineage from non-otic populations. We further analyzed the microarray data using comparative and dimension reduction methods to identify individual genes that are specifically expressed in the otic sensory lineage. This analysis identified and ranked top otic sensory lineage-specific transcripts including Fbxo2, Col9a2, and Oc90, and additional novel otic lineage markers. To validate these results we performed expression analysis on select genes using immunohistochemistry and in situ hybridization. Fbxo2 showed the most striking pattern of specificity to the otic sensory lineage, including robust expression in the early otic vesicle and sustained expression in prosensory progenitors and auditory and vestibular hair cells and supporting

Early diversification trend and Asian origin for extent bat lineages.

Science.gov (United States)

Yu, W; Wu, Y; Yang, G

2014-10-01

Bats are a unique mammalian group, which belong to one of the largest and most diverse mammalian radiations, but their early diversification is still poorly understood, and conflicting hypotheses have emerged regarding their biogeographic history. Understanding their diversification is crucial for untangling the enigmatic evolutionary history of bats. In this study, we elucidated the rate of diversification and the biogeographic history of extant bat lineages using genus-level chronograms. The results suggest that a rapid adaptive radiation persisted from the emergence of crown bats until the Early Eocene Climatic Optimum, whereas there was a major deceleration in diversification around 35-49 Ma. There was a positive association between changes in the palaeotemperature and the net diversification rate until 35 Ma, which suggests that the palaeotemperature may have played an important role in the regulation of ecological opportunities. By contrast, there were unexpectedly higher diversification rates around 25-35 Ma during a period characterized by intense and long-lasting global cooling, which implies that intrinsic innovations or adaptations may have released some lineages from the intense selective pressures associated with these severe conditions. Our reconstruction of the ancestral distribution suggests an Asian origin for bats, thereby indicating that the current panglobal but disjunct distribution pattern of extant bats may be related to events involving seriate cross-continental dispersal and local extinction, as well as the influence of geological events and the expansion and contraction of megathermal rainforests during the Tertiary. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

The Korarchaeota: Archaeal orphans representing an ancestral lineage of life

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Elkins, James G.; Kunin, Victor; Anderson, Iain; Barry, Kerrie; Goltsman, Eugene; Lapidus, Alla; Hedlund, Brian; Hugenholtz, Phil; Kyrpides, Nikos; Graham, David; Keller, Martin; Wanner, Gerhard; Richardson, Paul; Stetter, Karl O.

2007-05-01

Based on conserved cellular properties, all life on Earth can be grouped into different phyla which belong to the primary domains Bacteria, Archaea, and Eukarya. However, tracing back their evolutionary relationships has been impeded by horizontal gene transfer and gene loss. Within the Archaea, the kingdoms Crenarchaeota and Euryarchaeota exhibit a profound divergence. In order to elucidate the evolution of these two major kingdoms, representatives of more deeply diverged lineages would be required. Based on their environmental small subunit ribosomal (ss RNA) sequences, the Korarchaeota had been originally suggested to have an ancestral relationship to all known Archaea although this assessment has been refuted. Here we describe the cultivation and initial characterization of the first member of the Korarchaeota, highly unusual, ultrathin filamentous cells about 0.16 {micro}m in diameter. A complete genome sequence obtained from enrichment cultures revealed an unprecedented combination of signature genes which were thought to be characteristic of either the Crenarchaeota, Euryarchaeota, or Eukarya. Cell division appears to be mediated through a FtsZ-dependent mechanism which is highly conserved throughout the Bacteria and Euryarchaeota. An rpb8 subunit of the DNA-dependent RNA polymerase was identified which is absent from other Archaea and has been described as a eukaryotic signature gene. In addition, the representative organism possesses a ribosome structure typical for members of the Crenarchaeota. Based on its gene complement, this lineage likely diverged near the separation of the two major kingdoms of Archaea. Further investigations of these unique organisms may shed additional light onto the evolution of extant life.

mtDNA of Fulani Nomads and Their Genetic Relationships to Neighboring Sedentary Populations

Czech Academy of Sciences Publication Activity Database

Černý, Viktor; Hájek, Martin; Bromová, Markéta; Čmejla, R.; Diallo, I.; Brdička, R.

2006-01-01

Roč. 78, č. 1 (2006), s. 9-27 ISSN 0018-7143 R&D Projects: GA ČR(CZ) GA404/03/0318 Institutional research plan: CEZ:AV0Z80020508 Keywords : mtDNA variation * HVS-I * Fulani nomads * sub-Saharan populations * Chad * Cameroon * Burkina Faso Subject RIV: AC - Archeology, Anthropology, Ethnology Impact factor: 1.132, year: 2006

Lineage-specific serology confirms Brazilian Atlantic forest lion tamarins, Leontopithecus chrysomelas and Leontopithecus rosalia, as reservoir hosts of Trypanosoma cruzi II (TcII

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Charlotte L. Kerr

2016-11-01

Full Text Available Abstract Background Trypanosoma cruzi, the agent of Chagas disease in humans, has a vast reservoir of mammalian hosts in the Americas, and is classified into six genetic lineages, TcI-TcVI, with a possible seventh, TcBat. Elucidating enzootic cycles of the different lineages is important for understanding the ecology of this parasite, the emergence of new outbreaks of Chagas disease and for guiding control strategies. Direct lineage identification by genotyping is hampered by limitations of parasite isolation and culture. An indirect method is to identify lineage-specific serological reactions in infected individuals; here we describe its application with sylvatic Brazilian primates. Methods Synthetic peptides representing lineage-specific epitopes of the T. cruzi surface protein TSSA were used in ELISA with sera from Atlantic Forest Leontopithecus chrysomelas (golden-headed lion tamarin, L. rosalia (golden lion tamarin, Amazonian Sapajus libidinosus (black-striped capuchin and Alouatta belzebul (red-handed howler monkey. Results The epitope common to lineages TcII, TcV and TcVI was recognised by sera from 15 of 26 L. chrysomelas and 8 of 13 L. rosalia. For 12 of these serologically identified TcII infections, the identity of the lineage infection was confirmed by genotyping T. cruzi isolates. Of the TcII/TcV/TcVI positive sera 12 of the 15 L. chrysomelas and 2 of the 8 L. rosalia also reacted with the specific epitope restricted to TcV and TcVI. Sera from one of six S. libidinous recognised the TcIV/TcIII epitopes. Conclusions This lineage-specific serological surveillance has verified that Atlantic Forest primates are reservoir hosts of at least TcII, and probably TcV and TcVI, commonly associated with severe Chagas disease in the southern cone region of South America. With appropriate reagents, this novel methodology is readily applicable to a wide range of mammal species and reservoir host discovery.

Lineage fusion in Galápagos giant tortoises.

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Garrick, Ryan C; Benavides, Edgar; Russello, Michael A; Hyseni, Chaz; Edwards, Danielle L; Gibbs, James P; Tapia, Washington; Ciofi, Claudio; Caccone, Adalgisa

2014-11-01

Although many classic radiations on islands are thought to be the result of repeated lineage splitting, the role of past fusion is rarely known because during these events, purebreds are rapidly replaced by a swarm of admixed individuals. Here, we capture lineage fusion in action in a Galápagos giant tortoise species, Chelonoidis becki, from Wolf Volcano (Isabela Island). The long generation time of Galápagos tortoises and dense sampling (841 individuals) of genetic and demographic data were integral in detecting and characterizing this phenomenon. In C. becki, we identified two genetically distinct, morphologically cryptic lineages. Historical reconstructions show that they colonized Wolf Volcano from Santiago Island in two temporally separated events, the first estimated to have occurred ~199 000 years ago. Following arrival of the second wave of colonists, both lineages coexisted for approximately ~53 000 years. Within that time, they began fusing back together, as microsatellite data reveal widespread introgressive hybridization. Interestingly, greater mate selectivity seems to be exhibited by purebred females of one of the lineages. Forward-in-time simulations predict rapid extinction of the early arriving lineage. This study provides a rare example of reticulate evolution in action and underscores the power of population genetics for understanding the past, present and future consequences of evolutionary phenomena associated with lineage fusion. © 2014 John Wiley & Sons Ltd.

Linking the sub-Saharan and West Eurasian gene pools: maternal and paternal heritage of the Tuareg nomads from the African Sahel.

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Pereira, Luísa; Cerný, Viktor; Cerezo, María; Silva, Nuno M; Hájek, Martin; Vasíková, Alzbeta; Kujanová, Martina; Brdicka, Radim; Salas, Antonio

2010-08-01

The Tuareg presently live in the Sahara and the Sahel. Their ancestors are commonly believed to be the Garamantes of the Libyan Fezzan, ever since it was suggested by authors of antiquity. Biological evidence, based on classical genetic markers, however, indicates kinship with the Beja of Eastern Sudan. Our study of mitochondrial DNA (mtDNA) sequences and Y chromosome SNPs of three different southern Tuareg groups from Mali, Burkina Faso and the Republic of Niger reveals a West Eurasian-North African composition of their gene pool. The data show that certain genetic lineages could not have been introduced into this population earlier than approximately 9000 years ago whereas local expansions establish a minimal date at around 3000 years ago. Some of the mtDNA haplogroups observed in the Tuareg population were involved in the post-Last Glacial Maximum human expansion from Iberian refugia towards both Europe and North Africa. Interestingly, no Near Eastern mtDNA lineages connected with the Neolithic expansion have been observed in our population sample. On the other hand, the Y chromosome SNPs data show that the paternal lineages can very probably be traced to the Near Eastern Neolithic demic expansion towards North Africa, a period that is otherwise concordant with the above-mentioned mtDNA expansion. The time frame for the migration of the Tuareg towards the African Sahel belt overlaps that of early Holocene climatic changes across the Sahara (from the optimal greening approximately 10 000 YBP to the extant aridity beginning at approximately 6000 YBP) and the migrations of other African nomadic peoples in the area.

Reconstruction of major maternal and paternal lineages of the Cape Muslim population

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Shafieka Isaacs

2013-01-01

Full Text Available The earliest Cape Muslims were brought to the Cape (Cape Town -South Africa from Africa and Asia from 1652 to 1834. They were part of an involuntary migration of slaves, political prisoners and convicts, and they contributed to the ethnic diversity of the present Cape Muslim population of South Africa. The history of the Cape Muslims has been well documented and researched however no in-depth genetic studies have been undertaken. The aim of the present study was to determine the respective African, Asian and European contributions to the mtDNA (maternal and Y-chromosomal (paternal gene pool of the Cape Muslim population, by analyzing DNA samples of 100 unrelated Muslim males born in the Cape Metropolitan area. A panel of six mtDNA and eight Y-chromosome SNP markers were screened using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP. Overall admixture estimates for the maternal line indicated Asian (0.4168 and African mtDNA (0.4005 as the main contributors. The admixture estimates for the paternal line, however, showed a predominance of the Asian contribution (0.7852. The findings are in accordance with historical data on the origins of the early Cape Muslims.

Contrasting microsatellite diversity in the evolutionary lineages of Phytophthora lateralis.

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Vettraino, AnnaMaria; Brasier, Clive M; Webber, Joan F; Hansen, Everett M; Green, Sarah; Robin, Cecile; Tomassini, Alessia; Bruni, Natalia; Vannini, Andrea

2017-02-01

Following recent discovery of Phytophthora lateralis on native Chamaecyparis obtusa in Taiwan, four phenotypically distinct lineages were discriminated: the Taiwan J (TWJ) and Taiwan K (TWK) in Taiwan, the Pacific Northwest (PNW) in North America and Europe and the UK in west Scotland. Across the four lineages, we analysed 88 isolates from multiple sites for microsatellite diversity. Twenty-one multilocus genotypes (MLGs) were resolved with high levels of diversity of the TWK and PNW lineages. No alleles were shared between the PNW and the Taiwanese lineages. TWK was heterozygous at three loci, whereas TWJ isolates were homozygous apart from one isolate, which exhibited a unique allele also present in the TWK lineage. PNW lineage was heterozygous at three loci. The evidence suggests its origin may be a yet unknown Asian source. North American and European PNW isolates shared all their alleles and also a dominant MLG, consistent with a previous proposal that this lineage is a recent introduction into Europe from North America. The UK lineage was monomorphic and homozygous at all loci. It shared its alleles with the PNW and the TWJ and TWK lineages, hence a possible origin in a recent hybridisation event between a Taiwan lineage and PNW cannot be ruled out. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Human Retinal Transmitochondrial Cybrids with J or H mtDNA Haplogroups Respond Differently to Ultraviolet Radiation: Implications for Retinal Diseases

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Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam; Cáceres-del-Carpio, Javier; Tarek, Mohamed; Chwa, Marilyn; Atilano, Shari R.; Ramirez, Claudio; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin; Kenney, M. Cristina

2014-01-01

Background It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. Methodology/Principal Findings Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. Conclusion/Significance In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be

[Identification of the Mycobacterium tuberculosis Beijing lineage in Ecuador].

Science.gov (United States)

Jiménez, Patricia; Calvopiña, Karina; Herrera, Diana; Rojas, Carlos; Pérez-Lago, Laura; Grijalva, Marcelo; Guna, Remedios; García-de Viedma, Darío

2017-06-01

Mycobacterium tuberculosis Beijing lineage isolates are considered to be especially virulent, transmissible and prone to acquire resistances. Beijing strains have been reported worldwide, but studies in Latin America are still scarce. The only multinational study performed in the region indicated a heterogeneous distribution for this lineage, which was absent in Chile, Colombia and Ecuador, although further studies found the lineage in Chile and Colombia. To search for the presence of the Beijing lineage in Ecuador, the only country in the region where it remains unreported. We obtained a convenience sample (2006-2012) from two hospitals covering different populations. The isolates were genotyped using 24-MIRU-VNTR. Lineages were assigned by comparing their patterns to those in the MIRU-VNTRplus platform. Isolates belonging to the Beijing lineage were confirmed by allele-specific PCR. We identified the first Beijing isolate in Ecuador in an unexpected epidemiological scenario: A patient was infected in the Andean region, in a population with low mobility and far from the borders of the neighboring countries where Beijing strains had been previously reported. This is the first report of the presence of the Beijing lineage in Ecuador in an unusual epidemiological context that deserves special attention.

Circulation of influenza B lineages in northern Viet Nam, 2007-2014.

Science.gov (United States)

Le, Thi Thanh; Pham, Thu Hang; Pham, Thi Hien; Nguyen, Le Khanh Hang; Nguyen, Co Thach; Hoang, Vu Mai Phuong; Tran, Thu Huong; Nguyen, Vu Son; Ngo, Huong Giang; Le, Quynh Mai

2015-01-01

Influenza B viruses circulate throughout Viet Nam, and their activities vary by region. There have been two antigenically distinct lineages of influenza B viruses co-circulating in the past 20 years; however, only one lineage is selected as a component of contemporary trivalent seasonal influenza vaccines. To improve the understanding of circulating influenza B lineages and influenza vaccine mismatches, we report the virus lineages circulating in northern Viet Nam over an eight-year period (2007-2014). Lineages of 331 influenza B viruses were characterized by haemagglutination inhibition assay against standard reference ferret (Yamagata) and sheep (Victoria) antisera. Sequence analysis of the haemagglutinin gene was performed in 64 selected influenza B isolates. The proportion of influenza B lineages changed by year. The Yamagata lineage predominated in 2007, 2008 and 2012; the Victoria lineage predominated in 2009-2014 except 2012. The two lineages showed continuous evolution over time. The Northern Hemisphere's influenza vaccine components were mismatched with the predominant circulating viruses in 2007, 2009 and 2014. The seasonality of influenza B activity is more variable in tropical and subtropical regions than in temperate zones. Our data showed a common co-circulation of both influenza B lineages in northern Viet Nam, and it was difficult to predict which one was the predominant lineage. Quadrivalent influenza vaccines containing both lineages may improve the effectiveness of influenza vaccine programmes in the future.

MtDNA barcode identification of fish larvae in the southern Great Barrier Reef – Australia

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Graham G. Pegg

2006-10-01

Full Text Available Planktonic larvae were captured above a shallow coral reef study site on the Great Barrier Reef (GBR around spring-summer new moon periods (October-February using light trap or net capture devices. Larvae were identified to the genus or species level by comparison with a phylogenetic tree of tropical marine fish species using mtDNA HVR1 sequence data. Further analysis showed that within-species HVR1 sequence variation was typically 1-3%, whereas between-species variation for the same genus ranged up to 50%, supporting the suitability of HVR1 for species identification. Given the current worldwide interest in DNA barcoding and species identification using an alternative mtDNA gene marker (cox1, we also explored the efficacy of different primer sets for amplification of cox1 in reef fish, and its suitability for species identification. Of those tested, the Fish-F1 and -R1 primer set recently reported by Ward et al. (2005 gave the best results.

Dynamic formation of asexual diploid and polyploid lineages: multilocus analysis of Cobitis reveals the mechanisms maintaining the diversity of clones.

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Karel Janko

Full Text Available Given the hybrid genomic constitutions and increased ploidy of many asexual animals, the identification of processes governing the origin and maintenance of clonal diversity provides useful information about the evolutionary consequences of interspecific hybridization, asexuality and polyploidy. In order to understand the processes driving observed diversity of biotypes and clones in the Cobitis taenia hybrid complex, we performed fine-scale genetic analysis of Central European hybrid zone between two sexual species using microsatellite genotyping and mtDNA sequencing. We found that the hybrid zone is populated by an assemblage of clonally (gynogenetically reproducing di-, tri- and tetraploid hybrid lineages and that successful clones, which are able of spatial expansion, recruit from two ploidy levels, i.e. diploid and triploid. We further compared the distribution of observed estimates of clonal ages to theoretical distributions simulated under various assumptions and showed that new clones are most likely continuously recruited from ancestral populations. This suggests that the clonal diversity is maintained by dynamic equilibrium between origination and extinction of clonal lineages. On the other hand, an interclonal selection is implied by nonrandom spatial distribution of individual clones with respect to the coexisting sexual species. Importantly, there was no evidence for sexually reproducing hybrids or clonally reproducing non-hybrid forms. Together with previous successful laboratory synthesis of clonal Cobitis hybrids, our data thus provide the most compelling evidence that 1 the origin of asexuality is causally linked to interspecific hybridization; 2 successful establishment of clones is not restricted to one specific ploidy level and 3 the initiation of clonality and polyploidy may be dynamic and continuous in asexual complexes.

Cell lineage branching as a strategy for proliferative control.

Science.gov (United States)

Buzi, Gentian; Lander, Arthur D; Khammash, Mustafa

2015-02-19

How tissue and organ sizes are specified is one of the great unsolved mysteries in biology. Experiments and mathematical modeling implicate feedback control of cell lineage progression, but a broad understanding of what lineage feedback accomplishes is lacking. By exploring the possible effects of various biologically relevant disturbances on the dynamic and steady state behaviors of stem cell lineages, we find that the simplest and most frequently studied form of lineage feedback - which we term renewal control - suffers from several serious drawbacks. These reflect fundamental performance limits dictated by universal conservation-type laws, and are independent of parameter choice. Here we show that introducing lineage branches can circumvent all such limitations, permitting effective attenuation of a wide range of perturbations. The type of feedback that achieves such performance - which we term fate control - involves promotion of lineage branching at the expense of both renewal and (primary) differentiation. We discuss the evidence that feedback of just this type occurs in vivo, and plays a role in tissue growth control. Regulated lineage branching is an effective strategy for dealing with disturbances in stem cell systems. The existence of this strategy provides a dynamics-based justification for feedback control of cell fate in vivo.

Data on haplotype diversity in the hypervariable region I, II and III of mtDNA amongst the Brahmin population of Haryana

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Kapil Verma

2018-04-01

Full Text Available Human mitochondrial DNA (mtDNA is routinely analysed for pathogenic mutations, evolutionary studies, estimation of time of divergence within or between species, phylogenetic studies and identification of degraded remains. The data on various regions of human mtDNA has added enormously to the knowledge pool of population genetics as well as forensic genetics. The displacement-loop (D-loop in the control region of mtDNA is rated as the most rapidly evolving part, due to the presence of variations in this region. The control region consists of three hypervariable regions. These hypervariable regions (HVI, HVII and HVIII tend to mutate 5–10 times faster than nuclear DNA. The high mutation rate of these hypervariable regions is used in population genetic studies and human identity testing. In the present data, potentially informative hypervariable regions of mitochondrial DNA (mtDNA i.e. HVI (np 16024–16365, HVII (np 73–340 and HVIII (np 438–576 were estimated to understand the genetic diversity amongst Brahmin population of Haryana. Blood samples had been collected from maternally unrelated individuals from the different districts of Haryana. An array of parameters comprising of polymorphic sites, transitions, transversions, deletions, gene diversity, nucleotide diversity, pairwise differences, Tajima's D test, Fu's Fs test, mismatch observed variance and expected heterozygosity were estimated. The observed polymorphisms with their respective haplogroups in comparison to rCRS were assigned. Keywords: Mitochondrial DNA, D-loop, Hypervariable regions, Forensic genetics

Biome specificity of distinct genetic lineages within the four-striped mouse Rhabdomys pumilio (Rodentia: Muridae) from southern Africa with implications for taxonomy.

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du Toit, Nina; van Vuuren, Bettine Jansen; Matthee, Sonja; Matthee, Conrad A

2012-10-01

Within southern Africa, a link between past climatic changes and faunal diversification has been hypothesized for a diversity of taxa. To test the hypothesis that evolutionary divergences may be correlated to vegetation changes (induced by changes in climate), we selected the widely distributed four-striped mouse, Rhabdomys, as a model. Two species are currently recognized, the mesic-adapted R. dilectus and arid-adapted R. pumilio. However, the morphology-based taxonomy and the distribution boundaries of previously described subspecies remain poorly defined. The current study, which spans seven biomes, focuses on the spatial genetic structure of the arid-adapted R. pumilio (521 specimens from 31 localities), but also includes limited sampling of the mesic-adapted R. dilectus (33 specimens from 10 localities) to act as a reference for interspecific variation within the genus. The mitochondrial COI gene and four nuclear introns (Eef1a1, MGF, SPTBN1, Bfib7) were used for the construction of gene trees. Mitochondrial DNA analyses indicate that Rhabdomys consists of four reciprocally monophyletic, geographically structured clades, with three distinct lineages present within the arid-adapted R. pumilio. These monophyletic lineages differ by at least 7.9% (±0.3) and these results are partly confirmed by a multilocus network of the combined nuclear intron dataset. Ecological niche modeling in MaxEnt supports a strong correlation between regional biomes and the distribution of distinct evolutionary lineages of Rhabdomys. A Bayesian relaxed molecular clock suggests that the geographic clades diverged between 3.09 and 4.30Ma, supporting the hypothesis that the radiation within the genus coincides with paleoclimatic changes (and the establishment of the biomes) characterizing the Miocene-Pliocene boundary. Marked genetic divergence at the mitochondrial DNA level, coupled with strong nuclear and mtDNA signals of non-monophyly of R. pumilio, support the notion that a taxonomic

Reconstructing the complex evolutionary history of mobile plasmids in red algal genomes

Science.gov (United States)

Lee, JunMo; Kim, Kyeong Mi; Yang, Eun Chan; Miller, Kathy Ann; Boo, Sung Min; Bhattacharya, Debashish; Yoon, Hwan Su

2016-01-01

The integration of foreign DNA into algal and plant plastid genomes is a rare event, with only a few known examples of horizontal gene transfer (HGT). Plasmids, which are well-studied drivers of HGT in prokaryotes, have been reported previously in red algae (Rhodophyta). However, the distribution of these mobile DNA elements and their sites of integration into the plastid (ptDNA), mitochondrial (mtDNA), and nuclear genomes of Rhodophyta remain unknown. Here we reconstructed the complex evolutionary history of plasmid-derived DNAs in red algae. Comparative analysis of 21 rhodophyte ptDNAs, including new genome data for 5 species, turned up 22 plasmid-derived open reading frames (ORFs) that showed syntenic and copy number variation among species, but were conserved within different individuals in three lineages. Several plasmid-derived homologs were found not only in ptDNA but also in mtDNA and in the nuclear genome of green plants, stramenopiles, and rhizarians. Phylogenetic and plasmid-derived ORF analyses showed that the majority of plasmid DNAs originated within red algae, whereas others were derived from cyanobacteria, other bacteria, and viruses. Our results elucidate the evolution of plasmid DNAs in red algae and suggest that they spread as parasitic genetic elements. This hypothesis is consistent with their sporadic distribution within Rhodophyta. PMID:27030297

Mitochondrial DNA analysis suggests a Chibchan migration into Colombia

OpenAIRE

Noguera-Santamaría, Maria Claudia; Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana. Grupo de Genética Humana, Facultad de Medicina, Universidad de La Sabana. Facultad de Ciencias de la Salud. Grupo Gisafaco. Corporación Universitaria Remington; Anderson, Carl Edlund; Department of Foreign Languages & Cultures, Universidad de La Sabana; Uricoechea, Daniel; Grupo de Genética Humana, Facultad de Medicina, Universidad de La Sabana; Durán, Clemencia; Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana.; Briceño-Balcázar, Ignacio; Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana Grupo de Genética Humana, Facultad de Medicina, Universidad de La Sabana; Bernal-Villegas, Jaime; Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana Universidad Tecnológica de Bolívar

2015-01-01

The characterization of mitochondrial DNA (mtDNA) allows the establishment of genetic structures and phylogenetic relationships in human populations, tracing lineages far back in time. We analysed samples of mtDNA from twenty (20) Native American populations (700 individuals) dispersed throughout Colombian territory. Samples were collected during 1989-1993 in the context of the program Expedición Humana (“Human Expedition”) and stored in the Biological Repository of the Institute of Human Gen...

Mosaic maternal ancestry in the Great Lakes region of East Africa.

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Gomes, Verónica; Pala, Maria; Salas, Antonio; Álvarez-Iglesias, Vanesa; Amorim, António; Gómez-Carballa, Alberto; Carracedo, Ángel; Clarke, Douglas J; Hill, Catherine; Mormina, Maru; Shaw, Marie-Anne; Dunne, David W; Pereira, Rui; Pereira, Vânia; Prata, Maria João; Sánchez-Diz, Paula; Rito, Teresa; Soares, Pedro; Gusmão, Leonor; Richards, Martin B

2015-09-01

The Great Lakes lie within a region of East Africa with very high human genetic diversity, home of many ethno-linguistic groups usually assumed to be the product of a small number of major dispersals. However, our knowledge of these dispersals relies primarily on the inferences of historical, linguistics and oral traditions, with attempts to match up the archaeological evidence where possible. This is an obvious area to which archaeogenetics can contribute, yet Uganda, at the heart of these developments, has not been studied for mitochondrial DNA (mtDNA) variation. Here, we compare mtDNA lineages at this putative genetic crossroads across 409 representatives of the major language groups: Bantu speakers and Eastern and Western Nilotic speakers. We show that Uganda harbours one of the highest mtDNA diversities within and between linguistic groups, with the various groups significantly differentiated from each other. Despite an inferred linguistic origin in South Sudan, the data from the two Nilotic-speaking groups point to a much more complex history, involving not only possible dispersals from Sudan and the Horn but also large-scale assimilation of autochthonous lineages within East Africa and even Uganda itself. The Eastern Nilotic group also carries signals characteristic of West-Central Africa, primarily due to Bantu influence, whereas a much stronger signal in the Western Nilotic group suggests direct West-Central African ancestry. Bantu speakers share lineages with both Nilotic groups, and also harbour East African lineages not found in Western Nilotic speakers, likely due to assimilating indigenous populations since arriving in the region ~3000 years ago.

Human maternal heritage in Andalusia (Spain): its composition reveals high internal complexity and distinctive influences of mtDNA haplogroups U6 and L in the western and eastern side of region.

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Hernández, Candela L; Reales, Guillermo; Dugoujon, Jean-Michel; Novelletto, Andrea; Rodríguez, Juan Nicolás; Cuesta, Pedro; Calderón, Rosario

2014-01-24

The archeology and history of the ancient Mediterranean have shown that this sea has been a permeable obstacle to human migration. Multiple cultural exchanges around the Mediterranean have taken place with presumably population admixtures. A gravitational territory of those migrations has been the Iberian Peninsula. Here we present a comprehensive analysis of the maternal gene pool, by means of control region sequencing and PCR-RFLP typing, of autochthonous Andalusians originating from the coastal provinces of Huelva and Granada, located respectively in the west and the east of the region. The mtDNA haplogroup composition of these two southern Spanish populations has revealed a wide spectrum of haplogroups from different geographical origins. The registered frequencies of Eurasian markers, together with the high incidence and diversification of African maternal lineages (15% of the total mitochondrial variability) among Huelva Andalusians when compared to its eastwards relatives of Granada and other Iberian populations, constitute relevant findings unknown up-to-date on the characteristics of mtDNA within Andalusia that testifies a female population substructure. Therefore, Andalusia must not be considered a single, unique population. The maternal legacy among Andalusians reflects distinctive local histories, pointing out the role of the westernmost territory of Peninsular Spain as a noticeable recipient of multiple and diverse human migrations. The obtained results underline the necessity of further research on genetic relationships in both sides of the western Mediterranean, using carefully collected samples from autochthonous individuals. Many studies have focused on recent North African gene flow towards Iberia, yet scientific attention should be now directed to thoroughly study the introduction of European genes in northwest Africa across the sea, in order to determine its magnitude, timescale and methods, and to compare them to those terrestrial movements

Rare mtDNA haplogroups and genetic differences in rich and poor Danish Iron-Age villages

DEFF Research Database (Denmark)

Melchior, L; Gilbert, M T P; Kivisild, T

2008-01-01

The Roman Iron-Age (0-400 AD) in Southern Scandinavia was a formative period, where the society changed from archaic chiefdoms to a true state formation, and the population composition has likely changed in this period due to immigrants from Middle Scandinavia. We have analyzed mtDNA from 22 indi...

Mitochondrial and Y-chromosomal profile of the Kazakh population from East Kazakhstan

Science.gov (United States)

Tarlykov, Pavel V.; Zholdybayeva, Elena V.; Akilzhanova, Ainur R.; Nurkina, Zhannur M.; Sabitov, Zhaxylyk M.; Rakhypbekov, Tolebay K.; Ramanculov, Erlan M.

2013-01-01

Aim To study the genetic relationship of Kazakhs from East Kazakhstan to other Eurasian populations by examining paternal and maternal DNA lineages. Methods Whole blood samples were collected in 2010 from 160 unrelated healthy Kazakhs residing in East Kazakhstan. Genomic DNA was extracted with Wizard® genomic DNA Purification Kit. Nucleotide sequence of hypervariable segment I of mitochondrial DNA (mtDNA) was determined and analyzed. Seventeen Y-short tandem repeat (STR) loci were studied in 67 samples with the AmpFiSTR Y-filer PCR Amplification Kit. In addition, mtDNA data for 2701 individuals and Y-STR data for 677 individuals were retrieved from the literature for comparison. Results There was a high degree of genetic differentiation on the level of mitochondrial DNA. The majority of maternal lineages belonged to haplogroups common in Central Asia. In contrast, Y-STR data showed very low genetic diversity, with the relative frequency of the predominant haplotype of 0.612. Conclusion The results revealed different migration patterns in the population sample, showing there had been more migration among women. mtDNA genetic diversity in this population was equivalent to that in other Central Asian populations. Genetic evidence suggests the existence of a single paternal founder lineage in the population of East Kazakhstan, which is consistent with verbal genealogical data of the local tribes. PMID:23444242

Introgression and selection shaped the evolutionary history of sympatric sister-species of coral reef fishes (genus: Haemulon)

KAUST Repository

Bernal, Moisés A.

2016-11-22

Closely related marine species with large overlapping ranges provide opportunities to study mechanisms of speciation, particularly when there is evidence of gene flow between such lineages. Here, we focus on a case of hybridization between the sympatric sister-species Haemulon maculicauda and H. flaviguttatum, using Sanger sequencing of mitochondrial and nuclear loci, as well as 2422 single nucleotide polymorphisms (SNPs) obtained via restriction site-associated DNA sequencing (RADSeq). Mitochondrial markers revealed a shared haplotype for COI and low divergence for CytB and CR between the sister-species. On the other hand, complete lineage sorting was observed at the nuclear loci and most of the SNPs. Under neutral expectations, the smaller effective population size of mtDNA should lead to fixation of mutations faster than nDNA. Thus, these results suggest that hybridization in the recent past (0.174-0.263Ma) led to introgression of the mtDNA, with little effect on the nuclear genome. Analyses of the SNP data revealed 28 loci potentially under divergent selection between the two species. The combination of mtDNA introgression and limited nuclear DNA introgression provides a mechanism for the evolution of independent lineages despite recurrent hybridization events. This study adds to the growing body of research that exemplifies how genetic divergence can be maintained in the presence of gene flow between closely related species.

Introgression and selection shaped the evolutionary history of sympatric sister-species of coral reef fishes (genus: Haemulon)

KAUST Repository

Bernal, Moisé s A.; Gaither, Michelle R.; Simison, W. Brian; Rocha, Luiz A.

2016-01-01

Closely related marine species with large overlapping ranges provide opportunities to study mechanisms of speciation, particularly when there is evidence of gene flow between such lineages. Here, we focus on a case of hybridization between the sympatric sister-species Haemulon maculicauda and H. flaviguttatum, using Sanger sequencing of mitochondrial and nuclear loci, as well as 2422 single nucleotide polymorphisms (SNPs) obtained via restriction site-associated DNA sequencing (RADSeq). Mitochondrial markers revealed a shared haplotype for COI and low divergence for CytB and CR between the sister-species. On the other hand, complete lineage sorting was observed at the nuclear loci and most of the SNPs. Under neutral expectations, the smaller effective population size of mtDNA should lead to fixation of mutations faster than nDNA. Thus, these results suggest that hybridization in the recent past (0.174-0.263Ma) led to introgression of the mtDNA, with little effect on the nuclear genome. Analyses of the SNP data revealed 28 loci potentially under divergent selection between the two species. The combination of mtDNA introgression and limited nuclear DNA introgression provides a mechanism for the evolution of independent lineages despite recurrent hybridization events. This study adds to the growing body of research that exemplifies how genetic divergence can be maintained in the presence of gene flow between closely related species.

The phylogeny of the four pan-American MtDNA haplogroups: implications for evolutionary and disease studies.

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Alessandro Achilli

Full Text Available Only a limited number of complete mitochondrial genome sequences belonging to Native American haplogroups were available until recently, which left America as the continent with the least amount of information about sequence variation of entire mitochondrial DNAs. In this study, a comprehensive overview of all available complete mitochondrial DNA (mtDNA genomes of the four pan-American haplogroups A2, B2, C1, and D1 is provided by revising the information scattered throughout GenBank and the literature, and adding 14 novel mtDNA sequences. The phylogenies of haplogroups A2, B2, C1, and D1 reveal a large number of sub-haplogroups but suggest that the ancestral Beringian population(s contributed only six (successful founder haplotypes to these haplogroups. The derived clades are overall starlike with coalescence times ranging from 18,000 to 21,000 years (with one exception using the conventional calibration. The average of about 19,000 years somewhat contrasts with the corresponding lower age of about 13,500 years that was recently proposed by employing a different calibration and estimation approach. Our estimate indicates a human entry and spread of the pan-American haplogroups into the Americas right after the peak of the Last Glacial Maximum and comfortably agrees with the undisputed ages of the earliest Paleoindians in South America. In addition, the phylogenetic approach also indicates that the pathogenic status proposed for various mtDNA mutations, which actually define branches of Native American haplogroups, was based on insufficient grounds.

Mitochondrial and Y chromosome haplotype motifs as diagnostic markers of Jewish ancestry: a reconsideration.

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Sergio eTofanelli

2014-11-01

Full Text Available Several authors have proposed haplotype motifs based on site variants at the mitochondrial genome (mtDNA and the non-recombining portion of the Y chromosome (NRY to trace the genealogies of Jewish people. Here, we analyzed their main approaches and test the feasibility of adopting motifs as ancestry markers through construction of a large database of mtDNA and NRY haplotypes from public genetic genealogical repositories. We verified the reliability of Jewish ancestry prediction based on the Cohen and Levite Modal Haplotypes in their classical 6 STR marker format or in the extended 12 STR format, as well as four founder mtDNA lineages (HVS-I segments accounting for about 40% of the current population of Ashkenazi Jews. For this purpose we compared haplotype composition in individuals of self-reported Jewish ancestry with the rest of European, African or Middle Eastern samples, to test for non-random association of ethno-geographic groups and haplotypes. Overall, NRY and mtDNA based motifs, previously reported to differentiate between groups, were found to be more represented in Jewish compared to non-Jewish groups. However, this seems to stem from common ancestors of Jewish lineages being rather recent respect to ancestors of non-Jewish lineages with the same haplotype signatures. Moreover, the polyphyly of haplotypes which contain the proposed motifs and the misuse of constant mutation rates heavily affected previous attempts to correctly dating the origin of common ancestries. Accordingly, our results stress the limitations of using the above haplotype motifs as reliable Jewish ancestry predictors and show its inadequacy for forensic or genealogical purposes.

Molecular genetic differentiation in earthworms inhabiting a heterogeneous Pb-polluted landscape

Energy Technology Data Exchange (ETDEWEB)

Andre, J., E-mail: Andrej@cardiff.ac.u [Cardiff School of Biosciences, Cardiff University, BIOSI 1, Museum Avenue, Cardiff CF10 3TL (United Kingdom); Department of Soil Science, School of Human and Environmental Sciences, University of Reading, Whiteknights, Reading RG6 6DW (United Kingdom); King, R.A. [Cardiff School of Biosciences, Cardiff University, BIOSI 1, Museum Avenue, Cardiff CF10 3TL (United Kingdom); Stuerzenbaum, S.R. [King' s College London, School of Biomedical and Health Sciences, Pharmaceutical Sciences Division, London SE1 9NH (United Kingdom); Kille, P. [Cardiff School of Biosciences, Cardiff University, BIOSI 1, Museum Avenue, Cardiff CF10 3TL (United Kingdom); Hodson, M.E. [Department of Soil Science, School of Human and Environmental Sciences, University of Reading, Whiteknights, Reading RG6 6DW (United Kingdom); Morgan, A.J. [Cardiff School of Biosciences, Cardiff University, BIOSI 1, Museum Avenue, Cardiff CF10 3TL (United Kingdom)

2010-03-15

A Pb-mine site situated on acidic soil, but comprising of Ca-enriched islands around derelict buildings was used to study the spatial pattern of genetic diversity in Lumbricus rubellus. Two distinct genetic lineages ('A' and 'B'), differentiated at both the mitochondrial (mtDNA COII) and nuclear level (AFLPs) were revealed with a mean inter-lineage mtDNA sequence divergence of approximately 13%, indicative of a cryptic species complex. AFLP analysis indicates that lineage A individuals within one central 'ecological island' site are uniquely clustered, with little genetic overlap with lineage A individuals at the two peripheral sites. FTIR microspectroscopy of Pb-sequestering chloragocytes revealed different phosphate profiles in residents of adjacent acidic and calcareous islands. Bioinformatics found over-representation of Ca pathway genes in EST{sub Pb} libraries. Subsequent sequencing of a Ca-transport gene, SERCA, revealed mutations in the protein's cytosolic domain. We recommend the mandatory genotyping of all individuals prior to field-based ecotoxicological assays, particularly those using discriminating genomic technologies. - Landscapes punctuated by Pb-polluted islands have engendered local genetic differentiation in resident earthworms.

mtDNA as a Mediator for Expression of Hypoxia-Inducible Factor 1α and ROS in Hypoxic Neuroblastoma Cells.

Science.gov (United States)

Kuo, Chung-Wen; Tsai, Meng-Han; Lin, Tsu-Kung; Tiao, Mao-Meng; Wang, Pei-Wen; Chuang, Jiin-Haur; Chen, Shang-Der; Liou, Chia-Wei

2017-06-07

Mitochondria consume O₂ to produce ATP and are critical for adaption of hypoxia, but the role of mitochondria in HIF-1α pathway is as yet unclear. In this study, mitochondrial DNA (mtDNA) enriched (SK-N-AS) and depleted (ρ⁰) cells of neuroblastoma were cultured in a hypoxic chamber to simulate a hypoxic condition and then the major components involved in mitochondrial related pathways, hypoxia-inducible factor 1α (HIF-1α) and reactive oxygen species (ROS) were measured. The results showed that hypoxia-stimulated exposure elevated expression of HIF-1α, which was additionally influenced by level of generated ROS within the cytosol. Moreover, elevation of HIF-1α also resulted in increases of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase kinase 1 (PDK1) in both hypoxic cells. The expression of mitochondrial biogenesis related proteins and metabolic components were noted to increase significantly in hypoxic SK-N-AS cells, indicating that mtDNA was involved in mitochondrial retrograde signaling and metabolic pathways. An analysis of dynamic proteins found elevated levels of HIF-1α causing an increased expression of dynamin-related protein 1 (DRP1) during hypoxia; further, the existence of mtDNA also resulted in higher expression of DRP1 during hypoxia. By using siRNA of HIF-1α or DRP1, expression of DRP1 decreased after suppression of HIF-1α; moreover, the expression of HIF-1α was also affected by the suppression of DRP1. In this study, we demonstrated that mtDNA is a mediator of HIF-1α in eliciting metabolic reprogramming, and mitochondrial biogenesis. Identification of a mutual relationship between HIF-1α and DRP1 may be a critical tool in the future development of clinical applications.

Novel 12S mtDNA findings in sloths (Pilosa, Folivora) and anteaters (Pilosa, Vermilingua) suggest a true case of long branch attraction

OpenAIRE

Barros, Maria Claudene; Sampaio, Iracilda; Schneider, Horacio

2008-01-01

We sequenced 12S RNA mtDNA for the majority of the extant species of sloths and anteaters and compared our results with previous data obtained by our group using 16S RNA mtDNA in the same specimens and to GenBank sequences of the extinct giant sloth Mylodon. Our results suggest that pigmy-anteaters may be a case of the long-branch attraction phenomenon and also show the large genetic difference between the Amazonian and Atlantic forest three-toed sloths, contrasting with the small differences...

Diversity rankings among bacterial lineages in soil.

Science.gov (United States)

Youssef, Noha H; Elshahed, Mostafa S

2009-03-01

We used rarefaction curve analysis and diversity ordering-based approaches to rank the 11 most frequently encountered bacterial lineages in soil according to diversity in 5 previously reported 16S rRNA gene clone libraries derived from agricultural, undisturbed tall grass prairie and forest soils (n=26,140, 28 328, 31 818, 13 001 and 53 533). The Planctomycetes, Firmicutes and the delta-Proteobacteria were consistently ranked among the most diverse lineages in all data sets, whereas the Verrucomicrobia, Gemmatimonadetes and beta-Proteobacteria were consistently ranked among the least diverse. On the other hand, the rankings of alpha-Proteobacteria, Acidobacteria, Actinobacteria, Bacteroidetes and Chloroflexi varied widely in different soil clone libraries. In general, lineages exhibiting largest differences in diversity rankings also exhibited the largest difference in relative abundance in the data sets examined. Within these lineages, a positive correlation between relative abundance and diversity was observed within the Acidobacteria, Actinobacteria and Chloroflexi, and a negative diversity-abundance correlation was observed within the Bacteroidetes. The ecological and evolutionary implications of these results are discussed.

Environmental filtering of eudicot lineages underlies phylogenetic clustering in tropical South American flooded forests.

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Aldana, Ana M; Carlucci, Marcos B; Fine, Paul V A; Stevenson, Pablo R

2017-02-01

The phylogenetic community assembly approach has been used to elucidate the role of ecological and historical processes in shaping tropical tree communities. Recent studies have shown that stressful environments, such as seasonally dry, white-sand and flooded forests tend to be phylogenetically clustered, arguing for niche conservatism as the main driver for this pattern. Very few studies have attempted to identify the lineages that contribute to such assembly patterns. We aimed to improve our understanding of the assembly of flooded forest tree communities in Northern South America by asking the following questions: are seasonally flooded forests phylogenetically clustered? If so, which angiosperm lineages are over-represented in seasonally flooded forests? To assess our hypotheses, we investigated seasonally flooded and terra firme forests from the Magdalena, Orinoco and Amazon Basins, in Colombia. Our results show that, regardless of the river basin in which they are located, seasonally flooded forests of Northern South America tend to be phylogenetically clustered, which means that the more abundant taxa in these forests are more closely related to each other than expected by chance. Based on our alpha and beta phylodiversity analyses we interpret that eudicots are more likely to adapt to extreme environments such as seasonally flooded forests, which indicates the importance of environmental filtering in the assembly of the Neotropical flora.

Experimental infection of rock pigeons (Columba livia) with three West Nile virus lineage 1 strains isolated in Italy between 2009 and 2012.

Science.gov (United States)

Spedicato, M; Carmine, I; Bellacicco, A L; Marruchella, G; Marini, V; Pisciella, M; Di Francesco, G; Lorusso, A; Monaco, F; Savini, G

2016-04-01

West Nile virus (WNV) circulation dynamics in the context of the urban environment is not yet elucidated. In this perspective, three groups of eight rock pigeons (Columbia livia) were inoculated with three WNV lineage 1 strains isolated in Italy between 2009 and 2012. The pigeons did not develop any clinical signs consistent with WNV acute infection. All animals seroconverted and shed virus up to 15 days post-infection by the oral or cloacal routes. In all infected groups viraemia lasted for 4 days post-infection. No WNV-specific gross or histological lesions were found in infected birds compared to control birds and immunohistochemistry remained constantly negative from all tissues. The reservoir competence index was also assessed and it ranged between 0·11 and 0·14. This study demonstrates that pigeons are competent reservoir hosts for Italian WNV lineage 1 circulating strains thus potentially posing a risk to the public health system.

Cell lineage analysis of the mammalian female germline.

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Yitzhak Reizel

Full Text Available Fundamental aspects of embryonic and post-natal development, including maintenance of the mammalian female germline, are largely unknown. Here we employ a retrospective, phylogenetic-based method for reconstructing cell lineage trees utilizing somatic mutations accumulated in microsatellites, to study female germline dynamics in mice. Reconstructed cell lineage trees can be used to estimate lineage relationships between different cell types, as well as cell depth (number of cell divisions since the zygote. We show that, in the reconstructed mouse cell lineage trees, oocytes form clusters that are separate from hematopoietic and mesenchymal stem cells, both in young and old mice, indicating that these populations belong to distinct lineages. Furthermore, while cumulus cells sampled from different ovarian follicles are distinctly clustered on the reconstructed trees, oocytes from the left and right ovaries are not, suggesting a mixing of their progenitor pools. We also observed an increase in oocyte depth with mouse age, which can be explained either by depth-guided selection of oocytes for ovulation or by post-natal renewal. Overall, our study sheds light on substantial novel aspects of female germline preservation and development.

Sex-specific influences of mtDNA mitotype and diet on mitochondrial functions and physiological traits in Drosophila melanogaster.

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Wen C Aw

Full Text Available Here we determine the sex-specific influence of mtDNA type (mitotype and diet on mitochondrial functions and physiology in two Drosophila melanogaster lines. In many species, males and females differ in aspects of their energy production. These sex-specific influences may be caused by differences in evolutionary history and physiological functions. We predicted the influence of mtDNA mutations should be stronger in males than females as a result of the organelle's maternal mode of inheritance in the majority of metazoans. In contrast, we predicted the influence of diet would be greater in females due to higher metabolic flexibility. We included four diets that differed in their protein: carbohydrate (P:C ratios as they are the two-major energy-yielding macronutrients in the fly diet. We assayed four mitochondrial function traits (Complex I oxidative phosphorylation, reactive oxygen species production, superoxide dismutase activity, and mtDNA copy number and four physiological traits (fecundity, longevity, lipid content, and starvation resistance. Traits were assayed at 11 d and 25 d of age. Consistent with predictions we observe that the mitotype influenced males more than females supporting the hypothesis of a sex-specific selective sieve in the mitochondrial genome caused by the maternal inheritance of mitochondria. Also, consistent with predictions, we found that the diet influenced females more than males.

[Differences on geographic distribution of rabies virus lineages in China].

Science.gov (United States)

Wang, Q; Li, M L; Chen, Y; Wang, B; Tao, X Y; Zhu, W Y

2018-04-10

Objective: To study the lineages of rabies virus and the epidemic characteristics in different provincial populations of China, to provide information for the development of control and prevention measures in each respective provinces. Methods: Full length N and G genes and full-genome of epidemic strains of rabies virus collected in China were downloaded from GenBank and combined with newly sequenced strains by our lab. Each strain was classified under six lineages of China rabies by constructing phylogenetic trees based on the N or G sequences. Numbers of strains and lineages in each province were counted and compared. Results: Six lineages (China Ⅰ-Ⅵ) were prevalent in China, with 4 found in Yunnan and Hunan. In 6 provinces, including Henan and Fujian, 3 lineages were found. In 8 provinces, including Shanghai and Jiangxi, 2 lineages were found Only 1 lineage, were found in Beijing, Tianjin and other 12 provinces. the China Ⅰ, was the dominant one in 25 provinces. In recent years, China Ⅲ had been found in wild animals and spread over livestock in Inner Mongolia and Xinjiang areas. Qinghai and Tibet had been influenced by China Ⅳ, which also been found in wild animals of Inner Mongolia and Heilongjiang. Conclusion: There had been obvious differences in lineages and strain numbers of rabies virus identified in different provinces in China.

Three brown trout Salmo trutta lineages in Corsica described through allozyme variation.

Science.gov (United States)

Berrebi, P

2015-01-01

The brown trout Salmo trutta is represented by three lineages in Corsica: (1) an ancestral Corsican lineage, (2) a Mediterranean lineage and (3) a recently stocked domestic Atlantic S. trutta lineage (all are interfertile); the main focus of this study was the ancestral Corsican S. trutta, but the other lineages were also considered. A total of 38 samples captured between 1993 and 1998 were analysed, with nearly 1000 individuals considered overall. The Corsican ancestral lineage (Adriatic lineage according to the mitochondrial DNA control region nomenclature, AD) mostly inhabits streams in the southern half of the island; the Mediterranean lineage (ME) is present more in the north, especially in Golu River, but most populations are an admixture of these lineages and the domestic Atlantic S. trutta (AT). Locations where the Corsican ancestral S. trutta is dominant are now protected against stocking and sometimes fishing is also forbidden. The presence of the Corsican S. trutta is unique in France. © 2014 The Fisheries Society of the British Isles.

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque’s and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines

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Jonathan O. Rayner

2018-05-01

Full Text Available The establishment of a well characterized non-human primate model of Zika virus (ZIKV infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains, obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasure development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge.

Comparative Pathogenesis of Asian and African-Lineage Zika Virus in Indian Rhesus Macaque’s and Development of a Non-Human Primate Model Suitable for the Evaluation of New Drugs and Vaccines

Science.gov (United States)

Kalkeri, Raj; Goebel, Scott; Cai, Zhaohui; Green, Brian; Lin, Shuling; Snyder, Beth; Hagelin, Kimberly; Walters, Kevin B.; Koide, Fusataka

2018-01-01

The establishment of a well characterized non-human primate model of Zika virus (ZIKV) infection is critical for the development of medical interventions. In this study, challenging Indian rhesus macaques (IRMs) with ZIKV strains of the Asian lineage resulted in dose-dependent peak viral loads between days 2 and 5 post infection and a robust immune response which protected the animals from homologous and heterologous re-challenge. In contrast, viremia in IRMs challenged with an African lineage strain was below the assay’s lower limit of quantitation, and the immune response was insufficient to protect from re-challenge. These results corroborate previous observations but are contrary to reports using other African strains, obviating the need for additional studies to elucidate the variables contributing to the disparities. Nonetheless, the utility of an Asian lineage ZIKV IRM model for countermeasure development was verified by vaccinating animals with a formalin inactivated reference vaccine and demonstrating sterilizing immunity against a subsequent subcutaneous challenge. PMID:29723973

Phylogenetic patterns in populations of Chilean species of the genus Orestias (Teleostei: Cyprinodontidae): results of mitochondrial DNA analysis.

Science.gov (United States)

Lüssen, Arne; Falk, Thomas M; Villwock, Wolfgang

2003-10-01

Patterns of molecular genetic differentiation among taxa of the "agassii species complex" (Parenti, 1984) were analysed based on partial mtDNA control region sequences. Special attention has been paid to Chilean populations of Orestias agassii and species from isolated lakes of northern Chile, e.g., O. agassii, Orestias chungarensis, Orestias parinacotensis, Orestias laucaensis, and Orestias ascotanensis. Orestias tschudii, Orestias luteus, and Orestias ispi were analysed comparatively. Our findings support the utility of mtDNA control region sequences for phylogenetic studies within the "agassii species complex" and confirmed the monophyly of this particular lineage, excluding O. luteus. However, the monophyly of further morphologically defined lineages within the "agassii complex" appears doubtful. No support was found for the utility of these data sets for inferring phylogenetic relationships between more distantly related taxa originating from Lake Titicaca.

Genome digging: insight into the mitochondrial genome of Homo.

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Igor V Ovchinnikov

2010-12-01

Full Text Available A fraction of the Neanderthal mitochondrial genome sequence has a similarity with a 5,839-bp nuclear DNA sequence of mitochondrial origin (numt on the human chromosome 1. This fact has never been interpreted. Although this phenomenon may be attributed to contamination and mosaic assembly of Neanderthal mtDNA from short sequencing reads, we explain the mysterious similarity by integration of this numt (mtAncestor-1 into the nuclear genome of the common ancestor of Neanderthals and modern humans not long before their reproductive split.Exploiting bioinformatics, we uncovered an additional numt (mtAncestor-2 with a high similarity to the Neanderthal mtDNA and indicated that both numts represent almost identical replicas of the mtDNA sequences ancestral to the mitochondrial genomes of Neanderthals and modern humans. In the proteins, encoded by mtDNA, the majority of amino acids distinguishing chimpanzees from humans and Neanderthals were acquired by the ancestral hominins. The overall rate of nonsynonymous evolution in Neanderthal mitochondrial protein-coding genes is not higher than in other lineages. The model incorporating the ancestral hominin mtDNA sequences estimates the average divergence age of the mtDNAs of Neanderthals and modern humans to be 450,000-485,000 years. The mtAncestor-1 and mtAncestor-2 sequences were incorporated into the nuclear genome approximately 620,000 years and 2,885,000 years ago, respectively.This study provides the first insight into the evolution of the mitochondrial DNA in hominins ancestral to Neanderthals and humans. We hypothesize that mtAncestor-1 and mtAncestor-2 are likely to be molecular fossils of the mtDNAs of Homo heidelbergensis and a stem Homo lineage. The d(N/d(S dynamics suggests that the effective population size of extinct hominins was low. However, the hominin lineage ancestral to humans, Neanderthals and H. heidelbergensis, had a larger effective population size and possessed genetic diversity

Circulation of influenza B lineages in northern Viet Nam, 2007–2014

Science.gov (United States)

Le, Thi Thanh; Pham, Thu Hang; Pham, Thi Hien; Nguyen, Le Khanh Hang; Hoang, Vu Mai Phuong; Tran, Thu Huong; Nguyen, Vu Son; Ngo, Huong Giang

2015-01-01

Introduction Influenza B viruses circulate throughout Viet Nam, and their activities vary by region. There have been two antigenically distinct lineages of influenza B viruses co-circulating in the past 20 years; however, only one lineage is selected as a component of contemporary trivalent seasonal influenza vaccines. To improve the understanding of circulating influenza B lineages and influenza vaccine mismatches, we report the virus lineages circulating in northern Viet Nam over an eight-year period (2007–2014). Methods Lineages of 331 influenza B viruses were characterized by haemagglutination inhibition assay against standard reference ferret (Yamagata) and sheep (Victoria) antisera. Sequence analysis of the haemagglutinin gene was performed in 64 selected influenza B isolates. Results The proportion of influenza B lineages changed by year. The Yamagata lineage predominated in 2007, 2008 and 2012; the Victoria lineage predominated in 2009–2014 except 2012. The two lineages showed continuous evolution over time. The Northern Hemisphere’s influenza vaccine components were mismatched with the predominant circulating viruses in 2007, 2009 and 2014. Discussion The seasonality of influenza B activity is more variable in tropical and subtropical regions than in temperate zones. Our data showed a common co-circulation of both influenza B lineages in northern Viet Nam, and it was difficult to predict which one was the predominant lineage. Quadrivalent influenza vaccines containing both lineages may improve the effectiveness of influenza vaccine programmes in the future. PMID:26798557

A new view on dam lines in Polish Arabian horses based on mtDNA analysis

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Sell Jerzy

2007-09-01

Full Text Available Abstract Polish Arabian horses are one of the oldest and the most important Arab populations in the world. The Polish Arabian Stud Book and the Genealogical Charts by Skorkowski are the main sources of information on the ancestors of Polish Arabs. Both publications were viewed as credible sources of information until the 1990s when the data regarding one of the dam lines was questioned. The aim of the current study was to check the accuracy of the pedigree data of Polish dam lines using mtDNA analysis. The analyses of a 458 bp mtDNA D-loop fragment from representatives of 15 Polish Arabian dam lines revealed 14 distinct haplotypes. The results were inconsistent with pedigree data in the case of two lines. A detailed analysis of the historical sources was performed to explain these discrepancies. Our study revealed that representatives of different lines shared the same haplotypes. We also noted a genetic identity between some lines founded by Polish mares of unknown origin and lines established by desert-bred mares.

Somatic mitochondrial DNA mutations in cancer escape purifying selection and high pathogenicity mutations lead to the oncocytic phenotype: pathogenicity analysis of reported somatic mtDNA mutations in tumors

International Nuclear Information System (INIS)

Pereira, Luísa; Soares, Pedro; Máximo, Valdemar; Samuels, David C

2012-01-01

The presence of somatic mitochondrial DNA (mtDNA) mutations in cancer cells has been interpreted in controversial ways, ranging from random neutral accumulation of mutations, to positive selection for high pathogenicity, or conversely to purifying selection against high pathogenicity variants as occurs at the population level. Here we evaluated the predicted pathogenicity of somatic mtDNA mutations described in cancer and compare these to the distribution of variations observed in the global human population and all possible protein variations that could occur in human mtDNA. We focus on oncocytic tumors, which are clearly associated with mitochondrial dysfunction. The protein variant pathogenicity was predicted using two computational methods, MutPred and SNPs&GO. The pathogenicity score of the somatic mtDNA variants were significantly higher in oncocytic tumors compared to non-oncocytic tumors. Variations in subunits of Complex I of the electron transfer chain were significantly more common in tumors with the oncocytic phenotype, while variations in Complex V subunits were significantly more common in non-oncocytic tumors. Our results show that the somatic mtDNA mutations reported over all tumors are indistinguishable from a random selection from the set of all possible amino acid variations, and have therefore escaped the effects of purifying selection that act strongly at the population level. We show that the pathogenicity of somatic mtDNA mutations is a determining factor for the oncocytic phenotype. The opposite associations of the Complex I and Complex V variants with the oncocytic and non-oncocytic tumors implies that low mitochondrial membrane potential may play an important role in determining the oncocytic phenotype

'Mitominis': multiplex PCR analysis of reduced size amplicons for compound sequence analysis of the entire mtDNA control region in highly degraded samples.

Science.gov (United States)

Eichmann, Cordula; Parson, Walther

2008-09-01

The traditional protocol for forensic mitochondrial DNA (mtDNA) analyses involves the amplification and sequencing of the two hypervariable segments HVS-I and HVS-II of the mtDNA control region. The primers usually span fragment sizes of 300-400 bp each region, which may result in weak or failed amplification in highly degraded samples. Here we introduce an improved and more stable approach using shortened amplicons in the fragment range between 144 and 237 bp. Ten such amplicons were required to produce overlapping fragments that cover the entire human mtDNA control region. These were co-amplified in two multiplex polymerase chain reactions and sequenced with the individual amplification primers. The primers were carefully selected to minimize binding on homoplasic and haplogroup-specific sites that would otherwise result in loss of amplification due to mis-priming. The multiplexes have successfully been applied to ancient and forensic samples such as bones and teeth that showed a high degree of degradation.

Two hemocyte lineages exist in silkworm larval hematopoietic organ.

Science.gov (United States)

Nakahara, Yuichi; Kanamori, Yasushi; Kiuchi, Makoto; Kamimura, Manabu

2010-07-28

Insects have multiple hemocyte morphotypes with different functions as do vertebrates, however, their hematopoietic lineages are largely unexplored with the exception of Drosophila melanogaster. To study the hematopoietic lineage of the silkworm, Bombyx mori, we investigated in vivo and in vitro differentiation of hemocyte precursors in the hematopoietic organ (HPO) into the four mature hemocyte subsets, namely, plasmatocytes, granulocytes, oenocytoids, and spherulocytes. Five days after implantation of enzymatically-dispersed HPO cells from a GFP-expressing transgenic line into the hemocoel of normal larvae, differentiation into plasmatocytes, granulocytes and oenocytoids, but not spherulocytes, was observed. When the HPO cells were cultured in vitro, plasmatocytes appeared rapidly, and oenocytoids possessing prophenol oxidase activity appeared several days later. HPO cells were also able to differentiate into a small number of granulocytes, but not into spherulocytes. When functionally mature plasmatocytes were cultured in vitro, oenocytoids were observed 10 days later. These results suggest that the hemocyte precursors in HPO first differentiate into plasmatocytes, which further change into oenocytoids. From these results, we propose that B. mori hemocytes can be divided into two major lineages, a granulocyte lineage and a plasmatocyte-oenocytoid lineage. The origins of the spherulocytes could not be determined in this study. We construct a model for the hematopoietic lineages at the larval stage of B. mori.

Evidence of multiple divergent mitochondrial lineages within the ...

African Journals Online (AJOL)

On this basis, the mitochondrial cytochrome c oxidase subunit 1 (COI) was used to reconstruct the phylogeny of Bicoxidens and reveal divergent lineages within the genus. Maximum likelihood and Bayesian inference analyses recovered a paraphyletic Bicoxidens phylogram with divergent lineages present in three species ...

Genome-wide analysis of the human Alu Yb-lineage

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Carter Anthony B

2004-03-01

Full Text Available Abstract The Alu Yb-lineage is a 'young' primarily human-specific group of short interspersed element (SINE subfamilies that have integrated throughout the human genome. In this study, we have computationally screened the draft sequence of the human genome for Alu Yb-lineage subfamily members present on autosomal chromosomes. A total of 1,733 Yb Alu subfamily members have integrated into human autosomes. The average ages of Yb-lineage subfamilies, Yb7, Yb8 and Yb9, are estimated as 4.81, 2.39 and 2.32 million years, respectively. In order to determine the contribution of the Alu Yb-lineage to human genomic diversity, 1,202 loci were analysed using polymerase chain reaction (PCR-based assays, which amplify the genomic regions containing individual Yb-lineage subfamily members. Approximately 20 per cent of the Yb-lineage Alu elements are polymorphic for insertion presence/absence in the human genome. Fewer than 0.5 per cent of the Yb loci also demonstrate insertions at orthologous positions in non-human primate genomes. Genomic sequencing of these unusual loci demonstrates that each of the orthologous loci from non-human primate genomes contains older Y, Sg and Sx Alu family members that have been altered, through various mechanisms, into Yb8 sequences. These data suggest that Alu Yb-lineage subfamily members are largely restricted to the human genome. The high copy number, level of insertion polymorphism and estimated age indicate that members of the Alu Yb elements will be useful in a wide range of genetic analyses.

Ancestral polymorphisms and sex-biased migration shaped the demographic history of brown bears and polar bears.

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Shigeki Nakagome

Full Text Available Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA and matrilineal mitochondrial DNA (mtDNA. Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA or more than 14 times (mtDNA larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA.

Ancestral polymorphisms and sex-biased migration shaped the demographic history of brown bears and polar bears.

Science.gov (United States)

Nakagome, Shigeki; Mano, Shuhei; Hasegawa, Masami

2013-01-01

Recent studies have reported discordant gene trees in the evolution of brown bears and polar bears. Genealogical histories are different among independent nuclear loci and between biparentally inherited autosomal DNA (aDNA) and matrilineal mitochondrial DNA (mtDNA). Based on multi-locus genomic sequences from aDNA and mtDNA, we inferred the population demography of brown and polar bears and found that brown bears have 6 times (aDNA) or more than 14 times (mtDNA) larger population sizes than polar bears and that polar bear lineage is derived from within brown bear diversity. In brown bears, the effective population size ratio of mtDNA to aDNA was at least 0.62, which deviated from the expected value of 0.25, suggesting matriarchal population due to female philopatry and male-biased migration. These results emphasize that ancestral polymorphisms and sex-biased migration may have contributed to conflicting branching patterns in brown and polar bears across aDNA genes and mtDNA.

Genetic uniqueness of the Waorani tribe from the Ecuadorian Amazon.

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Cardoso, S; Alfonso-Sánchez, M A; Valverde, L; Sánchez, D; Zarrabeitia, M T; Odriozola, A; Martínez-Jarreta, B; de Pancorbo, M M

2012-06-01

South America and especially the Amazon basin is known to be home to some of the most isolated human groups in the world. Here, we report on a study of mitochondrial DNA (mtDNA) in the Waorani from Ecuador, probably the most warlike human population known to date. Seeking to look in more depth at the characterization of the genetic diversity of this Native American tribe, molecular markers from the X and Y chromosomes were also analyzed. Only three different mtDNA haplotypes were detected among the Waorani sample. One of them, assigned to Native American haplogroup A2, accounted for more than 94% of the total diversity of the maternal gene pool. Our results for sex chromosome molecular markers failed to find close genetic kinship between individuals, further emphasizing the low genetic diversity of the mtDNA. Bearing in mind the results obtained for both the analysis of the mtDNA control region and complete mitochondrial genomes, we suggest the existence of a 'Waorani-specific' mtDNA lineage. According to current knowledge on the phylogeny of haplogroup A2, we propose that this lineage could be designated as subhaplogroup A2s. Its wide predominance among the Waorani people might have been conditioned by severe genetic drift episodes resulting from founding events, long-term isolation and a traditionally small population size most likely associated with the striking ethnography of this Amazonian community. In all, the Waorani constitute a fine example of how genetic imprint may mirror ethnopsychology and sociocultural features in human populations.

Variations on a theme in fruit development: the PLE lineage of MADS-box genes in tomato (TAGL1) and other species.

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Garceau, Danielle C; Batson, Megan K; Pan, Irvin L

2017-08-01

This article focuses on the role of TOMATO AGAMOUS-LIKE 1 (TAGL1) on a wide range of ripening functions in tomato. We also examine orthologs of this gene in related species that produce different fruit types and discuss some evolutionary implications. TOMATO AGAMOUS-LIKE 1 (TAGL1) is a MADS-box transcription factor gene that belongs to the PLENA (PLE) lineage within the AGAMOUS (AG) clade. The most well-studied genes in this lineage are the SHATTERPROOF (SHP) genes in Arabidopsis, known to be involved in dehiscence zone formation during silique development. In tomato, TAGL1 has been shown to control several aspects of tomato fruit ripening. Most notably, carotenoid synthesis seems to be controlled by TAGL1, likely via the ethylene synthesis and signaling pathway and in combination with RIPENING INHIBITOR (RIN). In addition, TAGL1 regulates genes involved in cell cycle regulation, flavonoid and lignin biosynthesis, and cuticle development. We discuss many of the genes in these different pathways that are likely controlled by TAGL1, directly or indirectly. We also examine the relationship of TAGL1 with known and putative interaction partners. PLE lineage genes have also been examined in other species such as Antirrhinum, Petunia, and Nicotiana and provide an interesting example of conservation and diversification of function in species that produce very different types of fleshy and dry fruits. The control of lignification may be a common mechanism for this group of genes. Lastly, we discuss future work needed to elucidate the TAGL1 regulatory pathway in tomato and to help better understand the functional diversification of genes in this lineage in related species.

Two hemocyte lineages exist in silkworm larval hematopoietic organ.

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Yuichi Nakahara

Full Text Available BACKGROUND: Insects have multiple hemocyte morphotypes with different functions as do vertebrates, however, their hematopoietic lineages are largely unexplored with the exception of Drosophila melanogaster. METHODOLOGY/PRINCIPAL FINDINGS: To study the hematopoietic lineage of the silkworm, Bombyx mori, we investigated in vivo and in vitro differentiation of hemocyte precursors in the hematopoietic organ (HPO into the four mature hemocyte subsets, namely, plasmatocytes, granulocytes, oenocytoids, and spherulocytes. Five days after implantation of enzymatically-dispersed HPO cells from a GFP-expressing transgenic line into the hemocoel of normal larvae, differentiation into plasmatocytes, granulocytes and oenocytoids, but not spherulocytes, was observed. When the HPO cells were cultured in vitro, plasmatocytes appeared rapidly, and oenocytoids possessing prophenol oxidase activity appeared several days later. HPO cells were also able to differentiate into a small number of granulocytes, but not into spherulocytes. When functionally mature plasmatocytes were cultured in vitro, oenocytoids were observed 10 days later. These results suggest that the hemocyte precursors in HPO first differentiate into plasmatocytes, which further change into oenocytoids. CONCLUSIONS/SIGNIFICANCE: From these results, we propose that B. mori hemocytes can be divided into two major lineages, a granulocyte lineage and a plasmatocyte-oenocytoid lineage. The origins of the spherulocytes could not be determined in this study. We construct a model for the hematopoietic lineages at the larval stage of B. mori.

Bacillus anthracis in China and its relationship to worldwide lineages

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Schupp James M

2009-04-01

Full Text Available Abstract Background The global pattern of distribution of 1033 B. anthracis isolates has previously been defined by a set of 12 conserved canonical single nucleotide polymorphisms (canSNP. These studies reinforced the presence of three major lineages and 12 sub-lineages and sub-groups of this anthrax-causing pathogen. Isolates that form the A lineage (unlike the B and C lineages have become widely dispersed throughout the world and form the basis for the geographical disposition of "modern" anthrax. An archival collection of 191 different B. anthracis isolates from China provides a glimpse into the possible role of Chinese trade and commerce in the spread of certain sub-lineages of this pathogen. Canonical single nucleotide polymorphism (canSNP and multiple locus VNTR analysis (MLVA typing has been used to examine this archival collection of isolates. Results The canSNP study indicates that there are 5 different sub-lineages/sub-groups in China out of 12 previously described world-wide canSNP genotypes. Three of these canSNP genotypes were only found in the western-most province of China, Xinjiang. These genotypes were A.Br.008/009, a sub-group that is spread across most of Europe and Asia; A.Br.Aust 94, a sub-lineage that is present in Europe and India, and A.Br.Vollum, a lineage that is also present in Europe. The remaining two canSNP genotypes are spread across the whole of China and belong to sub-group A.Br.001/002 and the A.Br.Ames sub-lineage, two closely related genotypes. MLVA typing adds resolution to the isolates in each canSNP genotype and diversity indices for the A.Br.008/009 and A.Br.001/002 sub-groups suggest that these represent older and established clades in China. Conclusion B. anthracis isolates were recovered from three canSNP sub-groups (A.Br.008/009, A.Br.Aust94, and A.Br.Vollum in the western most portion of the large Chinese province of Xinjiang. The city of Kashi in this province appears to have served as a crossroads

MtDNA and nuclear data reveal patterns of low genetic differentiation for the isopods Stenosoma lancifer and Stenosoma acuminatum, with low dispersal ability along the northeast Atlantic coast

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Raquel Xavier

2011-11-01

Full Text Available Evidence for a general lack of genetic differentiation of intertidal invertebrate assemblages in the North Atlantic, based on mtDNA sequence variation, has been interpreted as resulting from recent colonization following the Last Glacial Maximum. In the present study, the phylogeographic patterns of one nuclear and one mtDNA gene fragments of two isopods, Stenosoma lancifer (Miers, 1881 and Stenosoma acuminatum Leach, 1814, from the northeast Atlantic were investigated. These organisms have direct development, which makes them poor dispersers, and are therefore expected to maintain signatures of past historical events in their genomes. Lack of genetic structure, significant deviations from neutrality and star-like haplotype networks have been observed for both mtDNA and nuclear markers of S. lancifer, as well as for the mtDNA of S. acuminatum. No sequence variation was observed for the nuclear gene fragment of S. acuminatum. These results suggest a scenario of recent colonization and demographic expansion and/or high population connectivity driven by ocean currents and sporadic long-distance dispersal through rafting.

Stem Cell Lineages: Between Cell and Organism

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Melinda Bonnie Fagan

2017-01-01

Full Text Available Ontologies of living things are increasingly grounded on the concepts and practices of current life science. Biological development is a process, undergone by living things, which begins with a single cell and (in an important class of cases ends with formation of a multicellular organism. The process of development is thus prima facie central for ideas about biological individuality and organismality. However, recent accounts of these concepts do not engage developmental biology. This paper aims to fill the gap, proposing the lineage view of stem cells as an ontological framework for conceptualizing organismal development. This account is grounded on experimental practices of stem cell research, with emphasis on new techniques for generating biological organization in vitro. On the lineage view, a stem cell is the starting point of a cell lineage with a specific organismal source, time-interval of existence, and ‘tree topology’ of branch-points linking the stem to developmental termini. The concept of ‘enkapsis’ accommodates the cell-organism relation within the lineage view; this hierarchical notion is further explicated by considering the methods and results of stem cell experiments. Results of this examination include a (partial characterization of stem cells’ developmental versatility, and the context-dependence of developmental processes involving stem cells.

Determining Lineage Pathways from Cellular Barcoding Experiments

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Leïla Perié

2014-02-01

Full Text Available Cellular barcoding and other single-cell lineage-tracing strategies form experimental methodologies for analysis of in vivo cell fate that have been instrumental in several significant recent discoveries. Due to the highly nonlinear nature of proliferation and differentiation, interrogation of the resulting data for evaluation of potential lineage pathways requires a new quantitative framework complete with appropriate statistical tests. Here, we develop such a framework, illustrating its utility by analyzing data from barcoded multipotent cells of the blood system. This application demonstrates that the data require additional paths beyond those found in the classical model, which leads us to propose that hematopoietic differentiation follows a loss of potential mechanism and to suggest further experiments to test this deduction. Our quantitative framework can evaluate the compatibility of lineage trees with barcoded data from any proliferating and differentiating cell system.

Feather barbs as a good source of mtDNA for bird species identification in forensic wildlife investigations.

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Speller, Camilla F; Nicholas, George P; Yang, Dongya Y

2011-07-28

The ability to accurately identify bird species is crucial for wildlife law enforcement and bird-strike investigations. However, such identifications may be challenging when only partial or damaged feathers are available for analysis. By applying vigorous contamination controls and sensitive PCR amplification protocols, we found that it was feasible to obtain accurate mitochondrial (mt)DNA-based species identification with as few as two feather barbs. This minimally destructive DNA approach was successfully used and tested on a variety of bird species, including North American wild turkey (Meleagris gallopavo), Canada goose (Branta canadensis), blue heron (Ardea herodias) and pygmy owl (Glaucidium californicum). The mtDNA was successfully obtained from 'fresh' feathers, historic museum specimens and archaeological samples, demonstrating the sensitivity and versatility of this technique. By applying appropriate contamination controls, sufficient quantities of mtDNA can be reliably recovered and analyzed from feather barbs. This previously overlooked substrate provides new opportunities for accurate DNA species identification when minimal feather samples are available for forensic analysis.

A Signal, from Human mtDNA, of Postglacial Recolonization in Europe

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Torroni, Antonio; Bandelt, Hans-Jürgen; Macaulay, Vincent; Richards, Martin; Cruciani, Fulvio; Rengo, Chiara; Martinez-Cabrera, Vicente; Villems, Richard; Kivisild, Toomas; Metspalu, Ene; Parik, Jüri; Tolk, Helle-Viivi; Tambets, Kristiina; Forster, Peter; Karger, Bernd; Francalacci, Paolo; Rudan, Pavao; Janicijevic, Branka; Rickards, Olga; Savontaus, Marja-Liisa; Huoponen, Kirsi; Laitinen, Virpi; Koivumäki, Satu; Sykes, Bryan; Hickey, Eileen; Novelletto, Andrea; Moral, Pedro; Sellitto, Daniele; Coppa, Alfredo; Al-Zaheri, Nadia; Santachiara-Benerecetti, A. Silvana; Semino, Ornella; Scozzari, Rosaria

2001-01-01

Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T→C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed “pre*V,” since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory. PMID:11517423

Phylogeography of the common vampire bat (Desmodus rotundus: Marked population structure, Neotropical Pleistocene vicariance and incongruence between nuclear and mtDNA markers

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Morgante João S

2009-12-01

Full Text Available Abstract Background The common vampire bat Desmodus rotundus is an excellent model organism for studying ecological vicariance in the Neotropics due to its broad geographic range and its preference for forested areas as roosting sites. With the objective of testing for Pleistocene ecological vicariance, we sequenced a mitocondrial DNA (mtDNA marker and two nuclear markers (RAG2 and DRB to try to understand how Pleistocene glaciations affected the distribution of intraspecific lineages in this bat. Results Five reciprocally monophyletic clades were evident in the mitochondrial gene tree, and in most cases with high bootstrap support: Central America (CA, Amazon and Cerrado (AMC, Pantanal (PAN, Northern Atlantic Forest (NAF and Southern Atlantic Forest (SAF. The Atlantic forest clades formed a monophyletic clade with high bootstrap support, creating an east/west division for this species in South America. On the one hand, all coalescent and non-coalescent estimates point to a Pleistocene time of divergence between the clades. On the other hand, the nuclear markers showed extensive sharing of haplotypes between distant localities, a result compatible with male-biased gene flow. In order to test if the disparity between the mitochondrial and nuclear markers was due to the difference in mutation rate and effective size, we performed a coalescent simulation to examine the feasibility that, given the time of separation between the observed lineages, even with a gene flow rate close to zero, there would not be reciprocal monophyly for a neutral nuclear marker. We used the observed values of theta and an estimated mutation rate for the nuclear marker gene to perform 1000 iterations of the simulation. The results of this simulation were inconclusive: the number of iterations with and without reciprocal monophyly of one or more clades are similar. Conclusions We therefore conclude that the pattern exhibited by the common vampire bat, with marked

Rozmanitost projevů heteroplazmické mtDNA mutace 8993 T>G ve dvou rodinách

Czech Academy of Sciences Publication Activity Database

Tesařová, M.; Hansíková, H.; Hlavatá, A.; Klement, P.; Houšťková, H.; Houštěk, Josef; Zeman, J.

2002-01-01

Roč. 141, č. 17 (2002), s. 551-554 ISSN 0008-7335 R&D Projects: GA MZd(CZ) NE6533; GA MZd(CZ) NE6555; GA MŠk(CZ) LN00A079 Institutional research plan: CEZ:AV0Z5011922 Keywords : NARP syndrome * mtDNA mutation 8993 T>G Subject RIV: EB - Genetics ; Molecular Biology

Protection of horses from West Nile virus Lineage 2 challenge following immunization with a whole, inactivated WNV lineage 1 vaccine.

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Bowen, Richard A; Bosco-Lauth, Angela; Syvrud, Kevin; Thomas, Anne; Meinert, Todd R; Ludlow, Deborah R; Cook, Corey; Salt, Jeremy; Ons, Ellen

2014-09-22

Over the last years West Nile virus (WNV) lineage 2 has spread from the African to the European continent. This study was conducted to demonstrate efficacy of an inactivated, lineage 1-based, WNV vaccine (Equip WNV) against intrathecal challenge of horses with a recent isolate of lineage 2 WNV. Twenty horses, sero-negative for WNV, were enrolled and were randomly allocated to one of two treatment groups: an unvaccinated control group (T01, n=10) and a group administered with Equip WNV (T02, n=10). Horses were vaccinated at Day 0 and 21 and were challenged at day 42 with WNV lineage 2, Nea Santa/Greece/2010. Personnel performing clinical observations were blinded to treatment allocation. Sixty percent of the controls had to be euthanized after challenge compared to none of the vaccinates. A significantly lower percentage of the vaccinated animals showed clinical disease (two different clinical observations present on the same day) on six different days of study and the percentage of days with clinical disease was significantly lower in the vaccinated group. A total of 80% of the non-vaccinated horses showed viremia while only one vaccinated animal was positive by virus isolation on a single occasion. Vaccinated animals started to develop antibodies against WNV lineage 2 from day 14 (2 weeks after the first vaccination) and at day 42 (the time of onset of immunity) they had all developed a strong antibody response. Histopathology scores for all unvaccinated animals ranged from mild to very severe in each of the tissues examined (cervical spinal cord, medulla and pons), whereas in vaccinated horses 8 of 10 animals had no lesions and 2 had minimal lesions in one tissue. In conclusion, Equip WNV significantly reduced the number of viremic horses, the duration and severity of clinical signs of disease and mortality following challenge with lineage 2 WNV. Copyright © 2014 Elsevier Ltd. All rights reserved.

Association between Mycobacterium tuberculosis lineage and site of disease in Florida, 2009-2015.

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Séraphin, Marie Nancy; Doggett, Richard; Johnston, Lori; Zabala, Jose; Gerace, Alexandra M; Lauzardo, Michael

2017-11-01

Mycobacterium tuberculosis is characterized into four global lineages with strong geographical restriction. To date one study in the United States has investigated M. tuberculosis lineage association with tuberculosis (TB) disease presentation (extra-pulmonary versus pulmonary). We update this analysis using recent (2009-2015) data from the State of Florida to measure lineage association with pulmonary TB, the infectious form of the disease. M. tuberculosis lineage was assigned based on the spacer oligonucleotide typing (spoligotyping) patterns. TB disease site was defined as exclusively pulmonary or extra-pulmonary. We used ORs to measure the association between M. tuberculosis lineages and pulmonary compared to extra-pulmonary TB. The final multivariable model was adjusted for patient socio-demographics, HIV and diabetes status. We analyzed 3061 cases, 83.4% were infected with a Euro-American lineage, 8.4% Indo-Oceanic and 8.2% East-Asian lineage. The majority of the cases (86.0%) were exclusively pulmonary. Compared to the Indo-Oceanic lineage, infection with a Euro-American (AOR=1.87, 95% CI: 1.21, 2.91) or an East-Asian (AOR=2.11, 95% CI: 1.27, 3.50) lineage favored pulmonary disease compared to extra-pulmonary. In a sub-analysis among pulmonary cases, strain lineage was not associated with sputum smear positive status, indicating that the observed association with pulmonary disease is independent of host contagiousness. As an obligate pathogen, M. tuberculosis' fitness is directly correlated to its transmission potential. In this analysis, we show that M. tuberculosis lineage is associated with pulmonary disease presentation. This association may explain the predominance in a region of certain lineages compared to others. Copyright © 2017 Elsevier B.V. All rights reserved.

Hybridization levels in European Sus scrofa, comparison between genetic and survey data

DEFF Research Database (Denmark)

Iacolina, Laura; Bakan, Jana; Cubric-Curik, Vlatka

2016-01-01

are biparentally inherited, thus representing the whole population, while mtDNA only shows the maternal lineage. In recent years the development and decrease in price of genomics techniques have allowed the implementation of genomic markers (like whole genome sequencing or Single Nucleotide Polymorphisms - SNP......) have been reported in several European countries and might provide insight on human practices that can lead to increased, although spatially delimited, risk of contagion. The markers most commonly used to investigate this aspect are mitochondrial DNA (mtDNA), MC1R and microsatellite (STR). All of them...... present some advantages and some disadvantages. MtDNA and MC1R can be easily compared among laboratories, while STR require calibration. Furthermore, STR can only detect recent hybridization events, while MC1R and mtDNA can also identify more ancient episodes. On the other hand STR and MC1R...

Minisequencing mitochondrial DNA pathogenic mutations

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Carracedo Ángel

2008-04-01

Full Text Available Abstract Background There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations. Methods We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease. Results We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G>A and m.14484T>C occur at higher frequency than expected by change in the Galician (northwest Spain patients carrying haplogroup J lineages (Fisher's Exact test, P-value Conclusion We here developed a minisequencing genotyping method for the screening of the most common pathogenic mtDNA mutations which is simple, fast, and low-cost. The technique is robust and reproducible and can easily be implemented in standard clinical laboratories.

Cell lineages of the embryo of the nematode Caenorhabditis elegans.

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Deppe, U; Schierenberg, E; Cole, T; Krieg, C; Schmitt, D; Yoder, B; von Ehrenstein, G

1978-01-01

Embryogenesis of the free-living soil nematode Caenorhabditis elegans produces a juvenile having about 550 cells at hatching. We have determined the lineages of 182 cells by tracing the divisions of individual cells in living embryos. An invariant pattern of cleavage divisions of the egg generates a set of stem cells. These stem cells are the founders of six stem cell lineages. Each lineage has its own clock--i.e., an autonomous rhythm of synchronous cell divisions. The rhythms are maintained in spite of extensive cellular rearrangement. The rate and the orientation of the cell divisions of the cell lineages are essentially invariant among individuals. Thus, the destiny of cells seems to depend primarily on their lineage history. The anterior position of the site of origin of the stem cells in the egg relates to the rate of the cell cycle clock, suggesting intracellular preprogramming of the uncleaved egg. We used a technique that allows normal embryogenesis, from the fertilized egg to hatching, outside the parent under a cover glass. Embryogenesis was followed microscopically with Nomarski interference optics and high-resolution video recording.

Global DNA methylation synergistically regulates the nuclear and mitochondrial genomes in glioblastoma cells.

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Sun, Xin; Johnson, Jacqueline; St John, Justin C

2018-05-02

Replication of mitochondrial DNA is strictly regulated during differentiation and development allowing each cell type to acquire its required mtDNA copy number to meet its specific needs for energy. Undifferentiated cells establish the mtDNA set point, which provides low numbers of mtDNA copy but sufficient template for replication once cells commit to specific lineages. However, cancer cells, such as those from the human glioblastoma multiforme cell line, HSR-GBM1, cannot complete differentiation as they fail to enforce the mtDNA set point and are trapped in a 'pseudo-differentiated' state. Global DNA methylation is likely to be a major contributing factor, as DNA demethylation treatments promote differentiation of HSR-GBM1 cells. To determine the relationship between DNA methylation and mtDNA copy number in cancer cells, we applied whole genome MeDIP-Seq and RNA-Seq to HSR-GBM1 cells and following their treatment with the DNA demethylation agents 5-azacytidine and vitamin C. We identified key methylated regions modulated by the DNA demethylation agents that also induced synchronous changes to mtDNA copy number and nuclear gene expression. Our findings highlight the control exerted by DNA methylation on the expression of key genes, the regulation of mtDNA copy number and establishment of the mtDNA set point, which collectively contribute to tumorigenesis.

Molecular Characterization of Sudanese and Southern Sudanese Chicken Breeds Using mtDNA D-Loop

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Charles E. Wani

2014-01-01

Full Text Available The objective of this study was to assess the genetic relationships and diversity and to estimate the amount of gene flow among the five chicken populations from Sudan and South Sudan and commercial strain of egg line White Leghorn chickens. The chicken populations were genotyped using mtDNA D-loop as a molecular marker. PCR product of the mtDNA D-loop segment was 600 bp and 14 haplotypes were identified. The neighbor-joining phylogenetic tree indicated that the indigenous Sudanese chickens can be grouped into two clades, IV and IIIa only. Median joining networks analysis showed that haplotype LBB49 has the highest frequency. The hierarchal analysis of molecular variance (AMOVA showed that genetic variation within the population was 88.6% and the differentiation among the population was 11.4%. When the populations was redefined into two geographical zones, rich and poor Savanna, the results were fractioned into three genetic variations: between individuals within population 95.5%, between populations within the group 0.75%, and genetic variation between groups 3.75%. The pair wise Fst showed high genetic difference between Betwil populations and the rest with Fst ranging from 0.1492 to 0.2447. We found that there is large number of gene exchanges within the Sudanese indigenous chicken (Nm=4.622.

Fast and scalable inference of multi-sample cancer lineages.

KAUST Repository

Popic, Victoria; Salari, Raheleh; Hajirasouliha, Iman; Kashef-Haghighi, Dorna; West, Robert B; Batzoglou, Serafim

2015-01-01

Somatic variants can be used as lineage markers for the phylogenetic reconstruction of cancer evolution. Since somatic phylogenetics is complicated by sample heterogeneity, novel specialized tree-building methods are required for cancer phylogeny reconstruction. We present LICHeE (Lineage Inference for Cancer Heterogeneity and Evolution), a novel method that automates the phylogenetic inference of cancer progression from multiple somatic samples. LICHeE uses variant allele frequencies of somatic single nucleotide variants obtained by deep sequencing to reconstruct multi-sample cell lineage trees and infer the subclonal composition of the samples. LICHeE is open source and available at http://viq854.github.io/lichee .

Fast and scalable inference of multi-sample cancer lineages.

KAUST Repository

Popic, Victoria

2015-05-06

Somatic variants can be used as lineage markers for the phylogenetic reconstruction of cancer evolution. Since somatic phylogenetics is complicated by sample heterogeneity, novel specialized tree-building methods are required for cancer phylogeny reconstruction. We present LICHeE (Lineage Inference for Cancer Heterogeneity and Evolution), a novel method that automates the phylogenetic inference of cancer progression from multiple somatic samples. LICHeE uses variant allele frequencies of somatic single nucleotide variants obtained by deep sequencing to reconstruct multi-sample cell lineage trees and infer the subclonal composition of the samples. LICHeE is open source and available at http://viq854.github.io/lichee .

Lineage Switching in Acute Leukemias: A Consequence of Stem Cell Plasticity?

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Elisa Dorantes-Acosta

2012-01-01

Full Text Available Acute leukemias are the most common cancer in childhood and characterized by the uncontrolled production of hematopoietic precursor cells of the lymphoid or myeloid series within the bone marrow. Even when a relatively high efficiency of therapeutic agents has increased the overall survival rates in the last years, factors such as cell lineage switching and the rise of mixed lineages at relapses often change the prognosis of the illness. During lineage switching, conversions from lymphoblastic leukemia to myeloid leukemia, or vice versa, are recorded. The central mechanisms involved in these phenomena remain undefined, but recent studies suggest that lineage commitment of plastic hematopoietic progenitors may be multidirectional and reversible upon specific signals provided by both intrinsic and environmental cues. In this paper, we focus on the current knowledge about cell heterogeneity and the lineage switch resulting from leukemic cells plasticity. A number of hypothetical mechanisms that may inspire changes in cell fate decisions are highlighted. Understanding the plasticity of leukemia initiating cells might be fundamental to unravel the pathogenesis of lineage switch in acute leukemias and will illuminate the importance of a flexible hematopoietic development.

Phylogeny and temporal diversification of darters (Percidae: Etheostomatinae).

Science.gov (United States)

Near, Thomas J; Bossu, Christen M; Bradburd, Gideon S; Carlson, Rose L; Harrington, Richard C; Hollingsworth, Phillip R; Keck, Benjamin P; Etnier, David A

2011-10-01

Discussions aimed at resolution of the Tree of Life are most often focused on the interrelationships of major organismal lineages. In this study, we focus on the resolution of some of the most apical branches in the Tree of Life through exploration of the phylogenetic relationships of darters, a species-rich clade of North American freshwater fishes. With a near-complete taxon sampling of close to 250 species, we aim to investigate strategies for efficient multilocus data sampling and the estimation of divergence times using relaxed-clock methods when a clade lacks a fossil record. Our phylogenetic data set comprises a single mitochondrial DNA (mtDNA) gene and two nuclear genes sampled from 245 of the 248 darter species. This dense sampling allows us to determine if a modest amount of nuclear DNA sequence data can resolve relationships among closely related animal species. Darters lack a fossil record to provide age calibration priors in relaxed-clock analyses. Therefore, we use a near-complete species-sampled phylogeny of the perciform clade Centrarchidae, which has a rich fossil record, to assess two distinct strategies of external calibration in relaxed-clock divergence time estimates of darters: using ages inferred from the fossil record and molecular evolutionary rate estimates. Comparison of Bayesian phylogenies inferred from mtDNA and nuclear genes reveals that heterospecific mtDNA is present in approximately 12.5% of all darter species. We identify three patterns of mtDNA introgression in darters: proximal mtDNA transfer, which involves the transfer of mtDNA among extant and sympatric darter species, indeterminate introgression, which involves the transfer of mtDNA from a lineage that cannot be confidently identified because the introgressed haplotypes are not clearly referable to mtDNA haplotypes in any recognized species, and deep introgression, which is characterized by species diversification within a recipient clade subsequent to the transfer of

Molecular evidence for long-distance colonization in an Indo-Pacific seahorse lineage

NARCIS (Netherlands)

Teske, PR; Hamilton, H; Palsboll, PJ; Choo, CK; Gabr, H; Lourie, SA; Santos, M; Sreepada, A; Cherry, MI; Matthee, CA

2005-01-01

Mitochondrial control region (mtDNA CR) diversity within and among 6 seahorse populations associated with the Indo-Pacific Hippocampus kuda complex (H. kuda from India, Malaysia, Indonesia and the Philippines, H. fuscus from the Red Sea and H. capensis from South Africa) was compared to determine

Selfish little circles: transmission bias and evolution of large deletion-bearing mitochondrial DNA in Caenorhabditis briggsae nematodes.

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Katie A Clark

Full Text Available Selfish DNA poses a significant challenge to genome stability and organismal fitness in diverse eukaryotic lineages. Although selfish mitochondrial DNA (mtDNA has known associations with cytoplasmic male sterility in numerous gynodioecious plant species and is manifested as petite mutants in experimental yeast lab populations, examples of selfish mtDNA in animals are less common. We analyzed the inheritance and evolution of mitochondrial DNA bearing large heteroplasmic deletions including nad5 gene sequences (nad5Δ mtDNA, in the nematode Caenorhabditis briggsae. The deletion is widespread in C. briggsae natural populations and is associated with deleterious organismal effects. We studied the inheritance patterns of nad5Δ mtDNA using eight sets of C. briggsae mutation-accumulation (MA lines, each initiated from a different natural strain progenitor and bottlenecked as single hermaphrodites across generations. We observed a consistent and strong drive toward higher levels of deletion-bearing molecules in the heteroplasmic pool of mtDNA after ten generations of bottlenecking. Our results demonstrate a uniform transmission bias whereby nad5Δ mtDNA accumulates to higher levels relative to intact mtDNA in multiple genetically diverse natural strains of C. briggsae. We calculated an average 1% per-generation transmission bias for deletion-bearing mtDNA relative to intact genomes. Our study, coupled with known deleterious phenotypes associated with high deletion levels, shows that nad5Δ mtDNA are selfish genetic elements that have evolved in natural populations of C. briggsae, offering a powerful new system to study selfish mtDNA dynamics in metazoans.

Selfish Little Circles: Transmission Bias and Evolution of Large Deletion-Bearing Mitochondrial DNA in Caenorhabditis briggsae Nematodes

Science.gov (United States)

Clark, Katie A.; Howe, Dana K.; Gafner, Kristin; Kusuma, Danika; Ping, Sita; Estes, Suzanne; Denver, Dee R.

2012-01-01

Selfish DNA poses a significant challenge to genome stability and organismal fitness in diverse eukaryotic lineages. Although selfish mitochondrial DNA (mtDNA) has known associations with cytoplasmic male sterility in numerous gynodioecious plant species and is manifested as petite mutants in experimental yeast lab populations, examples of selfish mtDNA in animals are less common. We analyzed the inheritance and evolution of mitochondrial DNA bearing large heteroplasmic deletions including nad5 gene sequences (nad5Δ mtDNA), in the nematode Caenorhabditis briggsae. The deletion is widespread in C. briggsae natural populations and is associated with deleterious organismal effects. We studied the inheritance patterns of nad5Δ mtDNA using eight sets of C. briggsae mutation-accumulation (MA) lines, each initiated from a different natural strain progenitor and bottlenecked as single hermaphrodites across generations. We observed a consistent and strong drive toward higher levels of deletion-bearing molecules in the heteroplasmic pool of mtDNA after ten generations of bottlenecking. Our results demonstrate a uniform transmission bias whereby nad5Δ mtDNA accumulates to higher levels relative to intact mtDNA in multiple genetically diverse natural strains of C. briggsae. We calculated an average 1% per-generation transmission bias for deletion-bearing mtDNA relative to intact genomes. Our study, coupled with known deleterious phenotypes associated with high deletion levels, shows that nad5Δ mtDNA are selfish genetic elements that have evolved in natural populations of C. briggsae, offering a powerful new system to study selfish mtDNA dynamics in metazoans. PMID:22859984

Trophoblast lineage cells derived from human induced pluripotent stem cells

International Nuclear Information System (INIS)

Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard

2013-01-01

Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro

Trophoblast lineage cells derived from human induced pluripotent stem cells

Energy Technology Data Exchange (ETDEWEB)

Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

2013-07-12

Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

Lineage plasticity-mediated therapy resistance in prostate cancer.

Science.gov (United States)

Blee, Alexandra M; Huang, Haojie

2018-06-12

Therapy resistance is a significant challenge for prostate cancer treatment in clinic. Although targeted therapies such as androgen deprivation and androgen receptor (AR) inhibition are effective initially, tumor cells eventually evade these strategies through multiple mechanisms. Lineage reprogramming in response to hormone therapy represents a key mechanism that is increasingly observed. The studies in this area have revealed specific combinations of alterations present in adenocarcinomas that provide cells with the ability to transdifferentiate and perpetuate AR-independent tumor growth after androgen-based therapies. Interestingly, several master regulators have been identified that drive plasticity, some of which also play key roles during development and differentiation of the cell lineages in the normal prostate. Thus, further study of each AR-independent tumor type and understanding underlying mechanisms are warranted to develop combinational therapies that combat lineage plasticity in prostate cancer.

Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage.

Science.gov (United States)

Merker, Matthias; Blin, Camille; Mona, Stefano; Duforet-Frebourg, Nicolas; Lecher, Sophie; Willery, Eve; Blum, Michael G B; Rüsch-Gerdes, Sabine; Mokrousov, Igor; Aleksic, Eman; Allix-Béguec, Caroline; Antierens, Annick; Augustynowicz-Kopeć, Ewa; Ballif, Marie; Barletta, Francesca; Beck, Hans Peter; Barry, Clifton E; Bonnet, Maryline; Borroni, Emanuele; Campos-Herrero, Isolina; Cirillo, Daniela; Cox, Helen; Crowe, Suzanne; Crudu, Valeriu; Diel, Roland; Drobniewski, Francis; Fauville-Dufaux, Maryse; Gagneux, Sébastien; Ghebremichael, Solomon; Hanekom, Madeleine; Hoffner, Sven; Jiao, Wei-wei; Kalon, Stobdan; Kohl, Thomas A; Kontsevaya, Irina; Lillebæk, Troels; Maeda, Shinji; Nikolayevskyy, Vladyslav; Rasmussen, Michael; Rastogi, Nalin; Samper, Sofia; Sanchez-Padilla, Elisabeth; Savic, Branislava; Shamputa, Isdore Chola; Shen, Adong; Sng, Li-Hwei; Stakenas, Petras; Toit, Kadri; Varaine, Francis; Vukovic, Dragana; Wahl, Céline; Warren, Robin; Supply, Philip; Niemann, Stefan; Wirth, Thierry

2015-03-01

Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.

Genetic revision of Caucasian barbels, the genus Barbus: one species plus, one species minus

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Boris A. Levin

2015-11-01

Full Text Available The Eurasian barbs, the genus Barbus, are distributed mainly in drainages of Mediterranean, Black and Caspian Sea basins. The barbels are one of the common fish in the rivers of the Caucasus Mountains situated between Black and Caspian Seas. Despite most of Caucasian Barbus species were already studied phylogenetically by mtDNA marker cytb, the samples used in these studies were represented by one-two specimens. We sampled Caucasian rivers more intensively and checked all main drainages as well as several isolated rivers of Eastern Black Sea drainage (n = 104. Phylogenetic analysis based on two markers of mtDNA (COI and cytb has confirmed four lineages previously reported in Caucasian rivers: B. ciscaucasicus, B. cyri, B. escherichii, and B. kubanicus as well as revealed a new lineage, locally distributed in rivers of Eastern part of Black Sea drainage. Probably new lineage is associated with B. rionicus that was synonymized previously with B. escherichii. The Sevan barbel B. goktschaicus is identical to B. cyri, and we consider the former as conspecific with the latter. Due to extended geographic coverage, we also clarified current ranges of species based on both genetic and morphologic analyses.

Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage.

OpenAIRE

Merker Matthias; Blin Camille; Mona Stefano; Duforet-Frebourg Nicolas; Lecher Sophie; Willery Eve; Blum Michael G B; Rüsch-Gerdes Sabine; Mokrousov Igor; Aleksic Eman; Allix-Béguec Caroline; Antierens Annick; Augustynowicz-Kopec Ewa; Ballif Marie; Barletta Francesca

2015-01-01

International audience; Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiat...

Microsatellite genotyping of medieval cattle from central Italy suggests an old origin of Chianina and Romagnola cattle

NARCIS (Netherlands)

Gargani, Maria; Pariset, Lorraine; Lenstra, Johannes A; De Minicis, Elisabetta; Valentini, Alessio

2015-01-01

Analysis of DNA from archeological remains is a valuable tool to interpret the history of ancient animal populations. So far most studies of ancient DNA target mitochondrial DNA (mtDNA), which reveals maternal lineages, but only partially the relationships of current breeds and ancient populations.

Of mice and (Viking?) men: phylogeography of British and Irish house mice.

Science.gov (United States)

Searle, Jeremy B; Jones, Catherine S; Gündüz, Islam; Scascitelli, Moira; Jones, Eleanor P; Herman, Jeremy S; Rambau, R Victor; Noble, Leslie R; Berry, R J; Giménez, Mabel D; Jóhannesdóttir, Fríoa

2009-01-22

The west European subspecies of house mouse (Mus musculus domesticus) has gained much of its current widespread distribution through commensalism with humans. This means that the phylogeography of M. m. domesticus should reflect patterns of human movements. We studied restriction fragment length polymorphism (RFLP) and DNA sequence variations in mouse mitochondrial (mt) DNA throughout the British Isles (328 mice from 105 localities, including previously published data). There is a major mtDNA lineage revealed by both RFLP and sequence analyses, which is restricted to the northern and western peripheries of the British Isles, and also occurs in Norway. This distribution of the 'Orkney' lineage fits well with the sphere of influence of the Norwegian Vikings and was probably generated through inadvertent transport by them. To form viable populations, house mice would have required large human settlements such as the Norwegian Vikings founded. The other parts of the British Isles (essentially most of mainland Britain) are characterized by house mice with different mtDNA sequences, some of which are also found in Germany, and which probably reflect both Iron Age movements of people and mice and earlier development of large human settlements. MtDNA studies on house mice have the potential to reveal novel aspects of human history.

Glacial cycles as an allopatric speciation pump in north-eastern American freshwater fishes.

Science.gov (United States)

April, Julien; Hanner, Robert H; Dion-Côté, Anne-Marie; Bernatchez, Louis

2013-01-01

Allopatric speciation may be the principal mechanism generating new species. Yet, it remains difficult to judge the generality of this process because few studies have provided evidence that geographic isolation has triggered the development of reproductive isolation over multiple species of a regional fauna. Here, we first combine results from new empirical data sets (7 taxa) and published literature (9 taxa) to show that the eastern Great Lakes drainage represents a multispecies suture zone for glacial lineages of freshwater fishes with variable levels of genetic divergence. Second, we performed amplified fragment length polymorphism analyses among four pairs of lineages. Results indicate that lineages with relatively deep levels of mtDNA 5' COI (barcode) sequence divergence (>2%) developed strong reproductive barriers, while lineages with lower levels of divergence show weaker reproductive isolation when found in sympatry. This suggests that a threshold of 2% sequence divergence at mtDNA could be used as a first step to flag cryptic species in North American freshwater fishes. By describing different levels of divergence and reproductive isolation in different co-occurring fishes, we offer strong evidence that allopatric speciation has contributed significantly to the diversification of north-eastern American freshwater fishes and confirm that Pleistocene glacial cycles can be viewed as a 'speciation pump' that played a predominant role in generating biodiversity. © 2012 Blackwell Publishing Ltd.

Structure elucidation of secondary natural products

International Nuclear Information System (INIS)

Seger, C.

2001-06-01

The presented thesis deals with the structure elucidation of secondary natural products. Most of the compounds under investigation were terpenes, especially triterpenes, alkaloids and stilbenoids. Besides characterizing a multitude of already known and also new compounds, it was possible to detect and correct wrongly assigned literature data. The methodological aspect of this thesis lies - beside in the utilization of modern 2D NMR spectroscopy - in the evaluation of computer assisted structure elucidation (CASE) techniques in the course of spectroscopy supported structure elucidation processes. (author)

The first fossil of a bolbitidoid fern belongs to the early-divergent lineages of Elaphoglossum (Dryopteridaceae).

Science.gov (United States)

Lóriga, Josmaily; Schmidt, Alexander R; Moran, Robbin C; Feldberg, Kathrin; Schneider, Harald; Heinrichs, Jochen

2014-09-01

• Closing gaps in the fossil record and elucidating phylogenetic relationships of mostly incomplete fossils are major challenges in the reconstruction of the diversification of fern lineages through time. The cosmopolitan family Dryopteridaceae represents one of the most species-rich families of leptosporangiate ferns, yet its fossil record is sparse and poorly understood. Here, we describe a fern inclusion in Miocene Dominican amber and investigate its relationships to extant Dryopteridaceae.• The morphology of the fossil was compared with descriptions of extant ferns, resulting in it being tentatively assigned to the bolbitidoid fern genus Elaphoglossum. This assignment was confirmed by reconstructing the evolution of the morphological characters preserved in the inclusion on a molecular phylogeny of 158 extant bolbitidoid ferns. To assess the morphology-based assignment of the fossil to Elaphoglossum, we examined DNA-calibrated divergence time estimates against the age of the amber deposits from which it came.• The fossil belongs to Elaphoglossum and is the first of a bolbitidoid fern. Its assignment to a particular section of Elaphoglossum could not be determined; however, sects. Lepidoglossa, Polytrichia, and Setosa can be discounted because the fossil lacks subulate scales or scales with acicular marginal hairs. Thus, the fossil might belong to either sects. Amygdalifolia, Wrightiana, Elaphoglossum, or Squamipedia or to an extinct lineage.• The discovery of a Miocene Elaphoglossum fossil provides remarkable support to current molecular clock-based estimates of the diversification of these ferns. © 2014 Botanical Society of America, Inc.

The influence of Pleistocene climatic changes and ocean currents on the phylogeography of the southern African barnacle, Tetraclita serrata (Thoracica; Cirripedia.

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Terry V Reynolds

Full Text Available The evolutionary effects of glacial periods are poorly understood for Southern Hemisphere marine intertidal species, particularly obligatory sessile organisms. We examined this by assessing the phylogeographic patterns of the southern African volcano barnacle, Tetraclita serrata, a dominant species on rocky intertidal shores. Restricted gene flow in some geographical areas was hypothesized based on oceanic circulation patterns and known biogeographic regions. Barnacle population genetic structure was investigated using the mitochondrial cytochrome oxidase subunit 1 (COI region for 410 individuals sampled from 20 localities spanning the South African coast. The mtDNA data were augmented by generating nuclear internal transcribed spacer 1 (ITS1 sequences from a subset of samples. Phylogenetic and population genetic analyses of mitochondrial DNA data reveal two distinct clades with mostly sympatric distributions, whereas nuclear analyses reveal only a single lineage. Shallow, but significant structure (0.0041-0.0065, P<0.01 was detected for the mtDNA data set, with the south-west African region identified as harbouring the highest levels of genetic diversity. Gene flow analyses on the mtDNA data show that individuals sampled in south-western localities experience gene flow primarily in the direction of the Benguela Current, while south and eastern localities experience bi-directional gene flow, suggesting an influence of both the inshore currents and the offshore Agulhas Current in the larval distribution of T. serrata. The mtDNA haplotype network, Bayesian Skyline Plots, mismatch distributions and time since expansion indicate that T. serrata population numbers were not severely affected by the Last Glacial Maximum (LGM, unlike other southern African marine species. The processes resulting in the two morphologically cryptic mtDNA lineages may be the result of a recent historical allopatric event followed by secondary contact or could reflect

Introducing the Algerian mitochondrial DNA and Y-chromosome profiles into the North African landscape.

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Asmahan Bekada

Full Text Available North Africa is considered a distinct geographic and ethnic entity within Africa. Although modern humans originated in this Continent, studies of mitochondrial DNA (mtDNA and Y-chromosome genealogical markers provide evidence that the North African gene pool has been shaped by the back-migration of several Eurasian lineages in Paleolithic and Neolithic times. More recent influences from sub-Saharan Africa and Mediterranean Europe are also evident. The presence of East-West and North-South haplogroup frequency gradients strongly reinforces the genetic complexity of this region. However, this genetic scenario is beset with a notable gap, which is the lack of consistent information for Algeria, the largest country in the Maghreb. To fill this gap, we analyzed a sample of 240 unrelated subjects from a northwest Algeria cosmopolitan population using mtDNA sequences and Y-chromosome biallelic polymorphisms, focusing on the fine dissection of haplogroups E and R, which are the most prevalent in North Africa and Europe respectively. The Eurasian component in Algeria reached 80% for mtDNA and 90% for Y-chromosome. However, within them, the North African genetic component for mtDNA (U6 and M1; 20% is significantly smaller than the paternal (E-M81 and E-V65; 70%. The unexpected presence of the European-derived Y-chromosome lineages R-M412, R-S116, R-U152 and R-M529 in Algeria and the rest of the Maghreb could be the counterparts of the mtDNA H1, H3 and V subgroups, pointing to direct maritime contacts between the European and North African sides of the western Mediterranean. Female influx of sub-Saharan Africans into Algeria (20% is also significantly greater than the male (10%. In spite of these sexual asymmetries, the Algerian uniparental profiles faithfully correlate between each other and with the geography.

A new phylogeographic pattern of endemic Bufo bankorensis in Taiwan Island is attributed to the genetic variation of populations.

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Teng-Lang Yu

Full Text Available To comprehend the phylogeographic patterns of genetic variation in anurans at Taiwan Island, this study attempted to examine (1 the existence of various geological barriers (Central Mountain Ranges, CMRs; and (2 the genetic variation of Bufo bankorensis using mtDNA sequences among populations located in different regions of Taiwan, characterized by different climates and existing under extreme conditions when compared available sequences of related species B. gargarizans of mainland China.Phylogenetic analyses of the dataset with mitochondrial DNA (mtDNA D-loop gene (348 bp recovered a close relationship between B. bankorensis and B. gargarizans, identified three distinct lineages. Furthermore, the network of mtDNA D-loop gene (564 bp amplified (279 individuals, 27 localities from Taiwan Island indicated three divergent clades within B. bankorensis (Clade W, E and S, corresponding to the geography, thereby verifying the importance of the CMRs and Kaoping River drainage as major biogeographic barriers. Mismatch distribution analysis, neutrality tests and Bayesian skyline plots revealed that a significant population expansion occurred for the total population and Clade W, with horizons dated to approximately 0.08 and 0.07 Mya, respectively. These results suggest that the population expansion of Taiwan Island species B. bankorensis might have resulted from the release of available habitat in post-glacial periods, the genetic variation on mtDNA showing habitat selection, subsequent population dispersal, and co-distribution among clades.The multiple origins (different clades of B. bankorensis mtDNA sequences were first evident in this study. The divergent genetic clades found within B. bankorensis could be independent colonization by previously diverged lineages; inferring B. bankorensis originated from B. gargarizans of mainland China, then dispersal followed by isolation within Taiwan Island. Highly divergent clades between W and E of B

Circulating mitochondrial DNA as biomarker linking environmental chemical exposure to early preclinical lesions elevation of mtDNA in human serum after exposure to carcinogenic halo-alkane-based pesticides.

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Lygia T Budnik

Full Text Available There is a need for a panel of suitable biomarkers for detection of environmental chemical exposure leading to the initiation or progression of degenerative diseases or potentially, to cancer. As the peripheral blood may contain increased levels of circulating cell-free DNA in diseased individuals, we aimed to evaluate this DNA as effect biomarker recognizing vulnerability after exposure to environmental chemicals. We recruited 164 individuals presumably exposed to halo-alkane-based pesticides. Exposure evaluation was based on human biomonitoring analysis; as biomarker of exposure parent halo-methanes, -ethanes and their metabolites, as well as the hemoglobin-adducts methyl valine and hydroxyl ethyl valine in blood were used, complemented by expert evaluation of exposure and clinical intoxication symptoms as well as a questionnaire. Assessment showed exposures to halo alkanes in the concentration range being higher than non-cancer reference doses (RfD but (mostly lower than the occupational exposure limits. We quantified circulating DNA in serum from 86 individuals with confirmed exposure to off-gassing halo-alkane pesticides (in storage facilities or in home environment and 30 non-exposed controls, and found that exposure was significantly associated with elevated serum levels of circulating mitochondrial DNA (in size of 79 bp, mtDNA-79, p = 0.0001. The decreased integrity of mtDNA (mtDNA-230/mtDNA-79 in exposed individuals implicates apoptotic processes (p = 0.015. The relative amounts of mtDNA-79 in serum were positively associated with the lag-time after intoxication to these chemicals (r = 0.99, p<0.0001. Several months of post-exposure the specificity of this biomarker increased from 30% to 97% in patients with intoxication symptoms. Our findings indicate that mitochondrial DNA has a potential to serve as a biomarker recognizing vulnerable risk groups after exposure to toxic/carcinogenic chemicals.

Highly variable rates of genome rearrangements between hemiascomycetous yeast lineages.

Directory of Open Access Journals (Sweden)

2006-03-01

Full Text Available Hemiascomycete yeasts cover an evolutionary span comparable to that of the entire phylum of chordates. Since this group currently contains the largest number of complete genome sequences it presents unique opportunities to understand the evolution of genome organization in eukaryotes. We inferred rates of genome instability on all branches of a phylogenetic tree for 11 species and calculated species-specific rates of genome rearrangements. We characterized all inversion events that occurred within synteny blocks between six representatives of the different lineages. We show that the rates of macro- and microrearrangements of gene order are correlated within individual lineages but are highly variable across different lineages. The most unstable genomes correspond to the pathogenic yeasts Candida albicans and Candida glabrata. Chromosomal maps have been intensively shuffled by numerous interchromosomal rearrangements, even between species that have retained a very high physical fraction of their genomes within small synteny blocks. Despite this intensive reshuffling of gene positions, essential genes, which cluster in low recombination regions in the genome of Saccharomyces cerevisiae, tend to remain syntenic during evolution. This work reveals that the high plasticity of eukaryotic genomes results from rearrangement rates that vary between lineages but also at different evolutionary times of a given lineage.

Broad phylogenomic sampling and the sister lineage of land plants.

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Ruth E Timme

Full Text Available The tremendous diversity of land plants all descended from a single charophyte green alga that colonized the land somewhere between 430 and 470 million years ago. Six orders of charophyte green algae, in addition to embryophytes, comprise the Streptophyta s.l. Previous studies have focused on reconstructing the phylogeny of organisms tied to this key colonization event, but wildly conflicting results have sparked a contentious debate over which lineage gave rise to land plants. The dominant view has been that 'stoneworts,' or Charales, are the sister lineage, but an alternative hypothesis supports the Zygnematales (often referred to as "pond scum" as the sister lineage. In this paper, we provide a well-supported, 160-nuclear-gene phylogenomic analysis supporting the Zygnematales as the closest living relative to land plants. Our study makes two key contributions to the field: 1 the use of an unbiased method to collect a large set of orthologs from deeply diverging species and 2 the use of these data in determining the sister lineage to land plants. We anticipate this updated phylogeny not only will hugely impact lesson plans in introductory biology courses, but also will provide a solid phylogenetic tree for future green-lineage research, whether it be related to plants or green algae.

Associations of mitochondrial haplogroups and mitochondrial DNA copy numbers with end-stage renal disease in a Han population.

Science.gov (United States)

Zhang, Yuheng; Zhao, Ying; Wen, Shuzhen; Yan, Rengna; Yang, Qinglan; Chen, Huimei

2017-09-01

Mitochondrial DNA (mtDNA) is closely related to mitochondrion function, and variations have been suggested to be involved in pathogenesis of complex diseases. The present study sought to elucidate mitochondrial haplogroups and mtDNA copy number in end-stage renal disease (ESRD) in a Han population. First, the mitochondrial haplogroups of 37 ESRD patients were clustered into several haplogroups, and haplogroup A & D were taken as the candidate risk haplogroups for ESRD. Second, the frequencies of A and D were assessed in 344 ESRD patients and 438 healthy controls, respectively. Haplogroup D was found to be risk maker for ESRD in young subjects (numbers were evaluated with quantitative-PCR. The ESRD patients exhibited greater cell-free mtDNA contents than the healthy controls but less intracellular mtDNA. Haplogroup D exhibited a further increase in cell-free mtDNA content and a decrease in intracellular mtDNA content among the ESRDs patients. Our findings suggest that mtNDA haplogroup D may contributes to pathogenesis of early-onset ESRD through alterations of mtDNA copy numbers.

Regal phylogeography: Range-wide survey of the marine angelfish Pygoplites diacanthus reveals evolutionary partitions between the Red Sea, Indian Ocean, and Pacific Ocean

KAUST Repository

Coleman, Richard R.

2016-04-08

The regal angelfish (Pygoplites diacanthus; family Pomacanthidae) occupies reefs from the Red Sea to the central Pacific, with an Indian Ocean/Rea Sea color morph distinct from a Pacific Ocean morph. To assess population differentiation and evaluate the possibility of cryptic evolutionary partitions in this monotypic genus, we surveyed mtDNA cytochrome b and two nuclear introns (S7 and RAG2) in 547 individuals from 15 locations. Phylogeographic analyses revealed four mtDNA lineages (d = 0.006 – 0.015) corresponding to the Pacific Ocean, the Red Sea, and two admixed lineages in the Indian Ocean, a pattern consistent with known biogeographical barriers. Christmas Island in the eastern Indian Ocean had both Indian and Pacific lineages. Both S7 and RAG2 showed strong population-level differentiation between the Red Sea, Indian Ocean, and Pacific Ocean (ΦST = 0.066 – 0.512). The only consistent population sub-structure within these three regions was at the Society Islands (French Polynesia), where surrounding oceanographic conditions may reinforce isolation. Coalescence analyses indicate the Pacific (1.7 Ma) as the oldest extant lineage followed by the Red Sea lineage (1.4 Ma). Results from a median-joining network suggest radiations of two lineages from the Red Sea that currently occupy the Indian Ocean (0.7 – 0.9 Ma). Persistence of a Red Sea lineage through Pleistocene glacial cycles suggests a long-term refuge in this region. The affiliation of Pacific and Red Sea populations, apparent in cytochrome b and S7 (but equivocal in RAG2) raises the hypthosis that the Indian Ocean was recolonized from the Red Sea, possibly more than once. Assessing the genetic architecture of this widespread monotypic genus reveals cryptic evolutionary diversity that merits subspecific recognition.

Regal phylogeography: Range-wide survey of the marine angelfish Pygoplites diacanthus reveals evolutionary partitions between the Red Sea, Indian Ocean, and Pacific Ocean

KAUST Repository

Coleman, Richard R.; Eble, Jeffrey A.; DiBattista, Joseph; Rocha, Luiz A.; Randall, John E.; Berumen, Michael L.; Bowen, Brian W.

2016-01-01

The regal angelfish (Pygoplites diacanthus; family Pomacanthidae) occupies reefs from the Red Sea to the central Pacific, with an Indian Ocean/Rea Sea color morph distinct from a Pacific Ocean morph. To assess population differentiation and evaluate the possibility of cryptic evolutionary partitions in this monotypic genus, we surveyed mtDNA cytochrome b and two nuclear introns (S7 and RAG2) in 547 individuals from 15 locations. Phylogeographic analyses revealed four mtDNA lineages (d = 0.006 – 0.015) corresponding to the Pacific Ocean, the Red Sea, and two admixed lineages in the Indian Ocean, a pattern consistent with known biogeographical barriers. Christmas Island in the eastern Indian Ocean had both Indian and Pacific lineages. Both S7 and RAG2 showed strong population-level differentiation between the Red Sea, Indian Ocean, and Pacific Ocean (ΦST = 0.066 – 0.512). The only consistent population sub-structure within these three regions was at the Society Islands (French Polynesia), where surrounding oceanographic conditions may reinforce isolation. Coalescence analyses indicate the Pacific (1.7 Ma) as the oldest extant lineage followed by the Red Sea lineage (1.4 Ma). Results from a median-joining network suggest radiations of two lineages from the Red Sea that currently occupy the Indian Ocean (0.7 – 0.9 Ma). Persistence of a Red Sea lineage through Pleistocene glacial cycles suggests a long-term refuge in this region. The affiliation of Pacific and Red Sea populations, apparent in cytochrome b and S7 (but equivocal in RAG2) raises the hypthosis that the Indian Ocean was recolonized from the Red Sea, possibly more than once. Assessing the genetic architecture of this widespread monotypic genus reveals cryptic evolutionary diversity that merits subspecific recognition.

Characterizing genetic diversity of contemporary pacific chickens using mitochondrial DNA analyses.

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Kelsey Needham Dancause

Full Text Available BACKGROUND: Mitochondrial DNA (mtDNA hypervariable region (HVR sequences of prehistoric Polynesian chicken samples reflect dispersal of two haplogroups--D and E--by the settlers of the Pacific. The distribution of these chicken haplogroups has been used as an indicator of human movement. Recent analyses suggested similarities between prehistoric Pacific and South American chicken samples, perhaps reflecting prehistoric Polynesian introduction of the chicken into South America. These analyses have been heavily debated. The current distribution of the D and E lineages among contemporary chicken populations in the Western Pacific is unclear, but might ultimately help to inform debates about the movements of humans that carried them. OBJECTIVES: We sought to characterize contemporary mtDNA diversity among chickens in two of the earliest settled archipelagos of Remote Oceania, the Marianas and Vanuatu. METHODS: We generated HVR sequences for 43 chickens from four islands in Vanuatu, and for 5 chickens from Guam in the Marianas. RESULTS: Forty samples from Vanuatu and three from Guam were assigned to haplogroup D, supporting this as a Pacific chicken haplogroup that persists in the Western Pacific. Two haplogroup E lineages were observed in Guam and two in Vanuatu. Of the E lineages in Vanuatu, one was identical to prehistoric Vanuatu and Polynesian samples and the other differed by one polymorphism. Contrary to our expectations, we observed few globally distributed domesticate lineages not associated with Pacific chicken dispersal. This might suggest less European introgression of chickens into Vanuatu than expected. If so, the E lineages might represent lineages maintained from ancient Pacific chicken introductions. The Vanuatu sample might thus provide an opportunity to distinguish between maintained ancestral Pacific chicken lineages and replacement by global domesticates through genomic analyses, which could resolve questions of contemporary

Mitochondrial DNA inheritance in the human fungal pathogen Cryptococcus gattii.

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Wang, Zixuan; Wilson, Amanda; Xu, Jianping

2015-02-01

The inheritance of mitochondrial DNA (mtDNA) is predominantly uniparental in most sexual eukaryotes. In this study, we examined the mitochondrial inheritance pattern of Cryptococcus gattii, a basidiomycetous yeast responsible for the recent and ongoing outbreak of cryptococcal infections in the US Pacific Northwest and British Columbia (especially Vancouver Island) in Canada. Using molecular markers, we analyzed the inheritance of mtDNA in 14 crosses between strains within and between divergent lineages in C. gattii. Consistent with results from recent studies, our analyses identified significant variations in mtDNA inheritance patterns among strains and crosses, ranging from strictly uniparental to biparental. For two of the crosses that showed uniparental mitochondrial inheritance in standard laboratory conditions, we further investigated the effects of the following environmental variables on mtDNA inheritance: UV exposure, temperature, and treatments with the methylation inhibitor 5-aza-2'-deoxycytidine and with the ubiquitination inhibitor ammonium chloride. Interestingly, one of these crosses showed no response to these environmental variables while the other exhibited diverse patterns ranging from complete uniparental inheritance of the MATa parent mtDNA, to biparental inheritance, and to a significant bias toward inheritance of the MATα parental mtDNA. Our results indicate that mtDNA inheritance in C. gattii differs from that in its closely related species Cryptococcus neoformans. Copyright © 2015 Elsevier Inc. All rights reserved.

Uniparental (mtDNA, Y-chromosome) polymorphisms in French Guiana and two related populations--implications for the region's colonization.

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Mazières, S; Guitard, E; Crubézy, E; Dugoujon, J-M; Bortolini, M C; Bonatto, S L; Hutz, M H; Bois, E; Tiouka, F; Larrouy, G; Salzano, F M

2008-01-01

Blood samples collected in four Amerindian French Guiana populations (Palikur, Emerillon, Wayampi and Kali'na) in the early 1980s were screened for selected mtDNA and Y-chromosome length polymorphisms, and sequenced for the mtDNA hypervariable segment I (HVS-I). In addition, two other Amerindian populations (Apalaí and Matsiguenga) were examined for the same markers to establish the genetic relationships in the area. Strong dissimilarities were observed in the distribution of the founding Amerindian haplogroups, and significant p-values were obtained from F(ST) genetic distances. Interpopulation similarities occurred mainly due to geography. The Palikur did not show obvious genetic similarity to the Matsiguenga, who speak the same language and live in a region from where they could have migrated to French Guiana. The African-origin admixture observed in the Kali'na probably derives from historical contacts they had with the Bushinengue (Noir Marron), a group of escaped slaves who now lead independent lives in a nearby region. This analysis has identified significant clues about the Amerindian peopling of the North-East Amazonian region.

Deciphering the recent phylogenetic expansion of the originally deeply rooted Mycobacterium tuberculosis lineage 7.

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Yimer, Solomon A; Namouchi, Amine; Zegeye, Ephrem Debebe; Holm-Hansen, Carol; Norheim, Gunnstein; Abebe, Markos; Aseffa, Abraham; Tønjum, Tone

2016-06-30

A deeply rooted phylogenetic lineage of Mycobacterium tuberculosis (M. tuberculosis) termed lineage 7 was discovered in Ethiopia. Whole genome sequencing of 30 lineage 7 strains from patients in Ethiopia was performed. Intra-lineage genome variation was defined and unique characteristics identified with a focus on genes involved in DNA repair, recombination and replication (3R genes). More than 800 mutations specific to M. tuberculosis lineage 7 strains were identified. The proportion of non-synonymous single nucleotide polymorphisms (nsSNPs) in 3R genes was higher after the recent expansion of M. tuberculosis lineage 7 strain started. The proportion of nsSNPs in genes involved in inorganic ion transport and metabolism was significantly higher before the expansion began. A total of 22346 bp deletions were observed. Lineage 7 strains also exhibited a high number of mutations in genes involved in carbohydrate transport and metabolism, transcription, energy production and conversion. We have identified unique genomic signatures of the lineage 7 strains. The high frequency of nsSNP in 3R genes after the phylogenetic expansion may have contributed to recent variability and adaptation. The abundance of mutations in genes involved in inorganic ion transport and metabolism before the expansion period may indicate an adaptive response of lineage 7 strains to enable survival, potentially under environmental stress exposure. As lineage 7 strains originally were phylogenetically deeply rooted, this may indicate fundamental adaptive genomic pathways affecting the fitness of M. tuberculosis as a species.

Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

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Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

2017-10-19

Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

High Yield of Adult Oligodendrocyte Lineage Cells Obtained from Meningeal Biopsy

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Sissi Dolci

2017-10-01

Full Text Available Oligodendrocyte loss can lead to cognitive and motor deficits. Current remyelinating therapeutic strategies imply either modulation of endogenous oligodendrocyte precursors or transplantation of in vitro expanded oligodendrocytes. Cell therapy, however, still lacks identification of an adequate source of oligodendrocyte present in adulthood and able to efficiently produce transplantable cells. Recently, a neural stem cell-like population has been identified in meninges. We developed a protocol to obtain high yield of oligodendrocyte lineage cells from one single biopsy of adult rat meningeal tissue. From 1 cm2 of adult rat spinal cord meninges, we efficiently expanded a homogenous culture of 10 millions of meningeal-derived oligodendrocyte lineage cells in a short period of time (approximately 4 weeks. Meningeal-derived oligodendrocyte lineage cells show typical mature oligodendrocyte morphology and express specific oligodendrocyte markers, such as galactosylceramidase and myelin basic protein. Moreover, when transplanted in a chemically demyelinated spinal cord model, meningeal-derived oligodendrocyte lineage cells display in vivo-remyelinating potential. This oligodendrocyte lineage cell population derives from an accessible and adult source, being therefore a promising candidate for autologous cell therapy of demyelinating diseases. In addition, the described method to differentiate meningeal-derived neural stem cells into oligodendrocyte lineage cells may represent a valid in vitro model to dissect oligodendrocyte differentiation and to screen for drugs capable to promote oligodendrocyte regeneration.

Imaging retinal progenitor lineages in developing zebrafish embryos.

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Jusuf, Patricia; Harris, William A; Poggi, Lucia

2013-03-01

In this protocol, we describe how to make and analyze four dimensional (4D) movies of retinal lineage in the zebrafish embryo in vivo. 4D consists of three spatial dimensions (3D) reconstructed from stacks of confocal planes plus one time dimension. Our imaging is performed on transgenic cells that express fluorescent proteins under the control of cell-specific promoters or on cells that transiently express such reporters in specific retinal cell progenitors. An important aspect of lineage tracing is the ability to follow individual cells as they undergo multiple cell divisions, final migration, and differentiation. This may mean many hours of 4D imaging, requiring that cells be kept healthy and maintained under conditions suitable for normal development. The longest movies we have made are ∼50 h. By analyzing these movies, we can see when a specific cell was born and who its sister was, allowing us to reconstruct its retinal lineages in vivo.

Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling

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Serafimidis, Ioannis; Rodriguez-Aznar, Eva; Lesche, Mathias; Yoshioka, Kazuaki; Takuwa, Yoh; Dahl, Andreas; Pan, Duojia; Gavalas, Anthony

2017-01-01

During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata, and genomics, we found that sphingosine-1-phosphate (S1p), signalling through the G protein coupled receptor (GPCR) S1pr2, plays a key role in pancreas development linking lineage allocation and specification. S1pr2 signalling promotes progenitor survival as well as acinar and endocrine specification. S1pr2-mediated stabilisation of the yes-associated protein (YAP) is essential for endocrine specification, thus linking a regulator of progenitor growth with specification. YAP stabilisation and endocrine cell specification rely on Gαi subunits, revealing an unexpected specificity of selected GPCR intracellular signalling components. Finally, we found that S1pr2 signalling posttranscriptionally attenuates Notch signalling levels, thus regulating lineage allocation. Both S1pr2-mediated YAP stabilisation and Notch attenuation are necessary for the specification of the endocrine lineage. These findings identify S1p signalling as a novel key pathway coordinating cell survival, lineage allocation, and specification and linking these processes by regulating YAP levels and Notch signalling. Understanding lineage allocation and specification in the pancreas will shed light in the origins of pancreatic diseases and may suggest novel therapeutic approaches. PMID:28248965

Two Hemocyte Lineages Exist in Silkworm Larval Hematopoietic Organ

OpenAIRE

Nakahara, Yuichi; Kanamori, Yasushi; Kiuchi, Makoto; Kamimura, Manabu

2010-01-01

BACKGROUND: Insects have multiple hemocyte morphotypes with different functions as do vertebrates, however, their hematopoietic lineages are largely unexplored with the exception of Drosophila melanogaster. METHODOLOGY/PRINCIPAL FINDINGS: To study the hematopoietic lineage of the silkworm, Bombyx mori, we investigated in vivo and in vitro differentiation of hemocyte precursors in the hematopoietic organ (HPO) into the four mature hemocyte subsets, namely, plasmatocytes, granulocytes, oenocyto...

Quantification of Crypt and Stem Cell Evolution in the Normal and Neoplastic Human Colon

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Ann-Marie Baker

2014-08-01

Full Text Available Human intestinal stem cell and crypt dynamics remain poorly characterized because transgenic lineage-tracing methods are impractical in humans. Here, we have circumvented this problem by quantitatively using somatic mtDNA mutations to trace clonal lineages. By analyzing clonal imprints on the walls of colonic crypts, we show that human intestinal stem cells conform to one-dimensional neutral drift dynamics with a “functional” stem cell number of five to six in both normal patients and individuals with familial adenomatous polyposis (germline APC−/+. Furthermore, we show that, in adenomatous crypts (APC−/−, there is a proportionate increase in both functional stem cell number and the loss/replacement rate. Finally, by analyzing fields of mtDNA mutant crypts, we show that a normal colon crypt divides around once every 30–40 years, and the division rate is increased in adenomas by at least an order of magnitude. These data provide in vivo quantification of human intestinal stem cell and crypt dynamics.

Eurasian otters, Lutra lutra, have a dominant mtDNA haplotype from the Iberian Peninsula to Scandinavia.

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Ferrando, Ainhoa; Ponsà, Montserrat; Marmi, Josep; Domingo-Roura, Xavier

2004-01-01

The Eurasian otter, Lutra lutra, has a Palaearctic distribution and has suffered a severe decline throughout Europe during the last century. Previous studies in this and other mustelids have shown reduced levels of variability in mitochondrial DNA, although otter phylogeographic studies were restricted to central-western Europe. In this work we have sequenced 361 bp of the mtDNA control region in 73 individuals from eight countries and added our results to eight sequences available from GenBank and the literature. The range of distribution has been expanded in relation to previous works north towards Scandinavia, east to Russia and Belarus, and south to the Iberian Peninsula. We found a single dominant haplotype in 91.78% of the samples, and six more haplotypes deviating a maximum of two mutations from the dominant haplotype restricted to a single country. Variability was extremely low in western Europe but higher in eastern countries. This, together with the lack of phylogeographical structuring, supports the postglacial recolonization of Europe from a single refugium. The Eurasian otter mtDNA control region has a 220-bp variable minisatellite in Domain III that we sequenced in 29 otters. We found a total of 19 minisatellite haplotypes, but they showed no phylogenetic information.

Y-chromosome evidence supports widespread signatures of three-species Canis hybridization in eastern North America.

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Wilson, Paul J; Rutledge, Linda Y; Wheeldon, Tyler J; Patterson, Brent R; White, Bradley N

2012-09-01

There has been considerable discussion on the origin of the red wolf and eastern wolf and their evolution independent of the gray wolf. We analyzed mitochondrial DNA (mtDNA) and a Y-chromosome intron sequence in combination with Y-chromosome microsatellites from wolves and coyotes within the range of extensive wolf-coyote hybridization, that is, eastern North America. The detection of divergent Y-chromosome haplotypes in the historic range of the eastern wolf is concordant with earlier mtDNA findings, and the absence of these haplotypes in western coyotes supports the existence of the North American evolved eastern wolf (Canis lycaon). Having haplotypes observed exclusively in eastern North America as a result of insufficient sampling in the historic range of the coyote or that these lineages subsequently went extinct in western geographies is unlikely given that eastern-specific mtDNA and Y-chromosome haplotypes represent lineages divergent from those observed in extant western coyotes. By combining Y-chromosome and mtDNA distributional patterns, we identified hybrid genomes of eastern wolf, coyote, gray wolf, and potentially dog origin in Canis populations of central and eastern North America. The natural contemporary eastern Canis populations represent an important example of widespread introgression resulting in hybrid genomes across the original C. lycaon range that appears to be facilitated by the eastern wolf acting as a conduit for hybridization. Applying conventional taxonomic nomenclature and species-based conservation initiatives, particularly in human-modified landscapes, may be counterproductive to the effective management of these hybrids and fails to consider their evolutionary potential.

Mitochondrial deoxyribonucleoside triphosphate pools in thymidine kinase 2 deficiency.

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Saada, Ann; Ben-Shalom, Efrat; Zyslin, Rivka; Miller, Chaya; Mandel, Hanna; Elpeleg, Orly

2003-10-24

Deficiency of mitochondrial thymidine kinase (TK2) is associated with mitochondrial DNA (mtDNA) depletion and manifests by severe skeletal myopathy in infancy. In order to elucidate the pathophysiology of this condition, mitochondrial deoxyribonucleoside triphosphate (dNTP) pools were determined in patients' fibroblasts. Despite normal mtDNA content and cytochrome c oxidase (COX) activity, mitochondrial dNTP pools were imbalanced. Specifically, deoxythymidine triphosphate (dTTP) content was markedly decreased, resulting in reduced dTTP:deoxycytidine triphosphate ratio. These findings underline the importance of balanced mitochondrial dNTP pools for mtDNA synthesis and may serve as the basis for future therapeutic interventions.

The role of H1 linker histone subtypes in preserving the fidelity of elaboration of mesendodermal and neuroectodermal lineages during embryonic development.

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Giang D Nguyen

Full Text Available H1 linker histone proteins are essential for the structural and functional integrity of chromatin and for the fidelity of additional epigenetic modifications. Deletion of H1c, H1d and H1e in mice leads to embryonic lethality by mid-gestation with a broad spectrum of developmental alterations. To elucidate the cellular and molecular mechanisms underlying H1 linker histone developmental functions, we analyzed embryonic stem cells (ESCs depleted of H1c, H1d and H1e subtypes (H1-KO ESCs by utilizing established ESC differentiation paradigms. Our study revealed that although H1-KO ESCs continued to express core pluripotency genes and the embryonic stem cell markers, alkaline phosphatase and SSEA1, they exhibited enhanced cell death during embryoid body formation and during specification of mesendoderm and neuroectoderm. In addition, we demonstrated deregulation in the developmental programs of cardiomyocyte, hepatic and pancreatic lineage elaboration. Moreover, ectopic neurogenesis and cardiomyogenesis occurred during endoderm-derived pancreatic but not hepatic differentiation. Furthermore, neural differentiation paradigms revealed selective impairments in the specification and maturation of glutamatergic and dopaminergic neurons with accelerated maturation of glial lineages. These impairments were associated with deregulation in the expression profiles of pro-neural genes in dorsal and ventral forebrain-derived neural stem cell species. Taken together, these experimental observations suggest that H1 linker histone proteins are critical for the specification, maturation and fidelity of organ-specific cellular lineages derived from the three cardinal germ layers.

Response pattern's of immunoglobulins evaluation in different lineages of mice infected with T. cruzi

International Nuclear Information System (INIS)

Silva, Andreia dos Santos

2006-01-01

The present work has employed different mice lineages (A/J, C57BL/6, B6AF1, BXA1 and BXA2) that were challenged with different doses of T. cruzi. The objective was to evaluate the pattern of immunoglobulins response presented by resistant and susceptible mice to T. cruzi as well as the lineages developed from the matting between them. So that evaluation was done by using lineages serums' sample, analyzed by ELISA's method. In agreement with the results observed all the lineages presented higher response to IgG2a and IgG2b, if compared with the titles to IgG1. IgG1 immunoglobulins involve a type Th2 pattern response which expressed allergic immunological responses, while IgG2 involves a pattern response Th1 that expresses cellular immunological response. The different lineages used in this research also presented different immunological response pattern by the infection with T. cruzi. Mice of the lineage C57BL/6 are resistant to the infection, while the animals of the lineage A/J are susceptible. The animals of the lineage B6AF1 are more resistant to the infection than their original parental C57BL/6. The immunological response developed by hybrid mice present traces of both susceptible and resistant parental A/J and C57BL/6, respectively. The animals of the lineage BXA1 can be considered resistant to the infection, but they don't present the same control as that presented by those of the lineages B6AF1 and C57BL/6. The animals of the lineage BXA2 can be considered susceptible to the infection, but they can control it for a long period, surviving like this, longer than the animals of the lineage A/J. In addition it was observed that the IgG2b immunoglobulins are very important to the resistance of mice to T. cruzi infection. (author)

Phylogeography of a Morphologically Cryptic Golden Mole Assemblage from South-Eastern Africa.

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Samantha Mynhardt

Full Text Available The Greater Maputaland-Pondoland-Albany (GMPA region of southern Africa was recently designated as a centre of vertebrate endemism. The phylogeography of the vertebrate taxa occupying this region may provide insights into the evolution of faunal endemism in south-eastern Africa. Here we investigate the phylogeographic patterns of an understudied small mammal species assemblage (Amblysomus endemic to the GMPA, to test for cryptic diversity within the genus, and to better understand diversification across the region. We sampled specimens from 50 sites across the distributional range of Amblysomus, with emphasis on the widespread A. hottentotus, to analyse geographic patterns of genetic diversity using mitochondrial DNA (mtDNA and nuclear intron data. Molecular dating was used to elucidate the evolutionary and phylogeographic history of Amblysomus. Our phylogenetic reconstructions show that A. hottentotus comprises several distinct lineages, or evolutionarily significant units (ESUs, some with restricted geographic ranges and thus worthy of conservation attention. Divergence of the major lineages dated to the early Pliocene, with later radiations in the GMPA during the late-Pliocene to early-Pleistocene. Evolutionary diversification within Amblysomus may have been driven by uplift of the Great Escarpment c. 5-3 million years ago (Ma, habitat changes associated with intensification of the east-west rainfall gradient across South Africa and the influence of subsequent global climatic cycles. These drivers possibly facilitated geographic spread of ancestral lineages, local adaptation and vicariant isolation. Our study adds to growing empirical evidence identifying East and southern Africa as cradles of vertebrate diversity.

Blind trials of computer-assisted structure elucidation software

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Moser Arvin

2012-02-01

Full Text Available Abstract Background One of the largest challenges in chemistry today remains that of efficiently mining through vast amounts of data in order to elucidate the chemical structure for an unknown compound. The elucidated candidate compound must be fully consistent with the data and any other competing candidates efficiently eliminated without doubt by using additional data if necessary. It has become increasingly necessary to incorporate an in silico structure generation and verification tool to facilitate this elucidation process. An effective structure elucidation software technology aims to mimic the skills of a human in interpreting the complex nature of spectral data while producing a solution within a reasonable amount of time. This type of software is known as computer-assisted structure elucidation or CASE software. A systematic trial of the ACD/Structure Elucidator CASE software was conducted over an extended period of time by analysing a set of single and double-blind trials submitted by a global audience of scientists. The purpose of the blind trials was to reduce subjective bias. Double-blind trials comprised of data where the candidate compound was unknown to both the submitting scientist and the analyst. The level of expertise of the submitting scientist ranged from novice to expert structure elucidation specialists with experience in pharmaceutical, industrial, government and academic environments. Results Beginning in 2003, and for the following nine years, the algorithms and software technology contained within ACD/Structure Elucidator have been tested against 112 data sets; many of these were unique challenges. Of these challenges 9% were double-blind trials. The results of eighteen of the single-blind trials were investigated in detail and included problems of a diverse nature with many of the specific challenges associated with algorithmic structure elucidation such as deficiency in protons, structure symmetry, a large number of

Engineered Murine HSCs Reconstitute Multi-lineage Hematopoiesis and Adaptive Immunity

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Yi-Fen Lu

2016-12-01

Full Text Available Hematopoietic stem cell (HSC transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients. Single-cell analysis shows that following engraftment in the bone marrow niche, these engineered HSCs further specify to a hybrid cell type, in which distinct gene regulatory networks of hematopoietic stem/progenitors and differentiated hematopoietic lineages are co-expressed. Our work demonstrates engineering of fully functional HSCs via modulation of genetic programs that govern self-renewal and lineage priming.

MtDNA COI-COII marker and drone congregation area: an efficient method to establish and monitor honeybee (Apis mellifera L.) conservation centres.

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Bertrand, Bénédicte; Alburaki, Mohamed; Legout, Hélène; Moulin, Sibyle; Mougel, Florence; Garnery, Lionel

2015-05-01

Honeybee subspecies have been affected by human activities in Europe over the past few decades. One such example is the importation of nonlocal subspecies of bees which has had an adverse impact on the geographical repartition and subsequently on the genetic diversity of the black honeybee Apis mellifera mellifera. To restore the original diversity of this local honeybee subspecies, different conservation centres were set up in Europe. In this study, we established a black honeybee conservation centre Conservatoire de l'Abeille Noire d'Ile de France (CANIF) in the region of Ile-de-France, France. CANIF's honeybee colonies were intensively studied over a 3-year period. This study included a drone congregation area (DCA) located in the conservation centre. MtDNA COI-COII marker was used to evaluate the genetic diversity of CANIF's honeybee populations and the drones found and collected from the DCA. The same marker (mtDNA) was used to estimate the interactions and the haplotype frequency between CANIF's honeybee populations and 10 surrounding honeybee apiaries located outside of the CANIF. Our results indicate that the colonies of the conservation centre and the drones of the DCA show similar stable profiles compared to the surrounding populations with lower level of introgression. The mtDNA marker used on both DCA and colonies of the conservation centre seems to be an efficient approach to monitor and maintain the genetic diversity of the protected honeybee populations. © 2014 John Wiley & Sons Ltd.

Lineage-Specific Expansion of the Chalcone Synthase Gene Family in Rosids.

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Kattina Zavala

Full Text Available Rosids are a monophyletic group that includes approximately 70,000 species in 140 families, and they are found in a variety of habitats and life forms. Many important crops such as fruit trees and legumes are rosids. The evolutionary success of this group may have been influenced by their ability to produce flavonoids, secondary metabolites that are synthetized through a branch of the phenylpropanoid pathway where chalcone synthase is a key enzyme. In this work, we studied the evolution of the chalcone synthase gene family in 12 species belonging to the rosid clade. Our results show that the last common ancestor of the rosid clade possessed six chalcone synthase gene lineages that were differentially retained during the evolutionary history of the group. In fact, of the six gene lineages that were present in the last common ancestor, 7 species retained 2 of them, whereas the other 5 only retained one gene lineage. We also show that one of the gene lineages was disproportionately expanded in species that belonged to the order Fabales (soybean, barrel medic and Lotus japonicas. Based on the available literature, we suggest that this gene lineage possesses stress-related biological functions (e.g., response to UV light, pathogen defense. We propose that the observed expansion of this clade was a result of a selective pressure to increase the amount of enzymes involved in the production of phenylpropanoid pathway-derived secondary metabolites, which is consistent with the hypothesis that suggested that lineage-specific expansions fuel plant adaptation.

Novel 12S mtDNA findings in sloths (Pilosa, Folivora and anteaters (Pilosa, Vermilingua suggest a true case of long branch attraction

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Maria Claudene Barros

2008-01-01

Full Text Available We sequenced 12S RNA mtDNA for the majority of the extant species of sloths and anteaters and compared our results with previous data obtained by our group using 16S RNA mtDNA in the same specimens and to GenBank sequences of the extinct giant sloth Mylodon. Our results suggest that pigmy-anteaters may be a case of the long-branch attraction phenomenon and also show the large genetic difference between the Amazonian and Atlantic forest three-toed sloths, contrasting with the small differences observed between the two non-Atlantic forest forms of sloths. These results have important implications for the taxonomy of sloths and anteaters and strongly suggest the placement of pigmy anteaters in their own family (Cyclopidae and raising the taxonomic status of Bradypus torquatus to a genus.

Spiralian phylogeny informs the evolution of microscopic lineages.

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Laumer, Christopher E; Bekkouche, Nicolas; Kerbl, Alexandra; Goetz, Freya; Neves, Ricardo C; Sørensen, Martin V; Kristensen, Reinhardt M; Hejnol, Andreas; Dunn, Casey W; Giribet, Gonzalo; Worsaae, Katrine

2015-08-03

Despite rapid advances in the study of metazoan evolutionary history [1], phylogenomic analyses have so far neglected a number of microscopic lineages that possess a unique combination of characters and are thus informative for our understanding of morphological evolution. Chief among these lineages are the recently described animal groups Micrognathozoa and Loricifera, as well as the two interstitial "Problematica" Diurodrilus and Lobatocerebrum [2]. These genera show a certain resemblance to Annelida in their cuticle and gut [3, 4]; however, both lack primary annelid characters such as segmentation and chaetae [5]. Moreover, they show unique features such as an inverted body-wall musculature or a novel pharyngeal organ. This and their ciliated epidermis have led some to propose relationships with other microscopic spiralians, namely Platyhelminthes, Gastrotricha, and in the case of Diurodrilus, with Micrognathozoa [6, 7]-lineages that are grouped by some analyses into "Platyzoa," a clade whose status remains uncertain [1, 8-11]. Here, we assess the interrelationships among the meiofaunal and macrofaunal members of Spiralia using 402 orthologs mined from genome and transcriptome assemblies of 90 taxa. Lobatocerebrum and Diurodrilus are found to be deeply nested members of Annelida, and unequivocal support is found for Micrognathozoa as the sister group of Rotifera. Analyses using site-heterogeneous substitution models further recover a lophophorate clade and position Loricifera + Priapulida as sister group to the remaining Ecdysozoa. Finally, with several meiofaunal lineages branching off early in the diversification of Spiralia, the emerging concept of a microscopic, acoelomate, direct-developing ancestor of Spiralia is reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human Kin Investment as a Function of Genetic Relatedness and Lineage

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Gregory D. Webster

2004-01-01

Full Text Available Two independent samples of students were asked to allocate fictional lotteries of varying dollar amounts to their blood relatives. In both studies, a reliable genetic relatedness by lineage interaction emerged, such that the genetic effect was a more positive predictor of percent of money allocated for relatives of a direct lineage (e.g., parents, grandparents than it was for peripheral relatives (e.g., siblings, aunts and uncles. In a third study, this interaction was replicated in an archival analysis of wills. The implications of accounting for differences in relatives' lineages in studies of kin investment are discussed.

Regional Variation in mtDNA of the Lesser Prairie-Chicken

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Hagen, Christian A.; Pitman, James C.; Sandercock, Brett K.; Wolfe, Don H.; Robel, Robel J.; Applegate, Roger D.; Oyler-McCance, Sara J.

2010-01-01

Cumulative loss of habitat and long-term decline in the populations of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) have led to concerns for the species' viability throughout its range in the southern Great Plains. For more efficient conservation past and present distributions of genetic variation need to be understood. We examined the distribution of mitochondrial DNA (mtDNA) variation in the Lesser Prairie-Chicken across Kansas, Colorado, Oklahoma, and New Mexico. Throughout the range we found little genetic differentiation except for the population in New Mexico, which was significantly different from most other publications. We did, however, find significant isolation by distance at the rangewide scale (r=0.698). We found no relationship between haplotype phylogeny and geography, and our analyses provide evidence for a post-glacial population expansion within the species that is consistent with the idea that speciation within Tympanuchus is recent. Conservation actions that increase the likelihood of genetically viable populations in the future should be evaluated for implementation.

CRX is a diagnostic marker of retinal and pineal lineage tumors.

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Sandro Santagata

2009-11-01

Full Text Available CRX is a homeobox transcription factor whose expression and function is critical to maintain retinal and pineal lineage cells and their progenitors. To determine the biologic and diagnostic potential of CRX in human tumors of the retina and pineal, we examined its expression in multiple settings.Using situ hybridization and immunohistochemistry we show that Crx RNA and protein expression are exquisitely lineage restricted to retinal and pineal cells during normal mouse and human development. Gene expression profiling analysis of a wide range of human cancers and cancer cell lines also supports that CRX RNA is highly lineage restricted in cancer. Immunohistochemical analysis of 22 retinoblastomas and 13 pineal parenchymal tumors demonstrated strong expression of CRX in over 95% of these tumors. Importantly, CRX was not detected in the majority of tumors considered in the differential diagnosis of pineal region tumors (n = 78. The notable exception was medulloblastoma, 40% of which exhibited CRX expression in a heterogeneous pattern readily distinguished from that seen in retino-pineal tumors.These findings describe new potential roles for CRX in human cancers and highlight the general utility of lineage restricted transcription factors in cancer biology. They also identify CRX as a sensitive and specific clinical marker and a potential lineage dependent therapeutic target in retinoblastoma and pineoblastoma.

TECHNOLOGICAL CHARACTERIZATION AND CLASSIFICATION OF WHEAT LINEAGES CULTIVATED IN THE CERRADO MINEIRO

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Raul Antônio Viana Madeira

2015-06-01

Full Text Available Farmers need highly productive wheat cultivars in order to reach better profitability. However, this alone is not enough, because, in order to serve the mills, the food industry, and more specifically, the bakers, wheat cultivars must present minimum quality requirements that result in final products of superior quality. This study was conducted with the goals of performing the technological characterization of wheat flour five lineages developed for cultivation in the Cerrado Mineiro; compare the flours of these lineages with the wheat flour of two commercial wheat cultivars, and classify the wheat lineages according to current Brazilian legislation. A completely randomized design was conducted with seven treatments and three replicates. Moisture, protein and ashes content, and the rheological characteristics of the flours were determined. The EP066066 lineage as rated was basic wheat. The EP066055, EP064021, EP062043 and EP063065 were rated as bread wheat. Among the studied lineages, the wheat flour from the EP062043 stood from the others, presenting considerable gluten contents, good level of mixing tolerance, good stability and good gluten strength.

60,000 years of interactions between Central and Eastern Africa documented by major African mitochondrial haplogroup L2.

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Silva, Marina; Alshamali, Farida; Silva, Paula; Carrilho, Carla; Mandlate, Flávio; Jesus Trovoada, Maria; Černý, Viktor; Pereira, Luísa; Soares, Pedro

2015-07-27

Mitochondrial DNA (mtDNA) haplogroup L2 originated in Western Africa but is nowadays spread across the entire continent. L2 movements were previously postulated to be related to the Bantu expansion, but L2 expansions eastwards probably occurred much earlier. By reconstructing the phylogeny of L2 (44 new complete sequences) we provide insights on the complex net of within-African migrations in the last 60 thousand years (ka). Results show that lineages in Southern Africa cluster with Western/Central African lineages at a recent time scale, whereas, eastern lineages seem to be substantially more ancient. Three moments of expansion from a Central African source are associated to L2: (1) one migration at 70-50 ka into Eastern or Southern Africa, (2) postglacial movements (15-10 ka) into Eastern Africa; and (3) the southward Bantu Expansion in the last 5 ka. The complementary population and L0a phylogeography analyses indicate no strong evidence of mtDNA gene flow between eastern and southern populations during the later movement, suggesting low admixture between Eastern African populations and the Bantu migrants. This implies that, at least in the early stages, the Bantu expansion was mainly a demic diffusion with little incorporation of local populations.

The Three Lineages of the Diploid Hybrid Verticillium longisporum Differ in Virulence and Pathogenicity.

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Novakazi, Fluturë; Inderbitzin, Patrik; Sandoya, German; Hayes, Ryan J; von Tiedemann, Andreas; Subbarao, Krishna V

2015-05-01

Verticillium longisporum is an economically important vascular pathogen of Brassicaceae crops in different parts of the world. V. longisporum is a diploid hybrid that consists of three different lineages, each of which originated from a separate hybridization event between two different sets of parental species. We used 20 isolates representing the three V. longisporum lineages and the relative V. dahliae, and performed pathogenicity tests on 11 different hosts, including artichoke, cabbage, cauliflower, cotton, eggplant, horseradish, lettuce, linseed, oilseed rape (canola), tomato, and watermelon. V. longisporum was overall more virulent on the Brassicaceae crops than V. dahliae, which was more virulent than V. longisporum across the non-Brassicaceae crops. There were differences in virulence between the three V. longisporum lineages. V. longisporum lineage A1/D1 was the most virulent lineage on oilseed rape, and V. longisporum lineage A1/D2 was the most virulent lineage on cabbage and horseradish. We also found that on the non-Brassicaceae hosts eggplant, tomato, lettuce, and watermelon, V. longisporum was more or equally virulent than V. dahliae. This suggests that V. longisporum may have a wider potential host range than currently appreciated.

Variation and association to diabetes in 2000 full mtDNA sequences mined from an exome study in a Danish population

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Li, Shengting; Besenbacher, Soren; Li, Yingrui

2014-01-01

In this paper, we mine full mtDNA sequences from an exome capture data set of 2000 Danes, showing that it is possible to get high-quality full-genome sequences of the mitochondrion from this resource. The sample includes 1000 individuals with type 2 diabetes and 1000 controls. We characterise...

Expanding the Entamoeba Universe: New Hosts Yield Novel Ribosomal Lineages.

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Jacob, Alison S; Busby, Eloise J; Levy, Abigail D; Komm, Natasha; Clark, C Graham

2016-01-01

Removing the requirement for cell culture has led to a substantial increase in the number of lineages of Entamoeba recognized as distinct. Surveying the range of potential host species for this parasite genus has barely been started and it is clear that additional sampling of the same host in different locations often identifies additional diversity. In this study, using small subunit ribosomal RNA gene sequencing, we identify four new lineages of Entamoeba, including the first report of Entamoeba from an elephant, and extend the host range of some previously described lineages. In addition, examination of microbiome data from a number of host animals suggests that substantial Entamoeba diversity remains to be uncovered. © 2015 The Author(s) Journal of Eukaryotic Microbiology © 2015 International Society of Protistologists.

Mitochondrial DNA structure in the Arabian Peninsula

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Cabrera Vicente M

2008-02-01

Full Text Available Abstract Background Two potential migratory routes followed by modern humans to colonize Eurasia from Africa have been proposed. These are the two natural passageways that connect both continents: the northern route through the Sinai Peninsula and the southern route across the Bab al Mandab strait. Recent archaeological and genetic evidence have favored a unique southern coastal route. Under this scenario, the study of the population genetic structure of the Arabian Peninsula, the first step out of Africa, to search for primary genetic links between Africa and Eurasia, is crucial. The haploid and maternally inherited mitochondrial DNA (mtDNA molecule has been the most used genetic marker to identify and to relate lineages with clear geographic origins, as the African Ls and the Eurasian M and N that have a common root with the Africans L3. Results To assess the role of the Arabian Peninsula in the southern route, we genetically analyzed 553 Saudi Arabs using partial (546 and complete mtDNA (7 sequencing, and compared the lineages obtained with those present in Africa, the Near East, central, east and southeast Asia and Australasia. The results showed that the Arabian Peninsula has received substantial gene flow from Africa (20%, detected by the presence of L, M1 and U6 lineages; that an 18% of the Arabian Peninsula lineages have a clear eastern provenance, mainly represented by U lineages; but also by Indian M lineages and rare M links with Central Asia, Indonesia and even Australia. However, the bulk (62% of the Arabian lineages has a Northern source. Conclusion Although there is evidence of Neolithic and more recent expansions in the Arabian Peninsula, mainly detected by (preHV1 and J1b lineages, the lack of primitive autochthonous M and N sequences, suggests that this area has been more a receptor of human migrations, including historic ones, from Africa, India, Indonesia and even Australia, than a demographic expansion center along the

A 28,000 Years Old Cro-Magnon mtDNA Sequence Differs from All Potentially Contaminating Modern Sequences

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Caramelli, David; Milani, Lucio; Vai, Stefania; Modi, Alessandra; Pecchioli, Elena; Girardi, Matteo; Pilli, Elena; Lari, Martina; Lippi, Barbara; Ronchitelli, Annamaria; Mallegni, Francesco; Casoli, Antonella; Bertorelle, Giorgio; Barbujani, Guido

2008-01-01

Background DNA sequences from ancient speciments may in fact result from undetected contamination of the ancient specimens by modern DNA, and the problem is particularly challenging in studies of human fossils. Doubts on the authenticity of the available sequences have so far hampered genetic comparisons between anatomically archaic (Neandertal) and early modern (Cro-Magnoid) Europeans. Methodology/Principal Findings We typed the mitochondrial DNA (mtDNA) hypervariable region I in a 28,000 years old Cro-Magnoid individual from the Paglicci cave, in Italy (Paglicci 23) and in all the people who had contact with the sample since its discovery in 2003. The Paglicci 23 sequence, determined through the analysis of 152 clones, is the Cambridge reference sequence, and cannot possibly reflect contamination because it differs from all potentially contaminating modern sequences. Conclusions/Significance: The Paglicci 23 individual carried a mtDNA sequence that is still common in Europe, and which radically differs from those of the almost contemporary Neandertals, demonstrating a genealogical continuity across 28,000 years, from Cro-Magnoid to modern Europeans. Because all potential sources of modern DNA contamination are known, the Paglicci 23 sample will offer a unique opportunity to get insight for the first time into the nuclear genes of early modern Europeans. PMID:18628960

A 28,000 years old Cro-Magnon mtDNA sequence differs from all potentially contaminating modern sequences.

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David Caramelli

Full Text Available BACKGROUND: DNA sequences from ancient specimens may in fact result from undetected contamination of the ancient specimens by modern DNA, and the problem is particularly challenging in studies of human fossils. Doubts on the authenticity of the available sequences have so far hampered genetic comparisons between anatomically archaic (Neandertal and early modern (Cro-Magnoid Europeans. METHODOLOGY/PRINCIPAL FINDINGS: We typed the mitochondrial DNA (mtDNA hypervariable region I in a 28,000 years old Cro-Magnoid individual from the Paglicci cave, in Italy (Paglicci 23 and in all the people who had contact with the sample since its discovery in 2003. The Paglicci 23 sequence, determined through the analysis of 152 clones, is the Cambridge reference sequence, and cannot possibly reflect contamination because it differs from all potentially contaminating modern sequences. CONCLUSIONS/SIGNIFICANCE: The Paglicci 23 individual carried a mtDNA sequence that is still common in Europe, and which radically differs from those of the almost contemporary Neandertals, demonstrating a genealogical continuity across 28,000 years, from Cro-Magnoid to modern Europeans. Because all potential sources of modern DNA contamination are known, the Paglicci 23 sample will offer a unique opportunity to get insight for the first time into the nuclear genes of early modern Europeans.

T-lineage blast crisis of chronic myelogenous leukemia: simple record of 4 cases

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Kartika W. Taroeno-Hariadi

2005-09-01

Full Text Available Blast crisis (BC transformation in chronic myelogenous leukemia (CML can involve each differentiation lineage of the hematopoietic system, i.e. granulocyte, monocyte, erythrocyte, megakaryocyte, and lymphocyte lineage. The lymphoid blast crisis (BC leukemia cells usually belong to B-lineage, commonly having the phenotype of Pre-B stage of the B-lineage, in which cell-surface immunoglobulin (sIg is not yet expressed. In contrast, T-lineage BC of CML is extremely rare. The objective of this study is to describe the fenotype, fusion transcript of bcr-abl, TdT, and cytoplasmic CD3 in T-lineage BC CML cases. Case report study. This report shows a simple summary of 4 cases of T-lineage BC of CML which have been collected in the phenotypic and genotypic analysis study for 17 years (1987-2004. In all cases, the chromosomal analysis revealed the presence of t(9;22(q34;q11 at presentation. Cell surface analysis were done at diagnosis. Cases’ mononuclear cells stored as 10% DMSO were retrieved to be performed reverse transcription (RT PCR BCR-ABL multiplex to demonstrate the presence of the fusion transcript of bcr-abl. RT-PCR was also performed for detecting the expression of cytoplasmic CD3ε and terminal deoxynucleotydil transferase (TdT. The results of cell surface antigen (CSA at presentation showed that 1 case was CD7+, CD5-, and CD2-; 1 case CD7+, CD5+, and CD2-; and 2 cases CD7+, CD5+ and CD2+ indicating that all these T-lineage BC of CML cells show the phenotype of pre-(pro- thymic stage phenotype. In the present study, two cases showed b2a2, one e1a2, and one negative bcr-abl transcript. The RT-PCR revealed the presence of CD3ε mRNA in all cases, and TdT mRNA in only one case. These results can constitute a basis for the future analysis of T-lineage BC of CML from now on. (Med J Indones 2005; 14: 184-9Keywords: chronic myelogenous leukemia (CML, blastic crisis (BC, T-lineage, bcr-abl fusion gene, CDε, TdT

Evolution of two distinct phylogenetic lineages of the emerging human pathogen Mycobacterium ulcerans

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Portaels Francoise

2007-09-01

Full Text Available Abstract Background Comparative genomics has greatly improved our understanding of the evolution of pathogenic mycobacteria such as Mycobacterium tuberculosis. Here we have used data from a genome microarray analysis to explore insertion-deletion (InDel polymorphism among a diverse strain collection of Mycobacterium ulcerans, the causative agent of the devastating skin disease, Buruli ulcer. Detailed analysis of large sequence polymorphisms in twelve regions of difference (RDs, comprising irreversible genetic markers, enabled us to refine the phylogenetic succession within M. ulcerans, to define features of a hypothetical M. ulcerans most recent common ancestor and to confirm its origin from Mycobacterium marinum. Results M. ulcerans has evolved into five InDel haplotypes that separate into two distinct lineages: (i the "classical" lineage including the most pathogenic genotypes – those that come from Africa, Australia and South East Asia; and (ii an "ancestral" M. ulcerans lineage comprising strains from Asia (China/Japan, South America and Mexico. The ancestral lineage is genetically closer to the progenitor M. marinum in both RD composition and DNA sequence identity, whereas the classical lineage has undergone major genomic rearrangements. Conclusion Results of the InDel analysis are in complete accord with recent multi-locus sequence analysis and indicate that M. ulcerans has passed through at least two major evolutionary bottlenecks since divergence from M. marinum. The classical lineage shows more pronounced reductive evolution than the ancestral lineage, suggesting that there may be differences in the ecology between the two lineages. These findings improve the understanding of the adaptive evolution and virulence of M. ulcerans and pathogenic mycobacteria in general and will facilitate the development of new tools for improved diagnostics and molecular epidemiology.

Evidence of two distinct phylogenetic lineages of dog rabies virus circulating in Cambodia.

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Mey, Channa; Metlin, Artem; Duong, Veasna; Ong, Sivuth; In, Sotheary; Horwood, Paul F; Reynes, Jean-Marc; Bourhy, Hervé; Tarantola, Arnaud; Buchy, Philippe

2016-03-01

This first extensive retrospective study of the molecular epidemiology of dog rabies in Cambodia included 149 rabies virus (RABV) entire nucleoprotein sequences obtained from 1998-2011. The sequences were analyzed in conjunction with RABVs from other Asian countries. Phylogenetic reconstruction confirmed the South-East Asian phylogenetic clade comprising viruses from Cambodia, Vietnam, Thailand, Laos and Myanmar. The present study represents the first attempt to classify the phylogenetic lineages inside this clade, resulting in the confirmation that all the Cambodian viruses belonged to the South-East Asian (SEA) clade. Three distinct phylogenetic lineages in the region were established with the majority of viruses from Cambodia closely related to viruses from Thailand, Laos and Vietnam, forming the geographically widespread phylogenetic lineage SEA1. A South-East Asian lineage SEA2 comprised two viruses from Cambodia was identified, which shared a common ancestor with RABVs originating from Laos. Viruses from Myanmar formed separate phylogenetic lineages within the major SEA clade. Bayesian molecular clock analysis suggested that the time to most recent common ancestor (TMRCA) of all Cambodian RABVs dated to around 1950. The TMRCA of the Cambodian SEA1 lineage was around 1964 and that of the SEA2 lineage was around 1953. The results identified three phylogenetically distinct and geographically separated lineages inside the earlier identified major SEA clade, covering at least five countries in the region. A greater understanding of the molecular epidemiology of rabies in South-East Asia is an important step to monitor progress on the efforts to control canine rabies in the region. Copyright © 2015 Elsevier B.V. All rights reserved.

Spatiotemporal dynamics of DENV-2 Asian-American genotype lineages in the Americas.

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Daiana Mir

Full Text Available The Asian/American (AS/AM genotype of dengue virus type 2 (DENV-2 has been evolving in the Americas over the last 30 years, leading to several waves of dengue epidemics and to the emergence of different viral lineages in the region. In this study, we investigate the spatiotemporal dissemination pattern of the DENV-2 lineages at a regional level. We applied phylogenetic and phylogeographic analytical methods to a comprehensive data set of 582 DENV-2 E gene sequences of the AS/AM genotype isolated from 29 different American countries over a period of 30 years (1983 to 2012. Our study reveals that genetic diversity of DENV-2 AS/AM genotype circulating in the Americas mainly resulted from one single founder event and can be organized in at least four major lineages (I to IV, which emerged in the Caribbean region at the early 1980s and then spread and die out with different dynamics. Lineages I and II dominate the epidemics in the Caribbean region during the 1980s and early 1990 s, lineage III becomes the prevalent DENV-2 one in the Caribbean and South America during the 1990 s, whereas lineage IV dominates the epidemics in South and Central America during the 2000s. Suriname and Guyana seem to represent important entry points for DENV-2 from the Lesser Antilles to South America, whereas Venezuela, Brazil and Nicaragua were pointed as the main secondary hubs of dissemination to other mainland countries. Our study also indicates that DENV-2 AS/AM genotype was disseminated within South America following two main routes. The first route hits Venezuela and the western side of the Andes, while the second route mainly hits Brazil and the eastern side of the Andes. The phenomenon of DENV-2 lineage replacement across successive epidemic outbreaks was a common characteristic in all American countries, although the timing of lineage replacements greatly vary across locations.

Genetic analysis of maternal and paternal lineages in Kabardian horses by uniparental molecular markers

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Aliy-bek D. Khaudov

2018-02-01

Full Text Available Studies of mitochondrial DNA (mtDNA as well as the non-recombining part of the Y chromosome help to understand the origin and distribution of maternal and paternal lineages. The Kabardian horse from Northern Caucasia which is well-known for strength, stamina and endurance in distance riding has a large gap in its breeding documentation especially in the recent past. A 309 bp fragment of the mitochondrial D-loop (156 Kabardian horses and six mutations in Y chromosome (49 Kabardian stallions, respectively, were analyzed to get a better insight into breeding history, phylogenetic relationship to related breeds, maternal and paternal diversity and genetic structure. We found a high mitochondrial diversity represented by 64 D-loop haplotypes out of 14 haplogroups. The most frequent haplogroups were G (19.5%, L (12.3%, Q (11.7%, and B (11.0%. Although these four haplogroups are also frequently found in Asian riding horses (e.g. Buryat, Kirghiz, Mongolian, Transbaikalian, Tuvinian the percentage of the particular haplogroups varies sometimes remarkable. In contrast, the obtained haplogroup pattern from Kabardian horse was more similar to that of breeds reared in the Middle East. No specific haplotype cluster was observed in the phylogenetic tree for Kabardian horses. On Kabardian Y chromosome, two mutations were found leading to three haplotypes with a percentage of 36.7% (haplotype HT1, 38.8% (haplotype HT2 and 24.5% (haplotype HT3, respectively. The high mitochondrial and also remarkable paternal diversity of the Kabardian horse is caused by its long history with a widely spread maternal origin and the introduction of Arabian as well as Thoroughbred influenced stallions for improvement. This high genetic diversity provides a good situation for the ongoing breed development and performance selection as well as avoiding inbreeding.

Population Structure of mtDNA Variation due to Pleistocene Fluctuations in the South American Maned Wolf (Chrysocyon brachyurus, Illiger, 1815): Management Units for Conservation.

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González, Susana; Cosse, Mariana; Franco, María del Rosario; Emmons, Louise; Vynne, Carly; Duarte, José Maurício Barbanti; Beccacesi, Marcelo D; Maldonado, Jesús E

2015-01-01

The maned wolf (Chrysocyon brachyurus) is one of the largest South American canids, and conservation across this charismatic carnivore's large range is presently hampered by a lack of knowledge about possible natural subdivisions which could influence the population's viability. To elucidate the phylogeographic patterns and demographic history of the species, we used 2 mtDNA markers (D-loop and cytochrome b) from 87 individuals collected throughout their range, in Argentina, Bolivia, Brazil, and Uruguay. We found moderate levels of haplotype and nucleotide diversity, and the 14 D-loop haplotypes were closely related. Genetic structure results revealed 4 groups, and when coupled with model inferences from a coalescent analysis, suggested that maned wolves have undergone demographic fluctuations due to changes in climate and habitat during the Pleistocene glaciation period approximately 24000 years before present (YBP). This genetic signature points to an event that occurred within the timing estimated for the start of the contraction of the Cerrado around 50000 YBP. Our results reveal a genetic signature of population size expansion followed by contraction during Pleistocene interglaciations, which had similar impacts on other South American mammals. The 4 groups should for now be considered management units, within which future monitoring efforts should be conducted independently. © The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Polycomb enables primitive endoderm lineage priming in embryonic stem cells

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Illingworth, Robert S; Hölzenspies, Jurriaan J; Roske, Fabian V

2016-01-01

Mouse embryonic stem cells (ESCs), like the blastocyst from which they are derived, contain precursors of the epiblast (Epi) and primitive endoderm (PrEn) lineages. While transient in vivo, these precursor populations readily interconvert in vitro. We show that altered transcription is the driver...... polycomb with dynamic changes in transcription and stalled lineage commitment, allowing cells to explore alternative choices prior to a definitive decision....

Little Divergence Among Mitochondrial Lineages of Prochilodus (Teleostei, Characiformes

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Bruno F. Melo

2018-04-01

Full Text Available Evidence that migration prevents population structure among Neotropical characiform fishes has been reported recently but the effects upon species diversification remain unclear. Migratory species of Prochilodus have complex species boundaries and intrincate taxonomy representing a good model to address such questions. Here, we analyzed 147 specimens through barcode sequences covering all species of Prochilodus across a broad geographic area of South America. Species delimitation and population genetic methods revealed very little genetic divergence among mitochondrial lineages suggesting that extensive gene flow resulted likely from the highly migratory behavior, natural hybridization or recent radiation prevent accumulation of genetic disparity among lineages. Our results clearly delimit eight genetic lineages in which four of them contain a single species and four contain more than one morphologically problematic taxon including a trans-Andean species pair and species of the P. nigricans group. Information about biogeographic distribution of haplotypes presented here might contribute to further research on the population genetics and taxonomy of Prochilodus.

Mitochondrial DNA copy number in peripheral blood cell and hypertension risk among mining workers: a case-control study in Chinese coal miners.

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Lei, L; Guo, J; Shi, X; Zhang, G; Kang, H; Sun, C; Huang, J; Wang, T

2017-09-01

Alteration of mitochondrial DNA (mtDNA) copy number, which reflects oxidant-induced cell damage, has been observed in a wide range of human diseases. However, whether it correlates with hypertension has not been elucidated. We aimed to explore the association between mtDNA copy number and the risk of hypertension in Chinese coal miners. A case-control study was performed with 378 hypertension patients and 325 healthy controls in a large coal mining group located in North China. Face-to-face interviews were conducted by trained staffs with necessary medical knowledge. The mtDNA copy number was measured by a quantitative real-time PCR assay using DNA extracted from peripheral blood. No significant differences in mtDNA copy number were observed between hypertension patients and healthy controls. However, in both case and control groups, the mtDNA copy number was statistically significantly lower in the elder population (≥45 years old) compared with the younger subjects (associated with hypertension in coal miners.

Counting the founders: the matrilineal genetic ancestry of the Jewish Diaspora.

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Behar, Doron M; Metspalu, Ene; Kivisild, Toomas; Rosset, Saharon; Tzur, Shay; Hadid, Yarin; Yudkovsky, Guennady; Rosengarten, Dror; Pereira, Luisa; Amorim, Antonio; Kutuev, Ildus; Gurwitz, David; Bonne-Tamir, Batsheva; Villems, Richard; Skorecki, Karl

2008-04-30

The history of the Jewish Diaspora dates back to the Assyrian and Babylonian conquests in the Levant, followed by complex demographic and migratory trajectories over the ensuing millennia which pose a serious challenge to unraveling population genetic patterns. Here we ask whether phylogenetic analysis, based on highly resolved mitochondrial DNA (mtDNA) phylogenies can discern among maternal ancestries of the Diaspora. Accordingly, 1,142 samples from 14 different non-Ashkenazi Jewish communities were analyzed. A list of complete mtDNA sequences was established for all variants present at high frequency in the communities studied, along with high-resolution genotyping of all samples. Unlike the previously reported pattern observed among Ashkenazi Jews, the numerically major portion of the non-Ashkenazi Jews, currently estimated at 5 million people and comprised of the Moroccan, Iraqi, Iranian and Iberian Exile Jewish communities showed no evidence for a narrow founder effect, which did however characterize the smaller and more remote Belmonte, Indian and the two Caucasus communities. The Indian and Ethiopian Jewish sample sets suggested local female introgression, while mtDNAs in all other communities studied belong to a well-characterized West Eurasian pool of maternal lineages. Absence of sub-Saharan African mtDNA lineages among the North African Jewish communities suggests negligible or low level of admixture with females of the host populations among whom the African haplogroup (Hg) L0-L3 sub-clades variants are common. In contrast, the North African and Iberian Exile Jewish communities show influence of putative Iberian admixture as documented by mtDNA Hg HV0 variants. These findings highlight striking differences in the demographic history of the widespread Jewish Diaspora.

Analysis of mtDNA sequence variants in colorectal adenomatous polyps

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Grizzle William

2010-10-01

Full Text Available Abstract Colorectal tumors mostly arise from sporadic adenomatous polyps. Polyps are defined as a mass of cells that protrudes into the lumen of the colon. Adenomatous polyps are benign neoplasms that, by definition display some characteristics of dysplasia. It has been shown that polyps were benign tumors which may undergo malignant transformation. Adenomatous polyps have been classified into three histologic types; tubular, tubulovillous, and villous with increasing malignant potential. The ability to differentially diagnose these colorectal adenomatous polyps is important for therapeutic intervention. To date, little efforts have been directed to identifying genetic changes involved in adenomatous polyps. This study was designed to examine the relevance of mitochondrial genome alterations in the three adenomatous polyps. Using high resolution restriction endonucleases and PCR-based sequencing, fifty-seven primary fresh frozen tissues of adenomatous polyps (37 tumors and 20 matched surrounding normal tissues obtained from the southern regional Cooperative Human Tissue Network (CHTN and Grady Memorial Hospital at Atlanta were screened with three mtDNA regional primer pairs that spanned 5.9 kbp. Results from our data analyses revealed the presence of forty-four variants in some of these mitochondrial genes that the primers spanned; COX I, II, III, ATP 6, 8, CYT b, ND 5, 6 and tRNAs. Based on the MITODAT database as a sequence reference, 25 of the 44 (57% variants observed were unreported. Notably, a heteroplasmic variant C8515G/T in the MT-ATP 8 gene and a germline variant 8327delA in the tRNAlys was observed in all the tissue samples of the three adenomatous polyps in comparison to the referenced database sequence. A germline variant G9055A in the MT-ATP 6 gene had a frequency of 100% (17/17 in tubular and 57% (13/23 in villous adenomas; no corresponding variant was in tubulovillous adenomas. Furthermore, A9006G variant at MT-ATP 6 gene was

Major genomic mitochondrial lineages delineate early human expansions

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Flores Carlos

2001-08-01

Full Text Available Abstract Background The phylogeographic distribution of human mitochondrial DNA variations allows a genetic approach to the study of modern Homo sapiens dispersals throughout the world from a female perspective. As a new contribution to this study we have phylogenetically analysed complete mitochondrial DNA(mtDNA sequences from 42 human lineages, representing major clades with known geographic assignation. Results We show the relative relationships among the 42 lineages and present more accurate temporal calibrations than have been previously possible to give new perspectives as how modern humans spread in the Old World. Conclusions The first detectable expansion occurred around 59,000–69,000 years ago from Africa, independently colonizing western Asia and India and, following this southern route, swiftly reaching east Asia. Within Africa, this expansion did not replace but mixed with older lineages detectable today only in Africa. Around 39,000–52,000 years ago, the western Asian branch spread radially, bringing Caucasians to North Africa and Europe, also reaching India, and expanding to north and east Asia. More recent migrations have entangled but not completely erased these primitive footprints of modern human expansions.

Y-chromosome lineages in native South American population.

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Blanco-Verea, A; Jaime, J C; Brión, M; Carracedo, A

2010-04-01

The present work tries to investigate the population structure and variation of the Amerindian indigenous populations living in Argentina. A total of 134 individuals from three ethnic groups (Kolla, Mapuche and Diaguitas) living in four different regions were collected and analysed for 26 Y-SNPs and 11 Y-STRs. Intra-population variability was analysed, looking for population substructure and neighbour populations were considered for genetic comparative analysis, in order to estimate the contribution of the Amerindian and the European pool, to the current population. We observe a high frequency of R1b1 and Q1a3a* Y-chromosome haplogroups, in the ethnic groups Mapuche, Diaguita and Kolla, characteristic of European and Native American populations, respectively. When we compare our native Argentinean population with other from the South America we also observe that frequency values for Amerindian lineages are relatively lower in our population. These results show a clear Amerindian genetic component but we observe a predominant European influence too, suggesting that typically European male lineages have given rise to the displacement of genuinely Amerindian male lineages in our South American population. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Male infertility is significantly associated with multiple deletions in an 8.7-kb segment of sperm mtDNA in Pakistan.

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Mughal, Irfan Afzal; Irfan, Asma; Jahan, Sarwat; Hameed, Abdul

2017-06-12

This study aimed to find a link between sperm mitochondrial DNA mutations and male infertility in Pakistan. DNA from semen samples was extracted and amplified by PCR using 7.8-kb deletion-specific primers. The PCR products were separated on agarose gel, visualized under UV-illumination, and then photographed. The results were genotyped and the data were analyzed using SPSS. Deletion analysis of the 8.7-kb fragment by long PCR revealed multiple deletions. The frequency of deletion was much higher in infertile groups as compared to the control group. Further, on comparison between different subtypes of infertile groups, the deletions were highest in the oligoasthenoteratozoospermia (OAT) group. The statistical analysis of case and control groups showed a significant association of the 8.7-kb deletion with human male infertile groups (P = 0.031), and particularly a very significant association with the OAT subgroup (P = 0.019). A significant association has been found between human male infertility and mtDNA deletions in an 8.7-kb segment of sperm mtDNA in a Pakistani population.

The fps/fes proto-oncogene regulates hematopoietic lineage output.

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Sangrar, Waheed; Gao, Yan; Zirngibl, Ralph A; Scott, Michelle L; Greer, Peter A

2003-12-01

The fps/fes proto-oncogene is abundantly expressed in myeloid cells, and the Fps/Fes cytoplasmic protein-tyrosine kinase is implicated in signaling downstream from hematopoietic cytokines, including interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (EPO). Studies using leukemic cell lines have previously suggested that Fps/Fes contributes to granulomonocytic differentiation, and that it might play a more selective role in promoting survival and differentiation along the monocytic pathway. In this study we have used a genetic approach to explore the role of Fps/Fes in hematopoiesis. We used transgenic mice that tissue-specifically express a mutant human fps/fes transgene (fps(MF)) that was engineered to encode Fps/Fes kinase that is activated through N-terminal myristoylation (MFps). Hematopoietic function was assessed using lineage analysis, hematopoietic progenitor cell colony-forming assays, and biochemical approaches. fps(MF) transgenic mice displayed a skewed hematopoietic output reflected by increased numbers of circulating granulocytic and monocytic cells and a corresponding decrease in lymphoid cells. Bone marrow colony assays of progenitor cells revealed a significant increase in the number of both granulomonocytic and multi-lineage progenitors. A molecular analysis of signaling in mature monocytic cells showed that MFps promoted GM-CSF-induced STAT3, STAT5, and ERK1/2 activation. These observations support a role for Fps/Fes in signaling pathways that contribute to lineage determination at the level of multi-lineage hematopoietic progenitors as well as the more committed granulomonocytic progenitors.

Lineage Divergence Detected in the Malaria Vector Anopheles marajoara (Diptera: Culicidae) in Amazonian Brazil

Science.gov (United States)

2010-10-07

species [22], but see Bourke et al [17]. Genealogical analyses of complete mtDNA COI (Cyto- chrome oxidase I) sequences found that A. marajoara is...darlingi in human malaria transmission in Boa Vista, state of Roraima, Brazil. Mem Inst Oswaldo Cruz 2006, 101:163-168. 17. Bourke BP, Foster PG

A snapshot of genetic lineages of Mycobacterium tuberculosis in Ireland over a two-year period, 2010 and 2011.

LENUS (Irish Health Repository)

Fitzgibbon, M M

2013-01-01

Mycobacterial interspersed repetitive-unit-variable-number tandem repeat typing alone was used to investigate the genetic lineages among 361 Mycobacterium tuberculosis strains circulating in Ireland over a two-year period, 2010 and 2011. The majority of isolates, 63% (229\\/361), belonged to lineage 4 (Euro-American), while lineages 1 (Indo-Oceanic), 2 (East-Asian) and 3 (East-African–Indian) represented 12% of isolates each (42\\/361, 45\\/361, and 45\\/361, respectively). Sub-lineages Beijing (lineage 2), East-African–Indian (lineage 1) and Delhi\\/central-Asian (lineage 3) predominated among foreign-born cases, while a higher proportion of Euro-American lineages were identified among cases born in Ireland. Eighteen molecular clusters involving 63 tuberculosis (TB) cases were identified across four sub-lineages of lineage 4. While the mean cluster size was 3.5 TB cases, the largest cluster (involving 12 Irish-born cases) was identified in the Latin American–Mediterranean sub-lineage. Clustering of isolates was higher among Irish-born TB cases (47 of 63 clustered cases), whereas only one cluster (3\\/63) involved solely foreign-born individuals. Four multidrug-resistant cases identified during this period represented lineages 2 and 4. This study provides the first insight into the structure of the M. tuberculosis population in Ireland.

Siberian population of the New Stone Age: mtDNA haplotype diversity in the ancient population from the Ust'-Ida I burial ground, dated 4020-3210 BC by 14C.

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Naumova O, Y u; Rychkov S, Y u

1998-03-01

On the basis of analysis of mtDNA from skeletal remains, dated by 14C 4020-3210 BC, from the Ust'-Ida I Neolithic burial ground in Cis-Baikal area of Siberia, we obtained genetic characteristics of the ancient Mongoloid population. Using the 7 restriction enzymes for the analysis of site's polymorphism in 16,106-16,545 region of mtDNA, we studied the structure of the most frequent DNA haplotypes, and estimated the intrapopulational nucleotide diversity of the Neolithic population. Comparison of the Neolithic and modern indigeneous populations from Siberia, Mongolia and Ural showed, that the ancient Siberian population is one of the ancestors of the modern population of Siberia. From genetic distance, in the assumption of constant nucleotide substitution rate, we estimated the divergence time between the Neolithic and the modern Siberian population. This divergence time (5572 years ago) is conformed to the age of skeletal remains (5542-5652 years). With use of the 14C dates of the skeletal remains, nucleotide substitution rate in mtDNA was estimated as 1% sequence divergence for 8938-9115 years.

Lineage fate of ductular reactions in liver injury and carcinogenesis.

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Jörs, Simone; Jeliazkova, Petia; Ringelhan, Marc; Thalhammer, Julian; Dürl, Stephanie; Ferrer, Jorge; Sander, Maike; Heikenwalder, Mathias; Schmid, Roland M; Siveke, Jens T; Geisler, Fabian

2015-06-01

Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary differentiation toward the hepatocyte lineage. Further, lineage-labeled DRs did not produce tumors in genetic and chemical HCC mouse models. In summary, we found no evidence in our system to support mouse biliary-derived DRs as an LPC pool to replenish hepatocytes in a quantitatively relevant way in injury or evidence that DRs give rise to HCCs.

Is the diversification of Mediterranean Basin plant lineages coupled to karyotypic changes?

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Escudero, M; Balao, F; Martín-Bravo, S; Valente, L; Valcárcel, V

2018-01-01

The Mediterranean Basin region, home to 25,000 plant species, is included in the worldwide list of hotspots of biodiversity. Despite the indisputably important role of chromosome transitions in plant evolution and diversification, no reference study to date has dealt with the possible relationship between chromosome evolution and lineage diversification in the Mediterranean Basin. Here we study patterns of diversification, patterns of chromosome number transition (either polyploidy or dysploidy) and the relationship between the two for 14 Mediterranean Basin angiosperm lineages using previously published phylogenies. We found a mixed pattern, with half of the lineages displaying a change in chromosome transition rates after the onset of the Mediterranean climate (six increases, one decrease) and the other half (six) experiencing constant rates of chromosome transitions through time. We have also found a heterogeneous pattern regarding diversification rates, with lineages exhibiting moderate (five phylogenies) or low (six) initial diversification rates that either increased (six) or declined (five) through time. Our results reveal no clear link between diversification rates and chromosome number transition rates. By promoting the formation of new habitats and driving the extinction of many species, the Mediterranean onset and the posterior Quaternary climatic oscillations could have been key for the establishment of new chromosomal variants in some plant phylogenies but not in others. While the biodiversity of the Mediterranean Basin may be partly influenced by the chromosomal diversity of its lineages, this study concludes that lineage diversification in the region is largely decoupled from karyotypic evolution. © 2017 German Botanical Society and The Royal Botanical Society of the Netherlands.

Inferring the population expansions in peopling of Japan.

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Min-Sheng Peng

Full Text Available Extensive studies in different fields have been performed to reconstruct the prehistory of populations in the Japanese archipelago. Estimates the ancestral population dynamics based on Japanese molecular sequences can extend our understanding about the colonization of Japan and the ethnogenesis of modern Japanese.We applied Bayesian skyline plot (BSP with a dataset based on 952 Japanese mitochondrial DNA (mtDNA genomes to depict the female effective population size (N(ef through time for the total Japanese and each of the major mtDNA haplogroups in Japanese. Our results revealed a rapid N(ef growth since ∼5 thousand years ago had left ∼72% Japanese mtDNA lineages with a salient signature. The BSP for the major mtDNA haplogroups indicated some different demographic history.The results suggested that the rapid population expansion acted as a major force in shaping current maternal pool of Japanese. It supported a model for population dynamics in Japan in which the prehistoric population growth initiated in the Middle Jomon Period experienced a smooth and swift transition from Jomon to Yayoi, and then continued through the Yayoi Period. The confounding demographic backgrounds of different mtDNA haplogroups could also have some implications for some related studies in future.

Mitochondrial DNA (mtDNA haplogroups and serum levels of anti-oxidant enzymes in patients with osteoarthritis

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Fernandez-Moreno Mercedes

2011-11-01

Full Text Available Abstract Background Oxidative stress play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. To prevent this, the chondrocytes possess a well-coordinated enzymatic antioxidant system. Besides, the mitochondrial DNA (mtDNA haplogroups are associated with the OA disease. Thus, the main goal of this work is to assess the incidence of the mtDNA haplogroups on serum levels of two of the main antioxidant enzymes, Manganese Superoxide Dismutase (Mn-SOD or SOD2 and catalase, and to test the suitability of these two proteins for potential OA-related biomarkers. Methods We analyzed the serum levels of SOD2 and catalase in 73 OA patients and 77 healthy controls carrying the haplogroups J, U and H, by ELISA assay. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L scoring from Grade 0 to Grade IV. Appropriate statistical analyses were performed to test the effects of clinical variables, including gender, body mass index (BMI, age, smoking status, diagnosis, haplogroups and radiologic K/L grade on serum levels of these enzymes. Results Serum levels of SOD2 appeared statistically increased in OA patients when compared with healthy controls (p Conclusions The increased levels of SOD2 in OA patients indicate an increased oxidative stress OA-related, therefore this antioxidant enzyme could be a suitable candidate biomarker for diagnosis of OA. Mitochondrial haplogroups significantly correlates with serum levels of catalase

Virulence, sporulation, and elicitin production in three clonal lineages of Phytophthora ramorum

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Phytophthora ramorum populations are clonal and consist of three lineages. Recent studies have shown that the clonal lineages may have varying degrees of aggressiveness on some host species, such as Quercus rubra. In this study, we examined virulence, sporulation and elicitin production of five P. ...

Tracing the phylogeography of human populations in Britain based on 4th-11th century mtDNA genotypes.

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Töpf, A L; Gilbert, M T P; Dumbacher, J P; Hoelzel, A R

2006-01-01

Some of the transitional periods of Britain during the first millennium A.D. are traditionally associated with the movement of people from continental Europe, composed largely of invading armies (e.g., the Roman, Saxon, and Viking invasions). However, the extent to which these were migrations (as opposed to cultural exchange) remains controversial. We investigated the history of migration by women by amplifying mitochondrial DNA (mtDNA) from ancient Britons who lived between approximately A.D. 300-1,000 and compared these with 3,549 modern mtDNA database genotypes from England, Europe, and the Middle East. The objective was to assess the dynamics of the historical population composition by comparing genotypes in a temporal context. Towards this objective we test and calibrate the use of rho statistics to identify relationships between founder and source populations. We find evidence for shared ancestry between the earliest sites (predating Viking invasions) with modern populations across the north of Europe from Norway to Estonia, possibly reflecting common ancestors dating back to the last glacial epoch. This is in contrast with a late Saxon site in Norwich, where the genetic signature is consistent with more recent immigrations from the south, possibly as part of the Saxon invasions.

Optimizing and accelerating the assignation of lineages in Mycobacterium tuberculosis using novel alternative single-tube assays.

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María Carcelén

Full Text Available The assignation of lineages in Mycobacterium tuberculosis (MTB provides valuable information for evolutionary and phylogeographic studies and makes for more accurate knowledge of the distribution of this pathogen worldwide. Differences in virulence have also been found for certain lineages. MTB isolates were initially assigned to lineages based on data obtained from genotyping techniques, such as spoligotyping or MIRU-VNTR analysis, some of which are more suitable for molecular epidemiology studies. However, since these methods are subject to a certain degree of homoplasy, other criteria have been chosen to assign lineages. These are based on targeting robust and specific SNPs for each lineage. Here, we propose two newly designed multiplex targeting methods-both of which are single-tube tests-to optimize the assignation of the six main lineages in MTB. The first method is based on ASO-PCR and offers an inexpensive and easy-to-implement assay for laboratories with limited resources. The other, which is based on SNaPshot, enables more refined standardized assignation of lineages for laboratories with better resources. Both methods performed well when assigning lineages from cultured isolates from a control panel, a test panel, and a problem panel from an unrelated population, Mexico, which included isolates in which standard genotyping was not able to classify lineages. Both tests were also able to assign lineages from stored isolates, without the need for subculture or purification of DNA, and even directly from clinical specimens with a medium-high bacilli burden. Our assays could broaden the contexts where information on lineages can be acquired, thus enabling us to quickly update data from retrospective collections and to merge data with those obtained at the time of diagnosis of a new TB case.

Phylogeography of the Rickett's big-footed bat, Myotis pilosus (Chiroptera: Vespertilionidae): a novel pattern of genetic structure of bats in China.

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Lu, Guanjun; Lin, Aiqing; Luo, Jinhong; Blondel, Dimitri V; Meiklejohn, Kelly A; Sun, Keping; Feng, Jiang

2013-11-05

China is characterized by complex topographic structure and dramatic palaeoclimatic changes, making species biogeography studies particularly interesting. Previous researchers have also demonstrated multiple species experienced complex population histories, meanwhile multiple shelters existed in Chinese mainland. Despite this, species phylogeography is still largely unexplored. In the present study, we used a combination of microsatellites and mitochondrial DNA (mtDNA) to investigate the phylogeography of the east Asian fish-eating bat (Myotis pilosus). Phylogenetic analyses showed that M. pilosus comprised three main lineages: A, B and C, which corresponded to distinct geographic populations of the Yangtze Plain (YTP), Sichuan Basin (SCB) and North and South of China (NSC), respectively. The most recent common ancestor of M. pilosus was dated as 0.25 million years before present (BP). Population expansion events were inferred for populations of Clade C, North China Plain region, Clade B and YunGui Plateau region at 38,700, 15,900, 4,520 and 4,520 years BP, respectively. Conflicting results were obtained from mtDNA and microsatellite analyses; strong population genetic structure was obtained from mtDNA data but not microsatellite data. The microsatellite data indicated that genetic subdivision fits an isolation-by-distance (IBD) model, but the mtDNA data failed to support this model. Our results suggested that Pleistocene climatic oscillations might have had a profound influence on the demographic history of M. pilosus. Spatial genetic structures of maternal lineages that are different from those observed in other sympatric bats species may be as a result of interactions among special population history and local environmental factors. There are at least three possible refugia for M. pilosus during glacial episodes. Apparently contradictory genetic structure patterns of mtDNA and microsatellite could be explained by male-mediated gene flow among populations. This

Genotypic lineages and restriction fragment length polymorphism of canine distemper virus isolates in Thailand.

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Radtanakatikanon, Araya; Keawcharoen, Juthatip; Charoenvisal, Na Taya; Poovorawan, Yong; Prompetchara, Eakachai; Yamaguchi, Ryoji; Techangamsuwan, Somporn

2013-09-27

Canine distemper virus (CDV) is known to cause multisystemic disease in all families of terrestrial carnivores. Attenuated live vaccines have been used to control CDV in a variety of species for many decades, yet a number of CDV infections in vaccinated dogs are still observed. The aims of this study were to investigate the genetic diversity of CDV lineages based on phosphoprotein (P), hemagglutinin (H) and fusion protein (F) genes and to develop the restriction fragment length polymorphism (RFLP) technique for effective differentiation among individual wild-type and vaccine lineages in Thailand. Four commercial vaccine products, thirteen conjunctival swabs and various tissues from 9 necropsied dogs suspected of having CDV infections were included. Virus isolation was performed using Vero cell expressing canine signaling lymphocyte activation molecules (Vero-DST cells). Reverse-transcription polymerase chain reaction (RT-PCR) on 3 gene regions from the dog derived specimens and the vaccines were carried out, then RFLP analysis upon F-gene amplified fragments was developed. Nucleotide sequence and phylogenetic analysis were compared with other CDV lineages in Genbank. Phylogenetic relationships revealed that CDV field isolates were separated from the vaccine lineage and could be divided into two clusters; one of which belonged to the Asia-1 lineage and another, not related to any previous recognized lineages was proposed as 'Asia-4'. RFLP patterns demonstrating concordance with phylogenetic trees of the distemper virus allowed for differentiation between the Asia-1, Asia-4 and vaccine lineages. Thus, RFLP technique is able to effectively distinguish individual wild-type canine distemper virus from vaccine lineages in Thailand. Copyright © 2013 Elsevier B.V. All rights reserved.

Tightly congruent bursts of lineage and phenotypic diversification identified in a continental ant radiation.

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Price, Shauna L; Etienne, Rampal S; Powell, Scott

2016-04-01

Adaptive diversification is thought to be shaped by ecological opportunity. A prediction of this ecological process of diversification is that it should result in congruent bursts of lineage and phenotypic diversification, but few studies have found this expected association. Here, we study the relationship between rates of lineage diversification and body size evolution in the turtle ants, a diverse Neotropical clade. Using a near complete, time-calibrated phylogeny we investigated lineage diversification dynamics and body size disparity through model fitting analyses and estimation of per-lineage rates of cladogenesis and phenotypic evolution. We identify an exceptionally high degree of congruence between the high rates of lineage and body size diversification in a young clade undergoing renewed diversification in the ecologically distinct Chacoan biogeographical region of South America. It is likely that the region presented turtle ants with novel ecological opportunity, which facilitated a nested burst of diversification and phenotypic evolution within the group. Our results provide a compelling quantitative example of tight congruence between rates of lineage and phenotypic diversification, meeting the key predicted pattern of adaptive diversification shaped by ecological opportunity. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

Genetic Ancestry using Mitochondrial DNA in patients with Triple-negative breast cancer (GAMiT study).

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Rao, Roshni; Rivers, Aeisha; Rahimi, Asal; Wooldridge, Rachel; Rao, Madhu; Leitch, Marilyn; Euhus, David; Haley, Barbara B

2017-01-01

Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2)/neu receptors, and is aggressive and therapeutically challenging. Genetic ancestry testing is an emerging medical field. Mitochondrial DNA (mtDNA), which is distinct from nuclear DNA, is maternally inherited and allows for origin determination. Patients with TNBC tend to be younger and are more likely to be African American, making this an ideal disease for mtDNA exploration. To the authors' knowledge, the current study is the first to perform mtDNA for self-described African American, White, and Hispanic patients with TNBC to identify mtDNA patterns. Patients with TNBC who were at any stage of therapy/survivorship were included. Self-reported ethnicity was confirmed at the time of the prospective buccal swab. Haplogroup prediction was performed on sequencing of hypervariable region 1. Using sequence similarity scores and lineage databases, sequence patterns were determined. Data regarding presentation and treatment, tumor features, and outcomes was collected. A total of 92 patients were included: 31 self-described African American, 31 White, and 30 Hispanic individuals. Hispanic patients were found to have the largest tumor size (4.5 cm; P = .01) and youngest age (41 years; Pancestry and haplogroups A, U, H, or B to be the most common mtDNA patterns. Twelve discordances (13%) between mtDNA analysis and self-described ethnicity were identified among the 92 patients. The highest discordance (26%; 8 patients) was noted in self-described Hispanic patients: 3 had Nigerian ancestry, and 1 individual demonstrated haplogroup K mtDNA (Ashkenazi Jewish ancestry). Discordance between self-reported ethnicity and mtDNA analysis was identified in 13% of patients with TNBC. The identification of mtDNA patterns with a predisposition toward TNBC may allow for risk stratification. Cancer 2017;107-113. © 2016 American Cancer Society. © 2016 American Cancer

LCGbase: A Comprehensive Database for Lineage-Based Co-regulated Genes.

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Wang, Dapeng; Zhang, Yubin; Fan, Zhonghua; Liu, Guiming; Yu, Jun

2012-01-01

Animal genes of different lineages, such as vertebrates and arthropods, are well-organized and blended into dynamic chromosomal structures that represent a primary regulatory mechanism for body development and cellular differentiation. The majority of genes in a genome are actually clustered, which are evolutionarily stable to different extents and biologically meaningful when evaluated among genomes within and across lineages. Until now, many questions concerning gene organization, such as what is the minimal number of genes in a cluster and what is the driving force leading to gene co-regulation, remain to be addressed. Here, we provide a user-friendly database-LCGbase (a comprehensive database for lineage-based co-regulated genes)-hosting information on evolutionary dynamics of gene clustering and ordering within animal kingdoms in two different lineages: vertebrates and arthropods. The database is constructed on a web-based Linux-Apache-MySQL-PHP framework and effective interactive user-inquiry service. Compared to other gene annotation databases with similar purposes, our database has three comprehensible advantages. First, our database is inclusive, including all high-quality genome assemblies of vertebrates and representative arthropod species. Second, it is human-centric since we map all gene clusters from other genomes in an order of lineage-ranks (such as primates, mammals, warm-blooded, and reptiles) onto human genome and start the database from well-defined gene pairs (a minimal cluster where the two adjacent genes are oriented as co-directional, convergent, and divergent pairs) to large gene clusters. Furthermore, users can search for any adjacent genes and their detailed annotations. Third, the database provides flexible parameter definitions, such as the distance of transcription start sites between two adjacent genes, which is extendable to genes that flanking the cluster across species. We also provide useful tools for sequence alignment, gene

DsbA-L prevents obesity-induced inflammation and insulin resistance by suppressing the mtDNA release-activated cGAS-cGAMP-STING pathway

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Chronic inflammation in adipose tissue plays a key role in obesity-induced insulin resistance. However, the mechanisms underlying obesity-induced inflammation remain elusive. Here we show that obesity promotes mtDNA release into the cytosol, where it triggers inflammatory responses by activating the...

Regal phylogeography: Range-wide survey of the marine angelfish Pygoplites diacanthus reveals evolutionary partitions between the Red Sea, Indian Ocean, and Pacific Ocean.

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Coleman, Richard R; Eble, Jeffrey A; DiBattista, Joseph D; Rocha, Luiz A; Randall, John E; Berumen, Michael L; Bowen, Brian W

2016-07-01

The regal angelfish (Pygoplites diacanthus; family Pomacanthidae) occurs on reefs from the Red Sea to the central Pacific, with an Indian Ocean/Rea Sea color morph distinct from a Pacific Ocean morph. To assess population differentiation and evaluate the possibility of cryptic evolutionary partitions in this monotypic genus, we surveyed mtDNA cytochrome b and two nuclear introns (S7 and RAG2) in 547 individuals from 15 locations. Phylogeographic analyses revealed four mtDNA lineages (d=0.006-0.015) corresponding to the Pacific Ocean, the Red Sea, and two admixed lineages in the Indian Ocean, a pattern consistent with known biogeographic barriers. Christmas Island in the eastern Indian Ocean had both Indian and Pacific lineages. Both S7 and RAG2 showed strong population-level differentiation between the Red Sea, Indian Ocean, and Pacific Ocean (ΦST=0.066-0.512). The only consistent population sub-structure within these three regions was at the Society Islands (French Polynesia), where surrounding oceanographic conditions may reinforce isolation. Coalescence analyses indicate the Pacific (1.7Ma) as the oldest extant lineage followed by the Red Sea lineage (1.4Ma). Results from a median-joining network suggest radiations of two lineages from the Red Sea that currently occupy the Indian Ocean (0.7-0.9Ma). Persistence of a Red Sea lineage through Pleistocene glacial cycles suggests a long-term refuge in this region. The affiliation of Pacific and Red Sea populations, apparent in cytochrome b and S7 (but equivocal in RAG2) raises the hypothesis that the Indian Ocean was recolonized from the Red Sea, possibly more than once. Assessing the genetic architecture of this widespread monotypic genus reveals cryptic evolutionary diversity that merits subspecific recognition. We recommend P.d. diacanthus and P.d. flavescens for the Pacific and Indian Ocean/Red Sea forms. Copyright © 2016 Elsevier Inc. All rights reserved.

Anthropology. Response to Comment on "Late Pleistocene human skeleton and mtDNA link Paleoamericans and modern Native Americans".

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Kemp, Brian M; Lindo, John; Bolnick, Deborah A; Malhi, Ripan S; Chatters, James C

2015-02-20

Prüfer and Meyer raise concerns over the mitochondrial DNA (mtDNA) results we reported for the Hoyo Negro individual, citing failure of a portion of these data to conform to their expectations of ancient DNA (aDNA). Because damage patterns in aDNA vary, outright rejection of our findings on this basis is unwarranted, especially in light of our other observations. Copyright © 2015, American Association for the Advancement of Science.

Mycobacterium tuberculosis Lineage 4 comprises globally distributed and geographically restricted sublineages

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Coscolla, Mireia; Liu, Qingyun; Trauner, Andrej; Fenner, Lukas; Rutaihwa, Liliana; Borrell, Sonia; Luo, Tao; Gao, Qian; Kato-Maeda, Midori; Ballif, Marie; Egger, Matthias; Macedo, Rita; Mardassi, Helmi; Moreno, Milagros; Tudo Vilanova, Griselda; Fyfe, Janet; Globan, Maria; Thomas, Jackson; Jamieson, Frances; Guthrie, Jennifer L.; Asante-Poku, Adwoa; Yeboah-Manu, Dorothy; Wampande, Eddie; Ssengooba, Willy; Joloba, Moses; Henry Boom, W.; Basu, Indira; Bower, James; Saraiva, Margarida; Vaconcellos, Sidra E. G.; Suffys, Philip; Koch, Anastasia; Wilkinson, Robert; Gail-Bekker, Linda; Malla, Bijaya; Ley, Serej D.; Beck, Hans-Peter; de Jong, Bouke C.; Toit, Kadri; Sanchez-Padilla, Elisabeth; Bonnet, Maryline; Gil-Brusola, Ana; Frank, Matthias; Penlap Beng, Veronique N.; Eisenach, Kathleen; Alani, Issam; Wangui Ndung’u, Perpetual; Revathi, Gunturu; Gehre, Florian; Akter, Suriya; Ntoumi, Francine; Stewart-Isherwood, Lynsey; Ntinginya, Nyanda E.; Rachow, Andrea; Hoelscher, Michael; Cirillo, Daniela Maria; Skenders, Girts; Hoffner, Sven; Bakonyte, Daiva; Stakenas, Petras; Diel, Roland; Crudu, Valeriu; Moldovan, Olga; Al-Hajoj, Sahal; Otero, Larissa; Barletta, Francesca; Jane Carter, E.; Diero, Lameck; Supply, Philip; Comas, Iñaki; Niemann, Stefan; Gagneux, Sebastien

2016-01-01

Generalist and specialist species differ in the breadth of their ecological niche. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis Lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that Lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that while the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of Lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration. PMID:27798628

Comparative genomics and transcriptomics of lineages I, II, and III strains of Listeria monocytogenes

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Hain Torsten

2012-04-01

Full Text Available Abstract Background Listeria monocytogenes is a food-borne pathogen that causes infections with a high-mortality rate and has served as an invaluable model for intracellular parasitism. Here, we report complete genome sequences for two L. monocytogenes strains belonging to serotype 4a (L99 and 4b (CLIP80459, and transcriptomes of representative strains from lineages I, II, and III, thereby permitting in-depth comparison of genome- and transcriptome -based data from three lineages of L. monocytogenes. Lineage III, represented by the 4a L99 genome is known to contain strains less virulent for humans. Results The genome analysis of the weakly pathogenic L99 serotype 4a provides extensive evidence of virulence gene decay, including loss of several important surface proteins. The 4b CLIP80459 genome, unlike the previously sequenced 4b F2365 genome harbours an intact inlB invasion gene. These lineage I strains are characterized by the lack of prophage genes, as they share only a single prophage locus with other L. monocytogenes genomes 1/2a EGD-e and 4a L99. Comparative transcriptome analysis during intracellular growth uncovered adaptive expression level differences in lineages I, II and III of Listeria, notable amongst which was a strong intracellular induction of flagellar genes in strain 4a L99 compared to the other lineages. Furthermore, extensive differences between strains are manifest at levels of metabolic flux control and phosphorylated sugar uptake. Intriguingly, prophage gene expression was found to be a hallmark of intracellular gene expression. Deletion mutants in the single shared prophage locus of lineage II strain EGD-e 1/2a, the lma operon, revealed severe attenuation of virulence in a murine infection model. Conclusion Comparative genomics and transcriptome analysis of L. monocytogenes strains from three lineages implicate prophage genes in intracellular adaptation and indicate that gene loss and decay may have led to the emergence

GENETIC DIFFERENTIATION AMONG POPULATIONS OF Chromobotia macracanthus BLEEKER FROM SUMATRA AND KALIMANTAN BASED ON SEQUENCING GENE OF MTDNA CYTOCHROME B AND NUCLEUS DNA RAG2

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Sudarto Sudarto

2008-12-01

Full Text Available Research on genetic differentiation among populations of Chromobotia macracanthus Bleeker from Sumatra, based on sequencing gene of mtDNA Cytochrome b and nucleus DNA RAG2 has been done. The objectives of the study were to obtain the representation of genetic differentiation among population of clown loach fishes or botia (Chromobotia macracanthus from Sumatra and Kalimantan and to estimate the time divergence of both population group of botia. Samples of botia population were taken from 3 rivers in Sumatra namely Batanghari, Musi, and Tulang Bawang and one river from Kalimantan namely Kapuas. The genetic analysis was based on the sequencing of mtDNA Cytochrome b and nucleus DNA RAG2. The statistical analysis was done by using APE package on R language. The parameters observed were: nucleotide diversity, genetic distance, and neighbor-joining tree. The result showed that the highest nucleotide diversity was fish population of Musi, while the other two populations, Tulang Bawang (Sumatra and Kapuas (Kalimantan, were considered as the lowest genetic diversity especially based on nucleus DNA RAG2 sequencing. Based on mtDNA Cytochrome-b sequencing, the most distinct population among those populations based on genetic distance were fish populations of Musi and Kapuas. According to the result of neighbor-joining tree analysis, the populations of botia were classified into two groups namely group of Sumatra and group of Kalimantan. The estimation of time divergence among group of population of Sumatra and Kalimantan based on mtDNA Cytochrome b was about 9.25—9.46 million years (Miocene era. The high genetic differences between groups of Sumatra and Kalimantan suggested that the effort of restocking botia from Sumatra into Kalimantan has to be done carefully, because it may disturb the gene originality of both botia populations.

Exploiting Heparan Sulfate Proteoglycans in Human Neurogenesis—Controlling Lineage Specification and Fate

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Chieh Yu

2017-10-01

Full Text Available Unspecialized, self-renewing stem cells have extraordinary application to regenerative medicine due to their multilineage differentiation potential. Stem cell therapies through replenishing damaged or lost cells in the injured area is an attractive treatment of brain trauma and neurodegenerative neurological disorders. Several stem cell types have neurogenic potential including neural stem cells (NSCs, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and mesenchymal stem cells (MSCs. Currently, effective use of these cells is limited by our lack of understanding and ability to direct lineage commitment and differentiation of neural lineages. Heparan sulfate proteoglycans (HSPGs are ubiquitous proteins within the stem cell microenvironment or niche and are found localized on the cell surface and in the extracellular matrix (ECM, where they interact with numerous signaling molecules. The glycosaminoglycan (GAG chains carried by HSPGs are heterogeneous carbohydrates comprised of repeating disaccharides with specific sulfation patterns that govern ligand interactions to numerous factors including the fibroblast growth factors (FGFs and wingless-type MMTV integration site family (Wnts. As such, HSPGs are plausible targets for guiding and controlling neural stem cell lineage fate. In this review, we provide an overview of HSPG family members syndecans and glypicans, and perlecan and their role in neurogenesis. We summarize the structural changes and subsequent functional implications of heparan sulfate as cells undergo neural lineage differentiation as well as outline the role of HSPG core protein expression throughout mammalian neural development and their function as cell receptors and co-receptors. Finally, we highlight suitable biomimetic approaches for exploiting the role of HSPGs in mammalian neurogenesis to control and tailor cell differentiation into specific lineages. An improved ability to control stem cell specific neural

Pax7 lineage contributions to the mammalian neural crest.

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Barbara Murdoch

Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

Cell tracing reveals a dorsoventral lineage restriction plane in the mouse limb bud mesenchyme.

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Arques, Carlos G; Doohan, Roisin; Sharpe, James; Torres, Miguel

2007-10-01

Regionalization of embryonic fields into independent units of growth and patterning is a widespread strategy during metazoan development. Compartments represent a particular instance of this regionalization, in which unit coherence is maintained by cell lineage restriction between adjacent regions. Lineage compartments have been described during insect and vertebrate development. Two common characteristics of the compartments described so far are their occurrence in epithelial structures and the presence of signaling regions at compartment borders. Whereas Drosophila compartmental organization represents a background subdivision of embryonic fields that is not necessarily related to anatomical structures, vertebrate compartment borders described thus far coincide with, or anticipate, anatomical or cell-type discontinuities. Here, we describe a general method for clonal analysis in the mouse and use it to determine the topology of clone distribution along the three limb axes. We identify a lineage restriction boundary at the limb mesenchyme dorsoventral border that is unrelated to any anatomical discontinuity, and whose lineage restriction border is not obviously associated with any signaling center. This restriction is the first example in vertebrates of a mechanism of primordium subdivision unrelated to anatomical boundaries. Furthermore, this is the first lineage compartment described within a mesenchymal structure in any organism, suggesting that lineage restrictions are fundamental not only for epithelial structures, but also for mesenchymal field patterning. No lineage compartmentalization was found along the proximodistal or anteroposterior axes, indicating that patterning along these axes does not involve restriction of cell dispersion at specific axial positions.

Molecular analyses reveal high species diversity of trematodes in a sub-Arctic lake

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Soldánová, Miroslava; Georgieva, Simona; Roháčováa, Jana; Knudsen, Rune; Kuhn, Jesper A.; Henriksen, Eirik H.; Siwertsson, Anna; Shaw, Jenny C.; Kuris, Armand M.; Amundsen, Per-Arne; Scholz, Tomáš; Lafferty, Kevin D.; Kostadinova, Aneta

2017-01-01

To identify trematode diversity and life-cycles in the sub-Arctic Lake Takvatn, Norway, we characterised 120 trematode isolates from mollusc first intermediate hosts, metacercariae from second intermediate host fishes and invertebrates, and adults from fish and invertebrate definitive hosts, using molecular techniques. Phylogenies based on nuclear and/or mtDNA revealed high species richness (24 species or species-level genetic lineages), and uncovered trematode diversity (16 putative new species) from five families typical in lake ecosystems (Allocreadiidae, Diplostomidae, Plagiorchiidae, Schistosomatidae and Strigeidae). Sampling potential invertebrate hosts allowed matching of sequence data for different stages, thus achieving molecular elucidation of trematode life-cycles and exploration of host-parasite interactions. Phylogenetic analyses also helped identify three major mollusc intermediate hosts (Radix balthica, Pisidium casertanum and Sphaerium sp.) in the lake. Our findings increase the known trematode diversity at the sub-Arctic Lake Takvatn, showing that digenean diversity is high in this otherwise depauperate sub-Arctic freshwater ecosystem, and indicating that sub-Arctic and Arctic ecosystems may be characterised by unique trematode assemblages.

New Lineage of Lassa Virus, Togo, 2016

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Whitmer, Shannon L.M.; Strecker, Thomas; Cadar, Daniel; Dienes, Hans-Peter; Faber, Kelly; Patel, Ketan; Brown, Shelley M.; Davis, William G.; Klena, John D.; Rollin, Pierre E.; Schmidt-Chanasit, Jonas; Fichet-Calvet, Elisabeth; Noack, Bernd; Emmerich, Petra; Rieger, Toni; Wolff, Svenja; Fehling, Sarah Katharina; Eickmann, Markus; Mengel, Jan Philipp; Schultze, Tilman; Hain, Torsten; Ampofo, William; Bonney, Kofi; Aryeequaye, Juliana Naa Dedei; Ribner, Bruce; Varkey, Jay B.; Mehta, Aneesh K.; Lyon, G. Marshall; Kann, Gerrit; De Leuw, Philipp; Schuettfort, Gundolf; Stephan, Christoph; Wieland, Ulrike; Fries, Jochen W.U.; Kochanek, Matthias; Kraft, Colleen S.; Wolf, Timo; Nichol, Stuart T.; Becker, Stephan; Ströher, Ute

2018-01-01

We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo. PMID:29460758

Cells Lacking mtDNA Display Increased dNTP Pools upon DNA Damage

DEFF Research Database (Denmark)

Skovgaard, Tine; Rasmussen, Lene Juel; Munch-Petersen, Birgitte

Imbalanced dNTP pools are highly mutagenic due to a deleterious effect on DNA polymerase fidelity. Mitochondrial DNA defects, including mutations and deletions, are commonly found in a wide variety of different cancer types. In order to further study the interconnection between dNTP pools...... and mitochondrial function we have examined the effect of DNA damage on dNTP pools in cells deficient of mtDNA. We show that DNA damage induced by UV irradiation, in a dose corresponding to LD50, induces an S phase delay in different human osteosarcoma cell lines. The UV pulse also has a destabilizing effect...... shows that normal mitochondrial function is prerequisite for retaining stable dNTP pools upon DNA damage. Therefore it is likely that mitochondrial deficiency defects may cause an increase in DNA mutations by disrupting dNTP pool balance....

The elusive nature of adaptive mitochondrial DNA evolution of an Arctic lineage prone to frequent introgression

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Melo-Ferreira, Jose; Vilela, Joana; Fonseca, Miguel M.

2014-01-01

understood. Hares (Lepus spp.) are privileged models to study the impact of natural selection on mitogenomic evolution because 1) species are adapted to contrasting environments, including arctic, with different metabolic pressures, and 2) mtDNA introgression from arctic into temperate species is widespread...

Ezh2 represses the basal cell lineage during lung endoderm development.

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Snitow, Melinda E; Li, Shanru; Morley, Michael P; Rathi, Komal; Lu, Min Min; Kadzik, Rachel S; Stewart, Kathleen M; Morrisey, Edward E

2015-01-01

The development of the lung epithelium is regulated in a stepwise fashion to generate numerous differentiated and stem cell lineages in the adult lung. How these different lineages are generated in a spatially and temporally restricted fashion remains poorly understood, although epigenetic regulation probably plays an important role. We show that the Polycomb repressive complex 2 component Ezh2 is highly expressed in early lung development but is gradually downregulated by late gestation. Deletion of Ezh2 in early lung endoderm progenitors leads to the ectopic and premature appearance of Trp63+ basal cells that extend the entire length of the airway. Loss of Ezh2 also leads to reduced secretory cell differentiation. In their place, morphologically similar cells develop that express a subset of basal cell genes, including keratin 5, but no longer express high levels of either Trp63 or of standard secretory cell markers. This suggests that Ezh2 regulates the phenotypic switch between basal cells and secretory cells. Together, these findings show that Ezh2 restricts the basal cell lineage during normal lung endoderm development to allow the proper patterning of epithelial lineages during lung formation. © 2015. Published by The Company of Biologists Ltd.

Biogeography and ecology of the rare and abundant microbial lineages in deep-sea hydrothermal vents.

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Anderson, Rika E; Sogin, Mitchell L; Baross, John A

2015-01-01

Environmental gradients generate countless ecological niches in deep-sea hydrothermal vent systems, which foster diverse microbial communities. The majority of distinct microbial lineages in these communities occur in very low abundance. However, the ecological role and distribution of rare and abundant lineages, particularly in deep, hot subsurface environments, remain unclear. Here, we use 16S rRNA tag sequencing to describe biogeographic patterning and microbial community structure of both rare and abundant archaea and bacteria in hydrothermal vent systems. We show that while rare archaeal lineages and almost all bacterial lineages displayed geographically restricted community structuring patterns, the abundant lineages of archaeal communities displayed a much more cosmopolitan distribution. Finally, analysis of one high-volume, high-temperature fluid sample representative of the deep hot biosphere described a unique microbial community that differed from microbial populations in diffuse flow fluid or sulfide samples, yet the rare thermophilic archaeal groups showed similarities to those that occur in sulfides. These results suggest that while most archaeal and bacterial lineages in vents are rare and display a highly regional distribution, a small percentage of lineages, particularly within the archaeal domain, are successful at widespread dispersal and colonization. © FEMS 2014. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Association between Mycobacterium tuberculosis complex phylogenetic lineage and acquired drug resistance.

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Courtney M Yuen

Full Text Available BACKGROUND: Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. METHODS: We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004-2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. RESULTS: M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96-24.14 adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29-15.90 adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56-23.83. CONCLUSIONS: We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management.

Evolution and genome specialization of Brucella suis biovar 2 Iberian lineages.

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Ferreira, Ana Cristina; Tenreiro, Rogério; de Sá, Maria Inácia Corrêa; Dias, Ricardo

2017-09-12

Swine brucellosis caused by B. suis biovar 2 is an emergent disease in domestic pigs in Europe. The emergence of this pathogen has been linked to the increase of extensive pig farms and the high density of infected wild boars (Sus scrofa). In Portugal and Spain, the majority of strains share specific molecular characteristics, which allowed establishing an Iberian clonal lineage. However, several strains isolated from wild boars in the North-East region of Spain are similar to strains isolated in different Central European countries. Comparative analysis of five newly fully sequenced B. suis biovar 2 strains belonging to the main circulating clones in Iberian Peninsula, with publicly available Brucella spp. genomes, revealed that strains from Iberian clonal lineage share 74% similarity with those reference genomes. Besides the 210 kb translocation event present in all biovar 2 strains, an inversion with 944 kb was presented in chromosome I of strains from the Iberian clone. At left and right crossover points, the inversion disrupted a TRAP dicarboxylate transporter, DctM subunit, and an integral membrane protein TerC. The gene dctM is well conserved in Brucella spp. except in strains from the Iberian clonal lineage. Intraspecies comparative analysis also exposed a number of biovar-, haplotype- and strain-specific insertion-deletion (INDELs) events and single nucleotide polymorphisms (SNPs) that could explain differences in virulence and host specificities. Most discriminative mutations were associated to membrane related molecules (29%) and enzymes involved in catabolism processes (20%). Molecular identification of both B. suis biovar 2 clonal lineages could be easily achieved using the target-PCR procedures established in this work for the evaluated INDELs. Whole-genome analyses supports that the B. suis biovar 2 Iberian clonal lineage evolved from the Central-European lineage and suggests that the genomic specialization of this pathogen in the Iberian Peninsula

Extending the generality of leaf economic design principles in the cycads, an ancient lineage.

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Zhang, Yong-Jiang; Cao, Kun-Fang; Sack, Lawren; Li, Nan; Wei, Xue-Mei; Goldstein, Guillermo

2015-04-01

Cycads are the most ancient lineage of living seed plants, but the design of their leaves has received little study. We tested whether cycad leaves are governed by the same fundamental design principles previously established for ferns, conifers and angiosperms, and characterized the uniqueness of this relict lineage in foliar trait relationships. Leaf structure, photosynthesis, hydraulics and nutrient composition were studied in 33 cycad species from nine genera and three families growing in two botanical gardens. Cycads varied greatly in leaf structure and physiology. Similarly to other lineages, light-saturated photosynthetic rate per mass (Am ) was related negatively to leaf mass per area and positively to foliar concentrations of chlorophyll, nitrogen (N), phosphorus and iron, but unlike angiosperms, leaf photosynthetic rate was not associated with leaf hydraulic conductance. Cycads had lower photosynthetic N use efficiency and higher photosynthetic performance relative to hydraulic capacity compared with other lineages. These findings extend the relationships shown for foliar traits in angiosperms to the cycads. This functional convergence supports the modern synthetic understanding of leaf design, with common constraints operating across lineages, even as they highlight exceptional aspects of the biology of this key relict lineage. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Differential trypanocidal activity of novel macrolide antibiotics; correlation to genetic lineage.

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Aquilino, Carolina; Gonzalez Rubio, Maria Luisa; Seco, Elena Maria; Escudero, Leticia; Corvo, Laura; Soto, Manuel; Fresno, Manuel; Malpartida, Francisco; Bonay, Pedro

2012-01-01

Here we report the systematic study of the anti-trypanocidal activity of some new products derived from S. diastatus on 14 different T. cruzi strains spanning the six genetic lineages of T. cruzi. As the traditional growth inhibition curves giving similar IC(50) showed great differences on antibiotic and lineage tested, we decided to preserve the wealth of information derived from each inhibition curve and used an algorithm related to potency of the drugs, combined in a matrix data set used to generate a cluster tree. The cluster thus generated based just on drug susceptibility data closely resembles the phylogenies of the lineages derived from genetic data and provides a novel approach to correlate genetic data with phenotypes related to pathogenesis of Chagas disease. Furthermore we provide clues on the drugs mechanism of action.

Reticulate evolution and incomplete lineage sorting among the ponderosa pines.

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Willyard, Ann; Cronn, Richard; Liston, Aaron

2009-08-01

Interspecific gene flow via hybridization may play a major role in evolution by creating reticulate rather than hierarchical lineages in plant species. Occasional diploid pine hybrids indicate the potential for introgression, but reticulation is hard to detect because ancestral polymorphism is still shared across many groups of pine species. Nucleotide sequences for 53 accessions from 17 species in subsection Ponderosae (Pinus) provide evidence for reticulate evolution. Two discordant patterns among independent low-copy nuclear gene trees and a chloroplast haplotype are better explained by introgression than incomplete lineage sorting or other causes of incongruence. Conflicting resolution of three monophyletic Pinus coulteri accessions is best explained by ancient introgression followed by a genetic bottleneck. More recent hybridization transferred a chloroplast from P. jeffreyi to a sympatric P. washoensis individual. We conclude that incomplete lineage sorting could account for other examples of non-monophyly, and caution against any analysis based on single-accession or single-locus sampling in Pinus.

Pathology of fatal lineage 1 and 2 West Nile virus infections in horses in South Africa

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June H. Williams

2014-09-01

Full Text Available Since 2007, West Nile virus (WNV has been reported in South African horses, causing severe neurological signs. All cases were of lineage 2, except for one case that clustered with lineage 1 viruses. In the present study, gross and microscopic lesions of six South African lineage 2-infected horses and the one lineage 1 case are described. Diagnoses were confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR of central nervous system (CNS tissue and one by RT-PCR of a brain virus isolate. The CNS of all cases was negative by RT-PCR or immunohistochemistry (IHC for African horse sickness (AHS, equine encephalosis virus, equine herpes viruses 1 and 4, other zoonotic flaviviruses, alphaviruses, and shunivirus, and either by immunofluorescence or IHC for rabies. Gross visceral lesions were nonspecific but often mimicked those of AHS. The CNS histopathology of WNV lineage 2 cases resembled the nonsuppurative polioencephalomyelitis reported in the Northern Hemisphere lineage 1 and recent Hungarian lineage 2 cases. Occasional meningitis, focal spinal ventral horn poliomalacia, dorsal and lateral horn poliomyelitis, leucomyelitis, asymmetrical ventral motor spinal neuritis and frequent olfactory region involvement were also seen. Lineage 2 cases displayed marked variations in CNS lesion severity, type and distribution, and suggested various viral entry routes into the CNS, based on findings in experimental mice and hamsters. Lineage 1 lesions were comparable to the milder lineage 2 cases. West Nile virus IHC on CNS sections with marked lesions from all cases elicited only two antigen-positive cells in the olfactory cortex of one case. The presence in the CNS of T-lymphocytes, B-lymphocytes, plasma cells and macrophage-monocytes was confirmed by cluster of differentiation (CD 3, CD20, multiple myeloma oncogene 1 (MUM1 and macrophage (MAC 387 IHC.

Multilocus Phylogeography of the Treefrog Scinax eurydice (Anura, Hylidae) Reveals a Plio-Pleistocene Diversification in the Atlantic Forest

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Menezes, Lucas; Canedo, Clarissa; Batalha-Filho, Henrique; Garda, Adrian Antonio; Gehara, Marcelo; Napoli, Marcelo Felgueiras

2016-01-01

We aim to evaluate the genetic structure of an Atlantic Forest amphibian species, Scinax eurydice, testing the congruence among patterns identified and proposed by the literature for Pleistocene refugia, microrefugia, and geographic barriers to gene flow such as major rivers. Furthermore, we aim to evaluate predictions of such barriers and refugia on the genetic structure of the species, such as presence/absence of dispersal, timing since separation, and population expansions/contractions. We sequenced mitochondrial and nuclear genetic markers on 94 tissue samples from 41 localities. We inferred a gene tree and estimated genetic distances using mtDNA sequences. We then ran population clustering and assignment methods, AMOVA, and estimated migration rates among populations identified through mtDNA and nDNA analyses. We used a dated species tree, skyline plots, and summary statistics to evaluate concordance between population’s distributions and geographic barriers and Pleistocene refugia. Scinax eurydice showed high mtDNA divergences and four clearly distinct mtDNA lineages. Species tree and population assignment tests supported the existence of two major clades corresponding to northeastern and southeastern Atlantic Forest in Brazil, each one composed of two other clades. Lineage splitting events occurred from late Pliocene to Pleistocene. We identified demographic expansions in two clades, and inexistent to low levels of migrations among different populations. Genetic patterns and demographic data support the existence of two northern Refuge and corroborate microrefugia south of the Doce/Jequitinhonha Rivers biogeographic divide. The results agree with a scenario of recent demographic expansion of lowland taxa. Scinax eurydice comprises a species complex, harboring undescribed taxa consistent with Pleistocene refugia. Two rivers lie at the boundaries among populations and endorse their role as secondary barriers to gene flow. PMID:27248688

A Wide Range of 3243A>G/tRNALeu(UUR) (MELAS) Mutation Loads May Segregate in Offspring through the Female Germline Bottleneck

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Pallotti, Francesco; Binelli, Giorgio; Fabbri, Raffaella; Valentino, Maria L.; Vicenti, Rossella; Macciocca, Maria; Cevoli, Sabina; Baruzzi, Agostino; DiMauro, Salvatore; Carelli, Valerio

2014-01-01

Segregation of mutant mtDNA in human tissues and through the germline is debated, with no consensus about the nature and size of the bottleneck hypothesized to explain rapid generational shifts in mutant loads. We investigated two maternal lineages with an apparently different inheritance pattern of the same pathogenic mtDNA 3243A>G/tRNALeu(UUR) (MELAS) mutation. We collected blood cells, muscle biopsies, urinary epithelium and hair follicles from 20 individuals, as well as oocytes and an ovarian biopsy from one female mutation carrier, all belonging to the two maternal lineages to assess mutant mtDNA load, and calculated the theoretical germline bottleneck size (number of segregating units). We also evaluated “mother-to-offspring” segregations from the literature, for which heteroplasmy assessment was available in at least three siblings besides the proband. Our results showed that mutation load was prevalent in skeletal muscle and urinary epithelium, whereas in blood cells there was an inverse correlation with age, as previously reported. The histoenzymatic staining of the ovarian biopsy failed to show any cytochrome-c-oxidase defective oocyte. Analysis of four oocytes and one offspring from the same unaffected mother of the first family showed intermediate heteroplasmic mutant loads (10% to 75%), whereas very skewed loads of mutant mtDNA (0% or 81%) were detected in five offspring of another unaffected mother from the second family. Bottleneck size was 89 segregating units for the first mother and 84 for the second. This was remarkably close to 88, the number of “segregating units” in the “mother-to-offspring” segregations retrieved from literature. In conclusion, a wide range of mutant loads may be found in offspring tissues and oocytes, resulting from a similar theoretical bottleneck size. PMID:24805791

Multilocus Phylogeography of the Treefrog Scinax eurydice (Anura, Hylidae) Reveals a Plio-Pleistocene Diversification in the Atlantic Forest.

Science.gov (United States)

Menezes, Lucas; Canedo, Clarissa; Batalha-Filho, Henrique; Garda, Adrian Antonio; Gehara, Marcelo; Napoli, Marcelo Felgueiras

2016-01-01

We aim to evaluate the genetic structure of an Atlantic Forest amphibian species, Scinax eurydice, testing the congruence among patterns identified and proposed by the literature for Pleistocene refugia, microrefugia, and geographic barriers to gene flow such as major rivers. Furthermore, we aim to evaluate predictions of such barriers and refugia on the genetic structure of the species, such as presence/absence of dispersal, timing since separation, and population expansions/contractions. We sequenced mitochondrial and nuclear genetic markers on 94 tissue samples from 41 localities. We inferred a gene tree and estimated genetic distances using mtDNA sequences. We then ran population clustering and assignment methods, AMOVA, and estimated migration rates among populations identified through mtDNA and nDNA analyses. We used a dated species tree, skyline plots, and summary statistics to evaluate concordance between population's distributions and geographic barriers and Pleistocene refugia. Scinax eurydice showed high mtDNA divergences and four clearly distinct mtDNA lineages. Species tree and population assignment tests supported the existence of two major clades corresponding to northeastern and southeastern Atlantic Forest in Brazil, each one composed of two other clades. Lineage splitting events occurred from late Pliocene to Pleistocene. We identified demographic expansions in two clades, and inexistent to low levels of migrations among different populations. Genetic patterns and demographic data support the existence of two northern Refuge and corroborate microrefugia south of the Doce/Jequitinhonha Rivers biogeographic divide. The results agree with a scenario of recent demographic expansion of lowland taxa. Scinax eurydice comprises a species complex, harboring undescribed taxa consistent with Pleistocene refugia. Two rivers lie at the boundaries among populations and endorse their role as secondary barriers to gene flow.

Evolutionary change in physiological phenotypes along the human lineage.

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Vining, Alexander Q; Nunn, Charles L

2016-01-01

Research in evolutionary medicine provides many examples of how evolution has shaped human susceptibility to disease. Traits undergoing rapid evolutionary change may result in associated costs or reduce the energy available to other traits. We hypothesize that humans have experienced more such changes than other primates as a result of major evolutionary change along the human lineage. We investigated 41 physiological traits across 50 primate species to identify traits that have undergone marked evolutionary change along the human lineage. We analysed the data using two Bayesian phylogenetic comparative methods. One approach models trait covariation in non-human primates and predicts human phenotypes to identify whether humans are evolutionary outliers. The other approach models adaptive shifts under an Ornstein-Uhlenbeck model of evolution to assess whether inferred shifts are more common on the human branch than on other primate lineages. We identified four traits with strong evidence for an evolutionary increase on the human lineage (amylase, haematocrit, phosphorus and monocytes) and one trait with strong evidence for decrease (neutrophilic bands). Humans exhibited more cases of distinct evolutionary change than other primates. Human physiology has undergone increased evolutionary change compared to other primates. Long distance running may have contributed to increases in haematocrit and mean corpuscular haemoglobin concentration, while dietary changes are likely related to increases in amylase. In accordance with the pathogen load hypothesis, human monocyte levels were increased, but many other immune-related measures were not. Determining the mechanisms underlying conspicuous evolutionary change in these traits may provide new insights into human disease. The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

Thimerosal-Derived Ethylmercury Is a Mitochondrial Toxin in Human Astrocytes: Possible Role of Fenton Chemistry in the Oxidation and Breakage of mtDNA

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Martyn A. Sharpe

2012-01-01

Full Text Available Thimerosal generates ethylmercury in aqueous solution and is widely used as preservative. We have investigated the toxicology of Thimerosal in normal human astrocytes, paying particular attention to mitochondrial function and the generation of specific oxidants. We find that ethylmercury not only inhibits mitochondrial respiration leading to a drop in the steady state membrane potential, but also concurrent with these phenomena increases the formation of superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated hydroxyl radical. These oxidants increase the levels of cellular aldehyde/ketones. Additionally, we find a five-fold increase in the levels of oxidant damaged mitochondrial DNA bases and increases in the levels of mtDNA nicks and blunt-ended breaks. Highly damaged mitochondria are characterized by having very low membrane potentials, increased superoxide/hydrogen peroxide production, and extensively damaged mtDNA and proteins. These mitochondria appear to have undergone a permeability transition, an observation supported by the five-fold increase in Caspase-3 activity observed after Thimerosal treatment.

There is no fitness but fitness, and the lineage is its bearer

Science.gov (United States)

2016-01-01

Inclusive fitness has been the cornerstone of social evolution theory for more than a half-century and has matured as a mathematical theory in the past 20 years. Yet surprisingly for a theory so central to an entire field, some of its connections to evolutionary theory more broadly remain contentious or underappreciated. In this paper, we aim to emphasize the connection between inclusive fitness and modern evolutionary theory through the following fact: inclusive fitness is simply classical Darwinian fitness, averaged over social, environmental and demographic states that members of a gene lineage experience. Therefore, inclusive fitness is neither a generalization of classical fitness, nor does it belong exclusively to the individual. Rather, the lineage perspective emphasizes that evolutionary success is determined by the effect of selection on all biological and environmental contexts that a lineage may experience. We argue that this understanding of inclusive fitness based on gene lineages provides the most illuminating and accurate picture and avoids pitfalls in interpretation and empirical applications of inclusive fitness theory. PMID:26729925

There is no fitness but fitness, and the lineage is its bearer.

Science.gov (United States)

Akçay, Erol; Van Cleve, Jeremy

2016-02-05

Inclusive fitness has been the cornerstone of social evolution theory for more than a half-century and has matured as a mathematical theory in the past 20 years. Yet surprisingly for a theory so central to an entire field, some of its connections to evolutionary theory more broadly remain contentious or underappreciated. In this paper, we aim to emphasize the connection between inclusive fitness and modern evolutionary theory through the following fact: inclusive fitness is simply classical Darwinian fitness, averaged over social, environmental and demographic states that members of a gene lineage experience. Therefore, inclusive fitness is neither a generalization of classical fitness, nor does it belong exclusively to the individual. Rather, the lineage perspective emphasizes that evolutionary success is determined by the effect of selection on all biological and environmental contexts that a lineage may experience. We argue that this understanding of inclusive fitness based on gene lineages provides the most illuminating and accurate picture and avoids pitfalls in interpretation and empirical applications of inclusive fitness theory. © 2016 The Author(s).

Lineage tracing of genome-edited alleles reveals high fidelity axolotl limb regeneration.

Science.gov (United States)

Flowers, Grant Parker; Sanor, Lucas D; Crews, Craig M

2017-09-16

Salamanders are unparalleled among tetrapods in their ability to regenerate many structures, including entire limbs, and the study of this ability may provide insights into human regenerative therapies. The complex structure of the limb poses challenges to the investigation of the cellular and molecular basis of its regeneration. Using CRISPR/Cas, we genetically labelled unique cell lineages within the developing axolotl embryo and tracked the frequency of each lineage within amputated and fully regenerated limbs. This allowed us, for the first time, to assess the contributions of multiple low frequency cell lineages to the regenerating limb at once. Our comparisons reveal that regenerated limbs are high fidelity replicas of the originals even after repeated amputations.

Reading Mammal Diversity from Flies: The Persistence Period of Amplifiable Mammal mtDNA in Blowfly Guts (Chrysomya megacephala) and a New DNA Mini-Barcode Target.

Science.gov (United States)

Lee, Ping-Shin; Sing, Kong-Wah; Wilson, John-James

2015-01-01

Most tropical mammal species are threatened or data-deficient. Data collection is impeded by the traditional monitoring approaches which can be laborious, expensive and struggle to detect cryptic diversity. Monitoring approaches using mammal DNA derived from invertebrates are emerging as cost- and time-effective alternatives. As a step towards development of blowfly-derived DNA as an effective method for mammal monitoring in the biodiversity hotspot of Peninsular Malaysia, our objectives were (i) to determine the persistence period of amplifiable mammal mtDNA in blowfly guts through a laboratory feeding experiment (ii) to design and test primers that can selectively amplify mammal COI DNA mini-barcodes in the presence of high concentrations of blowfly DNA. The persistence period of amplifiable mammal mtDNA in blowfly guts was 24 h to 96 h post-feeding indicating the need for collecting flies within 24 h of capture to detect mammal mtDNA of sufficient quantity and quality. We designed a new primer combination for a COI DNA mini-barcode that did not amplify blowfly DNA and showed 89% amplification success for a dataset of mammals from Peninsular Malaysia. The short (205 bp) DNA mini-barcode could distinguish most mammal species (including separating dark taxa) and is of suitable length for high-throughput sequencing. Our new DNA mini-barcode target and a standardized trapping protocol with retrieval of blowflies every 24 h could point the way forward in the development of blowfly-derived DNA as an effective method for mammal monitoring.

Ascl1 (Mash1) lineage cells contribute to discrete cell populations in CNS architecture

OpenAIRE

Kim, Euiseok J.; Battiste, James; Nakagawa, Yasushi; Johnson, Jane E.

2008-01-01

Ascl1 (previously Mash1) is a bHLH transcription factor essential for neuronal differentiation and specification in the nervous system. Although it has been studied for its role in several neural lineages, the full complement of lineages arising from Ascl1 progenitor cells remains unknown. Using an inducible Cre-flox genetic fate mapping strategy, Ascl1 lineages were determined throughout the brain. Ascl1 is present in proliferating progenitor cells but these cells are actively differentiatin...

Speciation on oceanic islands: rapid adaptive divergence vs. cryptic speciation in a Guadalupe Island songbird (Aves: Junco).

Science.gov (United States)

Aleixandre, Pau; Hernández Montoya, Julio; Milá, Borja

2013-01-01

The evolutionary divergence of island populations, and in particular the tempo and relative importance of neutral and selective factors, is of central interest to the study of speciation. The rate of phenotypic evolution upon island colonization can vary greatly among taxa, and cases of convergent evolution can further confound the inference of correct evolutionary histories. Given the potential lability of phenotypic characters, molecular dating of insular lineages analyzed in a phylogenetic framework provides a critical tool to test hypotheses of phenotypic divergence since colonization. The Guadalupe junco is the only insular form of the polymorphic dark-eyed junco (Junco hyemalis), and shares eye and plumage color with continental morphs, yet presents an enlarged bill and reduced body size. Here we use variation in mtDNA sequence, morphological traits and song variables to test whether the Guadalupe junco evolved rapidly following a recent colonization by a mainland form of the dark-eyed junco, or instead represents a well-differentiated "cryptic" lineage adapted to the insular environment through long-term isolation, with plumage coloration a result of evolutionary convergence. We found high mtDNA divergence of the island lineage with respect to both continental J. hyemalis and J. phaeonotus, representing a history of isolation of about 600,000 years. The island lineage was also significantly differentiated in morphological and male song variables. Moreover, and contrary to predictions regarding diversity loss on small oceanic islands, we document relatively high levels of both haplotypic and song-unit diversity on Guadalupe Island despite long-term isolation in a very small geographic area. In contrast to prevailing taxonomy, the Guadalupe junco is an old, well-differentiated evolutionary lineage, whose similarity to mainland juncos in plumage and eye color is due to evolutionary convergence. Our findings confirm the role of remote islands in driving

Targeted Transgenic Overexpression of Mitochondrial Thymidine Kinase (TK2) Alters Mitochondrial DNA (mtDNA) and Mitochondrial Polypeptide Abundance

Science.gov (United States)

Hosseini, Seyed H.; Kohler, James J.; Haase, Chad P.; Tioleco, Nina; Stuart, Tami; Keebaugh, Erin; Ludaway, Tomika; Russ, Rodney; Green, Elgin; Long, Robert; Wang, Liya; Eriksson, Staffan; Lewis, William

2007-01-01

Mitochondrial toxicity limits nucleoside reverse transcriptase inhibitors (NRTIs) for acquired immune deficiency syndrome. NRTI triphosphates, the active moieties, inhibit human immunodeficiency virus reverse transcriptase and eukaryotic mitochondrial DNA polymerase pol-γ. NRTI phosphorylation seems to correlate with mitochondrial toxicity, but experimental evidence is lacking. Transgenic mice (TGs) with cardiac overexpression of thymidine kinase isoforms (mitochondrial TK2 and cytoplasmic TK1) were used to study NRTI mitochondrial toxicity. Echocardiography and nuclear magnetic resonance imaging defined cardiac performance and structure. TK gene copy and enzyme activity, mitochondrial (mt) DNA and polypeptide abundance, succinate dehydrogenase and cytochrome oxidase histochemistry, and electron microscopy correlated with transgenesis, mitochondrial structure, and biogenesis. Antiretroviral combinations simulated therapy. Untreated hTK1 or TK2 TGs exhibited normal left ventricle mass. In TK2 TGs, cardiac TK2 gene copy doubled, activity increased 300-fold, and mtDNA abundance doubled. Abundance of the 17-kd subunit of complex I, succinate dehydrogenase histochemical activity, and cristae density increased. NRTIs increased left ventricle mass 20% in TK2 TGs. TK activity increased 3 logs in hTK1 TGs, but no cardiac phenotype resulted. NRTIs abrogated functional effects of transgenically increased TK2 activity but had no effect on TK2 mtDNA abundance. Thus, NRTI mitochondrial phosphorylation by TK2 is integral to clinical NRTI mitochondrial toxicity. PMID:17322372

Differential trypanocidal activity of novel macrolide antibiotics; correlation to genetic lineage.

Directory of Open Access Journals (Sweden)

Carolina Aquilino

Full Text Available Here we report the systematic study of the anti-trypanocidal activity of some new products derived from S. diastatus on 14 different T. cruzi strains spanning the six genetic lineages of T. cruzi. As the traditional growth inhibition curves giving similar IC(50 showed great differences on antibiotic and lineage tested, we decided to preserve the wealth of information derived from each inhibition curve and used an algorithm related to potency of the drugs, combined in a matrix data set used to generate a cluster tree. The cluster thus generated based just on drug susceptibility data closely resembles the phylogenies of the lineages derived from genetic data and provides a novel approach to correlate genetic data with phenotypes related to pathogenesis of Chagas disease. Furthermore we provide clues on the drugs mechanism of action.

Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A

International Nuclear Information System (INIS)

Wang Huawei; Jia Xiaoyun; Ji Yanli; Kong Qingpeng; Zhang Qingjiong; Yao Yonggang; Zhang Yaping

2008-01-01

The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P < 0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate any putatively pathogenic mutation that cosegregated with G11778A in these two pedigrees. Our results suggest that the variable penetrance of LHON in the two Chinese families is independent of both their mtDNA haplotype background and a secondary mutation G13708A. As a result, it is likely that unknown nuclear gene involvement and/or other factors contribute to the strikingly different penetrance of LHON

Chromosomal barcoding as a tool for multiplexed phenotypic characterization of laboratory evolved lineages

DEFF Research Database (Denmark)

Jahn, Leonie Johanna; Porse, Andreas; Munck, Christian

2018-01-01

experiments can be automated in a high-throughput fashion. However, the characterization of the resulting lineages can become a time consuming task, when the performance of each lineage is evaluated individually. Here, we present a novel method for the markerless insertion of randomized genetic barcodes...

Cytomegalovirus immune evasion of myeloid lineage cells.

Science.gov (United States)

Brinkmann, Melanie M; Dağ, Franziska; Hengel, Hartmut; Messerle, Martin; Kalinke, Ulrich; Čičin-Šain, Luka

2015-06-01

Cytomegalovirus (CMV) evades the immune system in many different ways, allowing the virus to grow and its progeny to spread in the face of an adverse environment. Mounting evidence about the antiviral role of myeloid immune cells has prompted the research of CMV immune evasion mechanisms targeting these cells. Several cells of the myeloid lineage, such as monocytes, dendritic cells and macrophages, play a role in viral control, but are also permissive for CMV and are naturally infected by it. Therefore, CMV evasion of myeloid cells involves mechanisms that qualitatively differ from the evasion of non-CMV-permissive immune cells of the lymphoid lineage. The evasion of myeloid cells includes effects in cis, where the virus modulates the immune signaling pathways within the infected myeloid cell, and those in trans, where the virus affects somatic cells targeted by cytokines released from myeloid cells. This review presents an overview of CMV strategies to modulate and evade the antiviral activity of myeloid cells in cis and in trans.

Mesenchymal progenitor cells for the osteogenic lineage.

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Ono, Noriaki; Kronenberg, Henry M

2015-09-01

Mesenchymal progenitors of the osteogenic lineage provide the flexibility for bone to grow, maintain its function and homeostasis. Traditionally, colony-forming-unit fibroblasts (CFU-Fs) have been regarded as surrogates for mesenchymal progenitors; however, this definition cannot address the function of these progenitors in their native setting. Transgenic murine models including lineage-tracing technologies based on the cre-lox system have proven to be useful in delineating mesenchymal progenitors in their native environment. Although heterogeneity of cell populations of interest marked by a promoter-based approach complicates overall interpretation, an emerging complexity of mesenchymal progenitors has been revealed. Current literatures suggest two distinct types of bone progenitor cells; growth-associated mesenchymal progenitors contribute to explosive growth of bone in early life, whereas bone marrow mesenchymal progenitors contribute to the much slower remodeling process and response to injury that occurs mainly in adulthood. More detailed relationships of these progenitors need to be studied through further experimentation.

Long-term live cell imaging and automated 4D analysis of drosophila neuroblast lineages.

Directory of Open Access Journals (Sweden)

Catarina C F Homem

Full Text Available The developing Drosophila brain is a well-studied model system for neurogenesis and stem cell biology. In the Drosophila central brain, around 200 neural stem cells called neuroblasts undergo repeated rounds of asymmetric cell division. These divisions typically generate a larger self-renewing neuroblast and a smaller ganglion mother cell that undergoes one terminal division to create two differentiating neurons. Although single mitotic divisions of neuroblasts can easily be imaged in real time, the lack of long term imaging procedures has limited the use of neuroblast live imaging for lineage analysis. Here we describe a method that allows live imaging of cultured Drosophila neuroblasts over multiple cell cycles for up to 24 hours. We describe a 4D image analysis protocol that can be used to extract cell cycle times and growth rates from the resulting movies in an automated manner. We use it to perform lineage analysis in type II neuroblasts where clonal analysis has indicated the presence of a transit-amplifying population that potentiates the number of neurons. Indeed, our experiments verify type II lineages and provide quantitative parameters for all cell types in those lineages. As defects in type II neuroblast lineages can result in brain tumor formation, our lineage analysis method will allow more detailed and quantitative analysis of tumorigenesis and asymmetric cell division in the Drosophila brain.

Occurrence of different Canine distemper virus lineages in Italian dogs.

Science.gov (United States)

Balboni, Andrea; De Lorenzo Dandola, Giorgia; Scagliarini, Alessandra; Prosperi, Santino; Battilani, Mara

2014-01-01

This study describes the sequence analysis of the H gene of 7 Canine distemper virus (CDV) strains identified in dogs in Italy between years 2002-2012. The phylogenetic analysis showed that the CDV strains belonged to 2 clusters: 6 viruses were identified as Arctic-like lineage and 1 as Europe 1 lineage. These data show a considerable prevalence of Arctic-like-CDVs in the analysed dogs. The dogs and the 3 viruses more recently identified showed 4 distinctive amino acid mutations compared to all other Arctic CDVs.

Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

KAUST Repository

Phelan, Jody E.

2016-02-29

Background Approximately 10 % of the Mycobacterium tuberculosis genome is made up of two families of genes that are poorly characterized due to their high GC content and highly repetitive nature. The PE and PPE families are typified by their highly conserved N-terminal domains that incorporate proline-glutamate (PE) and proline-proline-glutamate (PPE) signature motifs. They are hypothesised to be important virulence factors involved with host-pathogen interactions, but their high genetic variability and complexity of analysis means they are typically disregarded in genome studies. Results To elucidate the structure of these genes, 518 genomes from a diverse international collection of clinical isolates were de novo assembled. A further 21 reference M. tuberculosis complex genomes and long read sequence data were used to validate the approach. SNP analysis revealed that variation in the majority of the 168 pe/ppe genes studied was consistent with lineage. Several recombination hotspots were identified, notably pe_pgrs3 and pe_pgrs17. Evidence of positive selection was revealed in 65 pe/ppe genes, including epitopes potentially binding to major histocompatibility complex molecules. Conclusions This, the first comprehensive study of the pe and ppe genes, provides important insight into M. tuberculosis diversity and has significant implications for vaccine development.

Phylogenetic features of hemagglutin gene in canine distemper virus strains from different genetic lineages.

Science.gov (United States)

Liao, Peng; Guo, Li; Wen, Yongjun; Yang, Yangling; Cheng, Shipeng

2015-01-01

In the present study, the genotype of two Canine distemper virus (CDV) strains, namely, ZJJ-SD and ZJJ-LN, were investigated, based on the whole hemagglutinin (HA) gene. The CDV strains were obtained from two foxes in Shandong Province and Liaoning Province in 2011. Phylogenetic analyses were carried out for 260 CDV strains worldwide, and a statistical analysis was performed in the amino acid substitutions at positions 530 and 549 of the HA protein. Phylogenetic analyses revealed that the two strains, ZJJ-SD and ZJJ-LN, belonged to the CDV Asia I lineage. Site 530 of HA protein was found to be relatively conserved within CDV lineages in different host species by combining the genetic sequence data with the published data from 260 CDV strains worldwide. The data analysis showed a bias toward the predicted substitution Y549H for the non-dog strains in Asia I and Europe lineages. The ratio of site 549 genetic drift in the HA gene were significantly different between dogs and non-dogs in the two lineages. The strain ZJJ-SD, from wild canid, has an Y549H substitution. It is one of three Y549H substitution for wild canids in Asia I lineages. Site 530 of HA protein was not immediately relative to CDV genetic drift from dogs to non-dogs. Statistical analysis indicated that non-dog strains have a high probability to contain Y549H than dog strains in Asia I and Europe lineages. Thus, site 549 is considered important in genetic drift from dogs to non-dogs, at least in Asia I and Europe lineages.

The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific

DEFF Research Database (Denmark)

Raule, Nicola; Sevini, Federica; Li, Shengting

2014-01-01

To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification...

Species phylogeny and diversification process of Northeast Asian Pungitius revealed by AFLP and mtDNA markers

DEFF Research Database (Denmark)

Takahashi, Hiroshi; Møller, Peter Rask; Shedko, Sergei V.

2016-01-01

Pungitius is a highly diversified genus of sticklebacks (Gasterosteidae) occurring widely in northern parts of the Northern Hemisphere. Several ecologically and genetically divergent types that are largely isolated reproductively but occasionally hybridize in sympatry have been discovered...... of hybridization and mtDNA introgression among distinct species. Our results highlight that the marginal seas of Northeast Asia played a key role as barriers to or facilitators of gene flow in the evolution of species diversity of Pungitius concentrated in this region...

MELAS and Kearns–Sayre overlap syndrome due to the mtDNA m. A3243G mutation and large-scale mtDNA deletions

Directory of Open Access Journals (Sweden)

Nian Yu

2016-09-01

Full Text Available This paper reported an unusual manifestation of a 19-year-old Chinese male patient presented with a complex phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS syndrome and Kearns–Sayre syndrome (KSS. He was admitted to our hospital with the chief complaint of “acute fever, headache and slow reaction for 21 days”. He was initially misdiagnosed as “viral encephalitis”. This Chinese man with significant past medical history of intolerating fatigue presented paroxysmal neurobehavioral attacks that started about 10 years ago. During this span, 3 or 4 attack clusters were described during which several attacks occurred over a few days. The further examination found that the hallmark signs of this patient included progressive myoclonus epilepsy, cerebellar ataxia, hearing loss, myopathic weakness, ophthalmoparesis, pigmentary retinopathy and bifascicular heart block (Wolff–Parkinson–White syndrome. By young age the disease progression is characterized by the addition of migraine, vomiting, and stroke-like episodes, symptoms of MELAS expression, which indicated completion of the MELAS/KSS overlap syndrome. The m. A3243G mitochondrial DNA mutation and single large-scale mtDNA deletions were found in this patient. This mutation has been reported with MELAS, KSS, myopathy, deafness and mental disorder with cognitive impairment. This is the first description with a MELAS/KSS syndrome in Chinese.

Pox neuro control of cell lineages that give rise to larval poly-innervated external sensory organs in Drosophila.

Science.gov (United States)

Jiang, Yanrui; Boll, Werner; Noll, Markus

2015-01-15

The Pox neuro (Poxn) gene of Drosophila plays a crucial role in the development of poly-innervated external sensory (p-es) organs. However, how Poxn exerts this role has remained elusive. In this study, we have analyzed the cell lineages of all larval p-es organs, namely of the kölbchen, papilla 6, and hair 3. Surprisingly, these lineages are distinct from any previously reported cell lineages of sensory organs. Unlike the well-established lineage of mono-innervated external sensory (m-es) organs and a previously proposed model of the p-es lineage, we demonstrate that all wild-type p-es lineages exhibit the following features: the secondary precursor, pIIa, gives rise to all three support cells-socket, shaft, and sheath, whereas the other secondary precursor, pIIb, is neuronal and gives rise to all neurons. We further show that in one of the p-es lineages, that of papilla 6, one cell undergoes apoptosis. By contrast in Poxn null mutants, all p-es lineages have a reduced number of cells and their pattern of cell divisions is changed to that of an m-es organ, with the exception of a lineage in a minority of mutant kölbchen that retains a second bipolar neuron. Indeed, the role of Poxn in p-es lineages is consistent with the specification of the developmental potential of secondary precursors and the regulation of cell division but not apoptosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Asymptotic distributions of coalescence times and ancestral lineage numbers for populations with temporally varying size.

Science.gov (United States)

Chen, Hua; Chen, Kun

2013-07-01

The distributions of coalescence times and ancestral lineage numbers play an essential role in coalescent modeling and ancestral inference. Both exact distributions of coalescence times and ancestral lineage numbers are expressed as the sum of alternating series, and the terms in the series become numerically intractable for large samples. More computationally attractive are their asymptotic distributions, which were derived in Griffiths (1984) for populations with constant size. In this article, we derive the asymptotic distributions of coalescence times and ancestral lineage numbers for populations with temporally varying size. For a sample of size n, denote by Tm the mth coalescent time, when m + 1 lineages coalesce into m lineages, and An(t) the number of ancestral lineages at time t back from the current generation. Similar to the results in Griffiths (1984), the number of ancestral lineages, An(t), and the coalescence times, Tm, are asymptotically normal, with the mean and variance of these distributions depending on the population size function, N(t). At the very early stage of the coalescent, when t → 0, the number of coalesced lineages n - An(t) follows a Poisson distribution, and as m → n, $$n\\left(n-1\\right){T}_{m}/2N\\left(0\\right)$$ follows a gamma distribution. We demonstrate the accuracy of the asymptotic approximations by comparing to both exact distributions and coalescent simulations. Several applications of the theoretical results are also shown: deriving statistics related to the properties of gene genealogies, such as the time to the most recent common ancestor (TMRCA) and the total branch length (TBL) of the genealogy, and deriving the allele frequency spectrum for large genealogies. With the advent of genomic-level sequencing data for large samples, the asymptotic distributions are expected to have wide applications in theoretical and methodological development for population genetic inference.

Lineage range estimation method reveals fine-scale endemism linked to Pleistocene stability in Australian rainforest herpetofauna.

Science.gov (United States)

Rosauer, Dan F; Catullo, Renee A; VanDerWal, Jeremy; Moussalli, Adnan; Moritz, Craig

2015-01-01

Areas of suitable habitat for species and communities have arisen, shifted, and disappeared with Pleistocene climate cycles, and through this shifting landscape, current biodiversity has found paths to the present. Evolutionary refugia, areas of relative habitat stability in this shifting landscape, support persistence of lineages through time, and are thus crucial to the accumulation and maintenance of biodiversity. Areas of endemism are indicative of refugial areas where diversity has persisted, and endemism of intraspecific lineages in particular is strongly associated with late-Pleistocene habitat stability. However, it remains a challenge to consistently estimate the geographic ranges of intraspecific lineages and thus infer phylogeographic endemism, because spatial sampling for genetic analyses is typically sparse relative to species records. We present a novel technique to model the geographic distribution of intraspecific lineages, which is informed by the ecological niche of a species and known locations of its constituent lineages. Our approach allows for the effects of isolation by unsuitable habitat, and captures uncertainty in the extent of lineage ranges. Applying this method to the arc of rainforest areas spanning 3500 km in eastern Australia, we estimated lineage endemism for 53 species of rainforest dependent herpetofauna with available phylogeographic data. We related endemism to the stability of rainforest habitat over the past 120,000 years and identified distinct concentrations of lineage endemism that can be considered putative refugia. These areas of lineage endemism are strongly related to historical stability of rainforest habitat, after controlling for the effects of current environment. In fact, a dynamic stability model that allows movement to track suitable habitat over time was the most important factor in explaining current patterns of endemism. The techniques presented here provide an objective, practical method for estimating

Signatures of natural selection among lineages and habitats in Oncorhynchus mykiss

DEFF Research Database (Denmark)

Limborg, Morten; Blankenship, S.; Young, S.

2012-01-01

lineage. Overall patterns of variation affirmed clear distinctions between lineages and in most instances, isolation by distance within them. Evidence for divergent selection at eight candidate loci included significant landscape correlations, particularly with temperature. High diversity of two...... nonsynonymous mutations within the peptide-binding region of the major histocompatibility complex (MHC) class II (DAB) gene provided signatures of balancing selection. Weak signals for potential selection between sympatric resident and anadromous populations were revealed from genome scans and allele frequency...

Determining the control networks regulating stem cell lineages in colonic crypts

OpenAIRE

Yang, J; Axelrod, DE; Komarova, NL

2017-01-01

The question of stem cell control is at the center of our understanding of tissue functioning, both in healthy and cancerous conditions. It is well accepted that cellular fate decisions (such as divisions, differentiation, apoptosis) are orchestrated by a network of regulatory signals emitted by different cell populations in the lineage and the surrounding tissue. The exact regulatory network that governs stem cell lineages in a given tissue is usually unknown. Here we propose an algorithm to...

Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion

Directory of Open Access Journals (Sweden)

Sandra Capellera-Garcia

2016-06-01

Full Text Available Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs. We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.

Effect of lineage-specific metabolic traits of Lactobacillus reuteri on sourdough microbial ecology.

Science.gov (United States)

Lin, Xiaoxi B; Gänzle, Michael G

2014-09-01

This study determined the effects of specific metabolic traits of Lactobacillus reuteri on its competitiveness in sourdoughs. The competitiveness of lactobacilli in sourdough generally depends on their growth rate; acid resistance additionally contributes to competitiveness in sourdoughs with long fermentation times. Glycerol metabolism via glycerol dehydratase (gupCDE) accelerates growth by the regeneration of reduced cofactors; glutamate metabolism via glutamate decarboxylase (gadB) increases acid resistance by generating a proton motive force. Glycerol and glutamate metabolisms are lineage-specific traits in L. reuteri; therefore, this study employed glycerol dehydratase-positive sourdough isolates of human-adapted L. reuteri lineage I, glutamate decarboxylase-positive strains of rodent-adapted L. reuteri lineage II, as well as mutants with deletions in gadB or gupCDE. The competitivenesses of the strains were quantified by inoculation of wheat and sorghum sourdoughs with defined strains, followed by propagation of doughs with a 10% inoculum and 12-h or 72-h fermentation cycles. Lineage I L. reuteri strains dominated sourdoughs propagated with 12-h fermentation cycles; lineage II L. reuteri strains dominated sourdoughs propagated with 72-h fermentation cycles. L. reuteri 100-23ΔgadB was outcompeted by its wild-type strain in sourdoughs fermented with 72-h fermentation cycles; L. reuteri FUA3400ΔgupCDE was outcompeted by its wild-type strain in sourdoughs fermented with both 12-h and 72-h fermentation cycles. Competition experiments with isogenic pairs of strains resulted in a constant rate of strain displacement of the less competitive mutant strain. In conclusion, lineage-specific traits of L. reuteri determine the competitiveness of this species in sourdough fermentations. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Contrasting sodic and mildly potassic magma differentiation lineages at The Pleaides volcanic complex, northern Victoria Land, Antarctica

Science.gov (United States)

Kim, J.; Park, J. W.; Lee, J.; Kyle, P. R.; Lee, M. J.

2017-12-01

The magma evolution of The Pleiades, a Quaternary alkaline volcanic complex in northern Victoria Land, Antarctica, is investigated using major and trace elements, and Sr, Nd and Pb isotopic data. The volcanic rocks can be subdivided into two distinct magmatic lineages based on petrography and whole-rock compositions: (1) a sodic silica-undersaturated alkaline lineage with abundant kaersutite phenocrysts, and (2) a mildly-potassic and mildly-alkaline, nearly silica-saturated lineage containing olivine but not kaersutite. The basanite and trachybasalt of both lineages exhibit similar degrees of negative K anomalies, moderately steep rare earth element patterns, and elevated trace element ratios such as Ce/Pb (> 20) and Nb/U (> 38), suggesting their primary magmas were generated by low degree (≤3%) of partial melting of amphibole and garnet-bearing mantle sources. The sodic lineage is characterized by elevated 206Pb/204Pb (>19.5) ratios and narrow ranges of 87Sr/86Sr (0.70313-0.70327) and 143Nd/144Nd (0.51289-0.51290) ratios consistent with a significant HIMU component typical of Neogene volcanic rocks in Antarctica. The mafic rocks of the potassic lineage have isotopic compositions similar to those of the sodic lineage, however the evolved lavas in the lineage have higher 87Sr/86Sr (> 0.7035) and lower 143Nd/144Nd (< 0.51285) and 206Pb/204Pb (< 19.3) ratios than the mafic rocks, suggesting significant amounts of crustal contamination. The pressure-temperature paths estimated by clinopyroxene-liquid thermobarometry are similar in each lineage. The mafic magmas were emplaced at Moho depths ( 1.2 GPa) and the evolved magmas pooled at middle-crustal depths ( 0.7 GPa). Mass-balance calculations based on whole-rock and mineral compositions show that kaersutite fractionation has played a major role in magma differentiation of the sodic lineage whereas the compositional variations of the potassic lineage can be ascribed to fractionation of a kaersutite-free mineral

Ecological Niche Modelling of the Bacillus anthracis A1.a sub-lineage in Kazakhstan

Science.gov (United States)

2011-01-01

Background Bacillus anthracis, the causative agent of anthrax, is a globally distributed zoonotic pathogen that continues to be a veterinary and human health problem in Central Asia. We used a database of anthrax outbreak locations in Kazakhstan and a subset of genotyped isolates to model the geographic distribution and ecological associations of B. anthracis in Kazakhstan. The aims of the study were to test the influence of soil variables on a previous ecological niche based prediction of B. anthracis in Kazakhstan and to determine if a single sub-lineage of B. anthracis occupies a unique ecological niche. Results The addition of soil variables to the previously developed ecological niche model did not appreciably alter the limits of the predicted geographic or ecological distribution of B. anthracis in Kazakhstan. The A1.a experiment predicted the sub-lineage to be present over a larger geographic area than did the outbreak based experiment containing multiple lineages. Within the geographic area predicted to be suitable for B. anthracis by all ten best subset models, the A1.a sub-lineage was associated with a wider range of ecological tolerances than the outbreak-soil experiment. Analysis of rule types showed that logit rules predominate in the outbreak-soil experiment and range rules in the A1.a sub-lineage experiment. Random sub-setting of locality points suggests that models of B. anthracis distribution may be sensitive to sample size. Conclusions Our analysis supports careful consideration of the taxonomic resolution of data used to create ecological niche models. Further investigations into the environmental affinities of individual lineages and sub-lineages of B. anthracis will be useful in understanding the ecology of the disease at large and small scales. With model based predictions serving as approximations of disease risk, these efforts will improve the efficacy of public health interventions for anthrax prevention and control. PMID:22152056

SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development

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Rhys J.P. Skelton

2014-07-01

Full Text Available The study of human cardiogenesis would benefit from a detailed cell lineage fate map akin to that established for the haematopoietic lineages. Here we sought to define cell lineage relationships based on the expression of NKX2-5 and the cell surface markers VCAM1, SIRPA and CD34 during human cardiovascular development. Expression of NKX2-5GFP was used to identify cardiac progenitors and cardiomyocytes generated during the differentiation of NKX2-5GFP/w human embryonic stem cells (hESCs. Cardiovascular cell lineages sub-fractionated on the basis of SIRPA, VCAM1 and CD34 expression were assayed for differentiation potential and gene expression. The NKX2-5posCD34pos population gave rise to endothelial cells that rapidly lost NKX2-5 expression in culture. Conversely, NKX2-5 expression was maintained in myocardial committed cells, which progressed from being NKX2-5posSIRPApos to NKX2-5posSIRPAposVCAM1pos. Up-regulation of VCAM1 was accompanied by the expression of myofilament markers and reduced clonal capacity, implying a restriction of cell fate potential. Combinatorial expression of NKX2-5, SIRPA, VCAM1 and CD34 can be used to define discrete stages of cardiovascular cell lineage differentiation. These markers identify specific stages of cardiomyocyte and endothelial lineage commitment and, thus provide a scaffold for establishing a fate map of early human cardiogenesis.

How the Aridification of Australia Structured the Biogeography and Influenced the Diversification of a Large Lineage of Australian Cicadas.

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Owen, Christopher L; Marshall, David C; Hill, Kathy B R; Simon, Chris

2017-07-01

Over the last 30 million years, Australia's landscape has undergone dramatic cooling and drying due to the establishment of the Antarctic Circumpolar Current and change in global CO$_{2}$ levels. Studies have shown that many Australian organisms went extinct during these major cooling events, while others experienced adaptive radiations and increases in diversification rates as a result of exploiting new niches in the arid zone. Despite the many studies on diversification and biogeography in Australia, few have been continent-wide and none have focused on a group of organisms adapted to feeding on plants. We studied 162 species of cicadas in the Australian Pauropsalta complex, a large generic lineage within the tribe Cicadettini. We asked whether there were changes in the diversification rate of Pauropsalta over time and if so: 1) which clades were associated with the rate change? 2) did timing of rate shifts correspond to known periods of dramatic historical climate change, 3) did increases in diversification rate along select lineages correspond to adaptive radiations with movement into the arid zone? To address these questions, we estimated a molecular phylogeny of the Pauropsalta complex using ${\\sim}$5300 bp of nucleotide sequence data distributed among five loci (one mtDNA locus and four nDNA loci). We found that this large group of cicadas did not diversify at a constant rate as they spread through Australia; instead the signature of decreasing diversification rate changed roughly around the time of the expansion of the east Antarctic ice sheets ${\\sim}$16 Ma and the glaciation of the northern hemisphere ${\\sim}$3 Ma. Unlike other Australian taxa, the Pauropsalta complex did not explosively radiate in response to an early invasion of the arid zone. Instead multiple groups invaded the arid zone and experienced rates of diversification similar to mesic-distributed taxa. We found evidence for relictual groups, located in pre-Mesozoic habitat, that have not

A primitive Late Pliocene cheetah, and evolution of the cheetah lineage

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Christiansen, Per; Mazák, Ji H.

2009-01-01

The cheetah lineage is a group of large, slender, and long-limbed cats with a distinctive skull and dental morphology, of which only the extant cheetah (Acinonyx jubatus) is present today. The lineage is characterized by having abbreviated, tall, and domed crania, and a trenchant dentition with a much reduced, posteriorly placed protocone on the upper carnassial. In this article, we report on a new discovery of a Late Pliocene specimen from China with an estimated age of ≈2.2–2.5 million years, making it one of the oldest specimens known to date. A cladistic analysis confirmed that it is the most primitive cheetah known, and it shares a number of unambiguous derived cranial traits with the Acinonyx lineage, but has more primitive dentition than previously known cheetahs, demonstrating that the many unusual skull and dental characters hitherto considered characteristic of cheetahs evolved in a gradual fashion. Isolated teeth of primitive cheetahs may not be recognizable as such, but can be confused with, for instance, those of leopards or other similar-sized pantherine cats or pumas. The age and morphology of the new specimen supports an Old World origin of the cheetah lineage, not a New World one, as has been suggested. We name the new species Acinonyx kurteni in honor of the late Björn Kurtén. PMID:19114651

Lineage and the rights of cloned child in the islamic jurisprudence.

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Moeinifar, Mohaddeseh; Ardebeli, Faezeh Azimzadeh

2012-10-01

Lineage in the Islamic law is one of the most basic human rights each individual inherits from his family. When modern assisted reproductive technologies appeared in recent decades, the issue of lineage and the child's rights did not encounter serious challenges. But with the advent of these technologies, the issue of the child's lineage resulting from new technologies has become the center of attention. These technologies have a large share in the field of medicine. A new technique known as cloning has entered the realm of science and technology. Considering the possibility of the widespread use of this technique, the subject of cloned child's lineage and his/her rights would be one of the major issues related to this subject. In this paper, the authors have examined the various aspects of the subject and the opinions of theologians in this regard in order to present a best solution to this issue. In fact, the fundamental concern in this paper is to figure out the relationship between the cloned child, the cell donor, the egg donor and the owner of the uterus. In this paper, after considering the concepts of the parentage and identical twins' relationship would be explored and then a detailed analysis of the parental relationship and the Shiite jurisprudence scholars' opinion on these issues would be presented. Finally, the rights of cloned children would be taken into consideration.

A primitive Late Pliocene cheetah, and evolution of the cheetah lineage.

Science.gov (United States)

Christiansen, Per; Mazák, Ji H

2009-01-13

The cheetah lineage is a group of large, slender, and long-limbed cats with a distinctive skull and dental morphology, of which only the extant cheetah (Acinonyx jubatus) is present today. The lineage is characterized by having abbreviated, tall, and domed crania, and a trenchant dentition with a much reduced, posteriorly placed protocone on the upper carnassial. In this article, we report on a new discovery of a Late Pliocene specimen from China with an estimated age of approximately 2.2-2.5 million years, making it one of the oldest specimens known to date. A cladistic analysis confirmed that it is the most primitive cheetah known, and it shares a number of unambiguous derived cranial traits with the Acinonyx lineage, but has more primitive dentition than previously known cheetahs, demonstrating that the many unusual skull and dental characters hitherto considered characteristic of cheetahs evolved in a gradual fashion. Isolated teeth of primitive cheetahs may not be recognizable as such, but can be confused with, for instance, those of leopards or other similar-sized pantherine cats or pumas. The age and morphology of the new specimen supports an Old World origin of the cheetah lineage, not a New World one, as has been suggested. We name the new species Acinonyx kurteni in honor of the late Björn Kurtén.

Sympatric speciation: perfume preferences of orchid bee lineages.

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Jackson, Duncan E

2008-12-09

Female attraction to an environmentally derived mating signal released by male orchid bees may be tightly linked to shared olfactory preferences of both sexes. A change in perfume preference may have led to divergence of two morphologically distinct lineages.

Reading Mammal Diversity from Flies: The Persistence Period of Amplifiable Mammal mtDNA in Blowfly Guts (Chrysomya megacephala) and a New DNA Mini-Barcode Target

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Lee, Ping-Shin; Sing, Kong-Wah; Wilson, John-James

2015-01-01

Most tropical mammal species are threatened or data-deficient. Data collection is impeded by the traditional monitoring approaches which can be laborious, expensive and struggle to detect cryptic diversity. Monitoring approaches using mammal DNA derived from invertebrates are emerging as cost- and time-effective alternatives. As a step towards development of blowfly-derived DNA as an effective method for mammal monitoring in the biodiversity hotspot of Peninsular Malaysia, our objectives were (i) to determine the persistence period of amplifiable mammal mtDNA in blowfly guts through a laboratory feeding experiment (ii) to design and test primers that can selectively amplify mammal COI DNA mini-barcodes in the presence of high concentrations of blowfly DNA. The persistence period of amplifiable mammal mtDNA in blowfly guts was 24 h to 96 h post-feeding indicating the need for collecting flies within 24 h of capture to detect mammal mtDNA of sufficient quantity and quality. We designed a new primer combination for a COI DNA mini-barcode that did not amplify blowfly DNA and showed 89% amplification success for a dataset of mammals from Peninsular Malaysia. The short (205 bp) DNA mini-barcode could distinguish most mammal species (including separating dark taxa) and is of suitable length for high-throughput sequencing. Our new DNA mini-barcode target and a standardized trapping protocol with retrieval of blowflies every 24 h could point the way forward in the development of blowfly-derived DNA as an effective method for mammal monitoring. PMID:25898278

Reading Mammal Diversity from Flies: The Persistence Period of Amplifiable Mammal mtDNA in Blowfly Guts (Chrysomya megacephala and a New DNA Mini-Barcode Target.

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Ping-Shin Lee

Full Text Available Most tropical mammal species are threatened or data-deficient. Data collection is impeded by the traditional monitoring approaches which can be laborious, expensive and struggle to detect cryptic diversity. Monitoring approaches using mammal DNA derived from invertebrates are emerging as cost- and time-effective alternatives. As a step towards development of blowfly-derived DNA as an effective method for mammal monitoring in the biodiversity hotspot of Peninsular Malaysia, our objectives were (i to determine the persistence period of amplifiable mammal mtDNA in blowfly guts through a laboratory feeding experiment (ii to design and test primers that can selectively amplify mammal COI DNA mini-barcodes in the presence of high concentrations of blowfly DNA. The persistence period of amplifiable mammal mtDNA in blowfly guts was 24 h to 96 h post-feeding indicating the need for collecting flies within 24 h of capture to detect mammal mtDNA of sufficient quantity and quality. We designed a new primer combination for a COI DNA mini-barcode that did not amplify blowfly DNA and showed 89% amplification success for a dataset of mammals from Peninsular Malaysia. The short (205 bp DNA mini-barcode could distinguish most mammal species (including separating dark taxa and is of suitable length for high-throughput sequencing. Our new DNA mini-barcode target and a standardized trapping protocol with retrieval of blowflies every 24 h could point the way forward in the development of blowfly-derived DNA as an effective method for mammal monitoring.

Rapid and specific detection of Asian- and African-lineage Zika viruses.

Science.gov (United States)

Chotiwan, Nunya; Brewster, Connie D; Magalhaes, Tereza; Weger-Lucarelli, James; Duggal, Nisha K; Rückert, Claudia; Nguyen, Chilinh; Garcia Luna, Selene M; Fauver, Joseph R; Andre, Barb; Gray, Meg; Black, William C; Kading, Rebekah C; Ebel, Gregory D; Kuan, Guillermina; Balmaseda, Angel; Jaenisch, Thomas; Marques, Ernesto T A; Brault, Aaron C; Harris, Eva; Foy, Brian D; Quackenbush, Sandra L; Perera, Rushika; Rovnak, Joel

2017-05-03

Understanding the dynamics of Zika virus transmission and formulating rational strategies for its control require precise diagnostic tools that are also appropriate for resource-poor environments. We have developed a rapid and sensitive loop-mediated isothermal amplification (LAMP) assay that distinguishes Zika viruses of Asian and African lineages. The assay does not detect chikungunya virus or flaviviruses such as dengue, yellow fever, or West Nile viruses. The assay conditions allowed direct detection of Zika virus RNA in cultured infected cells; in mosquitoes; in virus-spiked samples of human blood, plasma, saliva, urine, and semen; and in infected patient serum, plasma, and semen samples without the need for RNA isolation or reverse transcription. The assay offers rapid, specific, sensitive, and inexpensive detection of the Asian-lineage Zika virus strain that is currently circulating in the Western hemisphere, and can also detect the African-lineage Zika virus strain using separate, specific primers. Copyright © 2017, American Association for the Advancement of Science.

Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging

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Hoi-Hung Cheung

2014-04-01

Full Text Available Werner syndrome (WS patients exhibit premature aging predominantly in mesenchyme-derived tissues, but not in neural lineages, a consequence of telomere dysfunction and accelerated senescence. The cause of this lineage-specific aging remains unknown. Here, we document that reprogramming of WS fibroblasts to pluripotency elongated telomere length and prevented telomere dysfunction. To obtain mechanistic insight into the origin of tissue-specific aging, we differentiated iPSCs to mesenchymal stem cells (MSCs and neural stem/progenitor cells (NPCs. We observed recurrence of premature senescence associated with accelerated telomere attrition and defective synthesis of the lagging strand telomeres in MSCs, but not in NPCs. We postulate this “aging” discrepancy is regulated by telomerase. Expression of hTERT or p53 knockdown ameliorated the accelerated aging phenotypein MSC, whereas inhibition of telomerase sensitized NPCs to DNA damage. Our findings unveil a role for telomerase in the protection of accelerated aging in a specific lineage of stem cells.

Rapid and specific detection of Asian- and African-lineage Zika viruses

Science.gov (United States)

Chotiwan, Nunya; Brewster, Connie D.; Magalhaes, Tereza; Weger-Lucarelli, James; Duggal, Nisha K.; Rückert, Claudia; Nguyen, Chilinh; Garcia Luna, Selene M.; Fauver, Joseph R.; Andre, Barb; Gray, Meg; Black, William C.; Kading, Rebekah C.; Ebel, Gregory D.; Kuan, Guillermina; Balmaseda, Angel; Jaenisch, Thomas; Marques, Ernesto T. A.; Brault, Aaron C.; Harris, Eva; Foy, Brian D.; Quackenbush, Sandra L.; Perera, Rushika; Rovnak, Joel

2017-01-01

Understanding the dynamics of Zika virus transmission and formulating rational strategies for its control require precise diagnostic tools that are also appropriate for resource-poor environments. We have developed a rapid and sensitive loop-mediated isothermal amplification (LAMP) assay that distinguishes Zika viruses of Asian and African lineages. The assay does not detect chikungunya virus or flaviviruses such as dengue, yellow fever, or West Nile viruses. The assay conditions allowed direct detection of Zika virus RNA in cultured infected cells; in mosquitoes; in virus-spiked samples of human blood, plasma, saliva, urine, and semen; and in infected patient serum, plasma, and semen samples without the need for RNA isolation or reverse transcription. The assay offers rapid, specific, sensitive, and inexpensive detection of the Asian-lineage Zika virus strain that is currently circulating in the Western hemisphere, and can also detect the African-lineage Zika virus strain using separate, specific primers. PMID:28469032

The rate and potential relevance of new mutations in a colonizing plant lineage.

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Moises Exposito-Alonso

2018-02-01

Full Text Available By following the evolution of populations that are initially genetically homogeneous, much can be learned about core biological principles. For example, it allows for detailed studies of the rate of emergence of de novo mutations and their change in frequency due to drift and selection. Unfortunately, in multicellular organisms with generation times of months or years, it is difficult to set up and carry out such experiments over many generations. An alternative is provided by "natural evolution experiments" that started from colonizations or invasions of new habitats by selfing lineages. With limited or missing gene flow from other lineages, new mutations and their effects can be easily detected. North America has been colonized in historic times by the plant Arabidopsis thaliana, and although multiple intercrossing lineages are found today, many of the individuals belong to a single lineage, HPG1. To determine in this lineage the rate of substitutions-the subset of mutations that survived natural selection and drift-, we have sequenced genomes from plants collected between 1863 and 2006. We identified 73 modern and 27 herbarium specimens that belonged to HPG1. Using the estimated substitution rate, we infer that the last common HPG1 ancestor lived in the early 17th century, when it was most likely introduced by chance from Europe. Mutations in coding regions are depleted in frequency compared to those in other portions of the genome, consistent with purifying selection. Nevertheless, a handful of mutations is found at high frequency in present-day populations. We link these to detectable phenotypic variance in traits of known ecological importance, life history and growth, which could reflect their adaptive value. Our work showcases how, by applying genomics methods to a combination of modern and historic samples from colonizing lineages, we can directly study new mutations and their potential evolutionary relevance.

Distinct lineages of Ebola virus in Guinea during the 2014 West African epidemic.

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Simon-Loriere, Etienne; Faye, Ousmane; Faye, Oumar; Koivogui, Lamine; Magassouba, Nfaly; Keita, Sakoba; Thiberge, Jean-Michel; Diancourt, Laure; Bouchier, Christiane; Vandenbogaert, Matthias; Caro, Valérie; Fall, Gamou; Buchmann, Jan P; Matranga, Christan B; Sabeti, Pardis C; Manuguerra, Jean-Claude; Holmes, Edward C; Sall, Amadou A

2015-08-06

An epidemic of Ebola virus disease of unprecedented scale has been ongoing for more than a year in West Africa. As of 29 April 2015, there have been 26,277 reported total cases (of which 14,895 have been laboratory confirmed) resulting in 10,899 deaths. The source of the outbreak was traced to the prefecture of Guéckédou in the forested region of southeastern Guinea. The virus later spread to the capital, Conakry, and to the neighbouring countries of Sierra Leone, Liberia, Nigeria, Senegal and Mali. In March 2014, when the first cases were detected in Conakry, the Institut Pasteur of Dakar, Senegal, deployed a mobile laboratory in Donka hospital to provide diagnostic services to the greater Conakry urban area and other regions of Guinea. Through this process we sampled 85 Ebola viruses (EBOV) from patients infected from July to November 2014, and report their full genome sequences here. Phylogenetic analysis reveals the sustained transmission of three distinct viral lineages co-circulating in Guinea, including the urban setting of Conakry and its surroundings. One lineage is unique to Guinea and closely related to the earliest sampled viruses of the epidemic. A second lineage contains viruses probably reintroduced from neighbouring Sierra Leone on multiple occasions, while a third lineage later spread from Guinea to Mali. Each lineage is defined by multiple mutations, including non-synonymous changes in the virion protein 35 (VP35), glycoprotein (GP) and RNA-dependent RNA polymerase (L) proteins. The viral GP is characterized by a glycosylation site modification and mutations in the mucin-like domain that could modify the outer shape of the virion. These data illustrate the ongoing ability of EBOV to develop lineage-specific and potentially phenotypically important variation.

Mutation of mtDNA ND1 Gene in 20 Type 2 Diabetes Mellitus Patients of Gorontalonese and Javanese Ethnicity

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AMIEN RAMADHAN ISHAK

2014-12-01

Full Text Available Mitochondrial gene mutation plays a role in the development of type two diabetes mellitus (T2DM. A point mutation in the mitochondrial gene Nicotinamide adenine dinucleotide dehydrogenase 1 (mtDNA ND1 gene mainly reported as the most common mutation related to T2DM. However, several studies have identified another SNP (single-nucleotide polymorphisms in the RNA region of mtDNA from patients from specific ethnic populations in Indonesia. Building on those findings, this study aimed to use PCR and DNA sequencing technology to identify nucleotides in RNA and ND1 fragment from 20 Gorontalonese and 20 Javanese T2DM patients, that may trigger T2DM expression. The results showed successful amplification of RNA along 294 bp for all samples. From these samples, we found two types of point mutation in Javanese patients in the G3316A and T3200C points of the rRNA and ND1 gene. In samples taken from Gorontalonese patients, no mutation were found in the RNA or ND1 region. We conclude that T2DM was triggered differently in our two populations. While genetic mutation is implicated for the 20 Javanese patients, T2DM pathogenesis in the Gorontalonese patients must be traced to other genetic, environmental, or behavioral factors.

Transcription factor expression uniquely identifies most postembryonic neuronal lineages in the Drosophila thoracic central nervous system.

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Lacin, Haluk; Zhu, Yi; Wilson, Beth A; Skeath, James B

2014-03-01

Most neurons of the adult Drosophila ventral nerve cord arise from a burst of neurogenesis during the third larval instar stage. Most of this growth occurs in thoracic neuromeres, which contain 25 individually identifiable postembryonic neuronal lineages. Initially, each lineage consists of two hemilineages--'A' (Notch(On)) and 'B' (Notch(Off))--that exhibit distinct axonal trajectories or fates. No reliable method presently exists to identify these lineages or hemilineages unambiguously other than labor-intensive lineage-tracing methods. By combining mosaic analysis with a repressible cell marker (MARCM) analysis with gene expression studies, we constructed a gene expression map that enables the rapid, unambiguous identification of 23 of the 25 postembryonic lineages based on the expression of 15 transcription factors. Pilot genetic studies reveal that these transcription factors regulate the specification and differentiation of postembryonic neurons: for example, Nkx6 is necessary and sufficient to direct axonal pathway selection in lineage 3. The gene expression map thus provides a descriptive foundation for the genetic and molecular dissection of adult-specific neurogenesis and identifies many transcription factors that are likely to regulate the development and differentiation of discrete subsets of postembryonic neurons.

Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A

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Wang Huawei [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)]|[Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming 650091 (China); Jia Xiaoyun; Ji Yanli [State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060 (China); Kong Qingpeng [State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223 (China); Zhang Qingjiong [State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060 (China)], E-mail: qingjiongzhang@yahoo.com; Yao Yonggang [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)]|[State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223 (China)], E-mail: ygyaozh@yahoo.com; Zhang Yaping [Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming 650091 (China)]|[State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223 (China)

2008-08-25

The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P < 0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate any putatively pathogenic mutation that cosegregated with G11778A in these two pedigrees. Our results suggest that the variable penetrance of LHON in the two Chinese families is independent of both their mtDNA haplotype background and a secondary mutation G13708A. As a result, it is likely that unknown nuclear gene involvement and/or other factors contribute to the strikingly different penetrance of LHON.

Phylogeography of the Koala, (Phascolarctos cinereus), and Harmonising Data to Inform Conservation

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Neaves, Linda E.; Frankham, Greta J.; Dennison, Siobhan; FitzGibbon, Sean; Flannagan, Cheyne; Gillett, Amber; Hynes, Emily; Handasyde, Kathrine; Helgen, Kristofer M.; Tsangaras, Kyriakos; Greenwood, Alex D.; Eldridge, Mark D. B.; Johnson, Rebecca N.

2016-01-01

The Australian continent exhibits complex biogeographic patterns but studies of the impacts of Pleistocene climatic oscillation on the mesic environments of the Southern Hemisphere are limited. The koala (Phascolarctos cinereus), one of Australia’s most iconic species, was historically widely distributed throughout much of eastern Australia but currently represents a complex conservation challenge. To better understand the challenges to koala genetic health, we assessed the phylogeographic history of the koala. Variation in the maternally inherited mitochondrial DNA (mtDNA) Control Region (CR) was examined in 662 koalas sampled throughout their distribution. In addition, koala CR haplotypes accessioned to Genbank were evaluated and consolidated. A total of 53 unique CR haplotypes have been isolated from koalas to date (including 15 haplotypes novel to this study). The relationships among koala CR haplotypes were indicative of a single Evolutionary Significant Unit and do not support the recognition of subspecies, but were separated into four weakly differentiated lineages which correspond to three geographic clusters: a central lineage, a southern lineage and two northern lineages co-occurring north of Brisbane. The three geographic clusters were separated by known Pleistocene biogeographic barriers: the Brisbane River Valley and Clarence River Valley, although there was evidence of mixing amongst clusters. While there is evidence for historical connectivity, current koala populations exhibit greater structure, suggesting habitat fragmentation may have restricted female-mediated gene flow. Since mtDNA data informs conservation planning, we provide a summary of existing CR haplotypes, standardise nomenclature and make recommendations for future studies to harmonise existing datasets. This holistic approach is critical to ensuring management is effective and small scale local population studies can be integrated into a wider species context. PMID:27588685

Phylogeography of the West Indian manatee (Trichechus manatus): how many populations and how many taxa?

Science.gov (United States)

Garcia-Rodriguez, A I; Bowen, B W; Domning, D; Mignucci-Giannoni, A; Marmontel, M; Montoya-Ospina, A; Morales-Vela, B; Rudin, M; Bonde, R K; McGuire, P M

1998-09-01

To resolve the population genetic structure and phylogeography of the West Indian manatee (Trichechus manatus), mitochondrial (mt) DNA control region sequences were compared among eight locations across the western Atlantic region. Fifteen haplotypes were identified among 86 individuals from Florida, Puerto Rico, the Dominican Republic, Mexico, Columbia, Venezuela, Guyana and Brazil. Despite the manatee's ability to move thousands of kilometers along continental margins, strong population separations between most locations were demonstrated with significant haplotype frequency shifts. These findings are consistent with tagging studies which indicate that stretches of open water and unsuitable coastal habitats constitute substantial barriers to gene flow and colonization. Low levels of genetic diversity within Florida and Brazilian samples might be explained by recent colonization into high latitudes or bottleneck effects. Three distinctive mtDNA lineages were observed in an intraspecific phylogeny of T. manatus, corresponding approximately to: (i) Florida and the West Indies; (ii) the Gulf of Mexico to the Caribbean rivers of South America; and (iii) the northeast Atlantic coast of South America. These lineages, which are not concordant with previous subspecies designations, are separated by sequence divergence estimates of d = 0.04-0.07, approximately the same level of divergence observed between T. manatus and the Amazonian manatee (T. inunguis, n = 16). Three individuals from Guyana, identified as T. manatus, had mtDNA haplotypes which are affiliated with the endemic Amazon form T. inunguis. The three primary T. manatus lineages and the T. inunguis lineage may represent relatively deep phylogeographic partitions which have been bridged recently due to changes in habitat availability (after the Wisconsin glacial period, 10 000 B P), natural colonization, and human-mediated transplantation.

Phylogeography of the West Indian manatee (Trichechus manatus): How many populations and how many taxa?

Science.gov (United States)

Garcia-Rodriguez, A. I.; Bowen, B.W.; Domning, D.; Mignucci-Giannoni, A. A.; Marmontel, M.; Montoya-Ospina, R. A.; Morales-Vela, B.; Rudin, M.; Bonde, R.K.; McGuire, P.M.

1998-01-01

To resolve the population genetic structure and phylogeography of the West Indian manatee (Trichechus manatus), mitochondrial (mt) DNA control region sequences were compared among eight locations across the western Atlantic region. Fifteen haplotypes were identified among 86 individuals from Florida, Puerto Rico, the Dominican Republic, Mexico, Colombia, Venezuela, Guyana and Brazil. Despite the manatee's ability to move thousands of kilometres along continental margins, strong population separations between most locations were demonstrated with significant haplotype frequency shifts. These findings are consistent with tagging studies which indicate that stretches of open water and unsuitable coastal habitats constitute substantial barriers to gene flow and colonization. Low levels of genetic diversity within Florida and Brazilian samples might be explained by recent colonization into high latitudes or bottleneck effects. Three distinctive mtDNA lineages were observed in an intraspecific phylogeny of T. manatus, corresponding approximately to: (i) Florida and the West Indies; (ii) the Gulf of Mexico to the Caribbean rivers of South America; and (iii) the northeast Atlantic coast of South America. These lineages, which are not concordant with previous subspecies designations, are separated by sequence divergence estimates of d = 0.04-0.07, approximately the same level of divergence observed between T. manatus and the Amazonian manatee (T. inunguis, n = 16). Three individuals from Guyana, identified as T. manatus, had mtDNA haplotypes which are affiliated with the endemic Amazon form T. inunguis. The three primary T. manatus lineages and the T. inunguis lineage may represent relatively deep phylogeographic partitions which have been bridged recently due to changes in habitat availability (after the Wisconsin glacial period, 10 000 BP), natural colonization, and human-mediated transplantation.

Phylogeography of the Koala, (Phascolarctos cinereus, and Harmonising Data to Inform Conservation.

Directory of Open Access Journals (Sweden)

Linda E Neaves

Full Text Available The Australian continent exhibits complex biogeographic patterns but studies of the impacts of Pleistocene climatic oscillation on the mesic environments of the Southern Hemisphere are limited. The koala (Phascolarctos cinereus, one of Australia's most iconic species, was historically widely distributed throughout much of eastern Australia but currently represents a complex conservation challenge. To better understand the challenges to koala genetic health, we assessed the phylogeographic history of the koala. Variation in the maternally inherited mitochondrial DNA (mtDNA Control Region (CR was examined in 662 koalas sampled throughout their distribution. In addition, koala CR haplotypes accessioned to Genbank were evaluated and consolidated. A total of 53 unique CR haplotypes have been isolated from koalas to date (including 15 haplotypes novel to this study. The relationships among koala CR haplotypes were indicative of a single Evolutionary Significant Unit and do not support the recognition of subspecies, but were separated into four weakly differentiated lineages which correspond to three geographic clusters: a central lineage, a southern lineage and two northern lineages co-occurring north of Brisbane. The three geographic clusters were separated by known Pleistocene biogeographic barriers: the Brisbane River Valley and Clarence River Valley, although there was evidence of mixing amongst clusters. While there is evidence for historical connectivity, current koala populations exhibit greater structure, suggesting habitat fragmentation may have restricted female-mediated gene flow. Since mtDNA data informs conservation planning, we provide a summary of existing CR haplotypes, standardise nomenclature and make recommendations for future studies to harmonise existing datasets. This holistic approach is critical to ensuring management is effective and small scale local population studies can be integrated into a wider species context.

Phylogeography of the Koala, (Phascolarctos cinereus), and Harmonising Data to Inform Conservation.

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Neaves, Linda E; Frankham, Greta J; Dennison, Siobhan; FitzGibbon, Sean; Flannagan, Cheyne; Gillett, Amber; Hynes, Emily; Handasyde, Kathrine; Helgen, Kristofer M; Tsangaras, Kyriakos; Greenwood, Alex D; Eldridge, Mark D B; Johnson, Rebecca N

2016-01-01

The Australian continent exhibits complex biogeographic patterns but studies of the impacts of Pleistocene climatic oscillation on the mesic environments of the Southern Hemisphere are limited. The koala (Phascolarctos cinereus), one of Australia's most iconic species, was historically widely distributed throughout much of eastern Australia but currently represents a complex conservation challenge. To better understand the challenges to koala genetic health, we assessed the phylogeographic history of the koala. Variation in the maternally inherited mitochondrial DNA (mtDNA) Control Region (CR) was examined in 662 koalas sampled throughout their distribution. In addition, koala CR haplotypes accessioned to Genbank were evaluated and consolidated. A total of 53 unique CR haplotypes have been isolated from koalas to date (including 15 haplotypes novel to this study). The relationships among koala CR haplotypes were indicative of a single Evolutionary Significant Unit and do not support the recognition of subspecies, but were separated into four weakly differentiated lineages which correspond to three geographic clusters: a central lineage, a southern lineage and two northern lineages co-occurring north of Brisbane. The three geographic clusters were separated by known Pleistocene biogeographic barriers: the Brisbane River Valley and Clarence River Valley, although there was evidence of mixing amongst clusters. While there is evidence for historical connectivity, current koala populations exhibit greater structure, suggesting habitat fragmentation may have restricted female-mediated gene flow. Since mtDNA data informs conservation planning, we provide a summary of existing CR haplotypes, standardise nomenclature and make recommendations for future studies to harmonise existing datasets. This holistic approach is critical to ensuring management is effective and small scale local population studies can be integrated into a wider species context.

Mitochondrial DNA haplogroup phylogeny of the dog: Proposal for a cladistic nomenclature.

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Fregel, Rosa; Suárez, Nicolás M; Betancor, Eva; González, Ana M; Cabrera, Vicente M; Pestano, José

2015-05-01

Canis lupus familiaris mitochondrial DNA analysis has increased in recent years, not only for the purpose of deciphering dog domestication but also for forensic genetic studies or breed characterization. The resultant accumulation of data has increased the need for a normalized and phylogenetic-based nomenclature like those provided for human maternal lineages. Although a standardized classification has been proposed, haplotype names within clades have been assigned gradually without considering the evolutionary history of dog mtDNA. Moreover, this classification is based only on the D-loop region, proven to be insufficient for phylogenetic purposes due to its high number of recurrent mutations and the lack of relevant information present in the coding region. In this study, we design 1) a refined mtDNA cladistic nomenclature from a phylogenetic tree based on complete sequences, classifying dog maternal lineages into haplogroups defined by specific diagnostic mutations, and 2) a coding region SNP analysis that allows a more accurate classification into haplogroups when combined with D-loop sequencing, thus improving the phylogenetic information obtained in dog mitochondrial DNA studies. Copyright © 2015 Elsevier B.V. All rights reserved.

Mitochondrial phylogeny and biogeographic history of the Greek endemic land-snail genus Codringtonia Kobelt 1898 (Gastropoda, Pulmonata, Helicidae).

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Kotsakiozi, Panayiota; Parmakelis, Aristeidis; Giokas, Sinos; Papanikolaou, Irene; Valakos, Efstratios D

2012-02-01

The aim of this work was to infer the phylogeny of the Greek endemic land-snail genus Codringtonia Kobelt 1898, estimate the time frame of the radiation of the genus, and propose a biogeographic scenario that could explain the contemporary distribution of Codringtonia lineages. The study took place in the districts of Peloponnese, Central Greece and Epirus of mainland Greece. Sequence data originating from three mtDNA genes (COI, COII, and 16S rDNA) were used to infer the phylogeny of the eight nominal Codringtonia species. Furthermore, the radiation time-frame of extant Codringtonia species was estimated using a relaxed molecular clock analysis and mtDNA substitution rates of land snails. The phylogenetic analysis supported the existence of six Codringtonia lineages in Greece and indicated that one nominal species (Codringtonia neocrassa) might belong to a separate genus distantly related to Codringtonia. The time frame of differentiation of Codringtonia species was placed in the Late Miocene-Pleistocene epoch. The dispersal-vicariance analysis performed indicated that most probably Codringtonia exhibited a north-to-south spread with the ancestral area being that of central Greek mainland, accompanied with duplication (speciation) and vicariance events. Copyright © 2011 Elsevier Inc. All rights reserved.

Constrained body shape among highly genetically divergent allopatric lineages of the supralittoral isopod Ligia occidentalis (Oniscidea).

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Santamaria, Carlos A; Mateos, Mariana; DeWitt, Thomas J; Hurtado, Luis A

2016-03-01

Multiple highly divergent lineages have been identified within Ligia occidentalis sensu lato, a rocky supralittoral isopod distributed along a ~3000 km latitudinal gradient that encompasses several proposed marine biogeographic provinces and ecoregions in the eastern Pacific. Highly divergent lineages have nonoverlapping geographic distributions, with distributional limits that generally correspond with sharp environmental changes. Crossbreeding experiments suggest postmating reproductive barriers exist among some of them, and surveys of mitochondrial and nuclear gene markers do not show evidence of hybridization. Populations are highly isolated, some of which appear to be very small; thus, the effects of drift are expected to reduce the efficiency of selection. Large genetic divergences among lineages, marked environmental differences in their ranges, reproductive isolation, and/or high isolation of populations may have resulted in morphological differences in L. occidentalis, not detected yet by traditional taxonomy. We used landmark-based geometric morphometric analyses to test for differences in body shape among highly divergent lineages of L. occidentalis, and among populations within these lineages. We analyzed a total of 492 individuals from 53 coastal localities from the southern California Bight to Central Mexico, including the Gulf of California. We conducted discriminant function analyses (DFAs) on body shape morphometrics to assess morphological variation among genetically differentiated lineages and their populations. We also tested for associations between phylogeny and morphological variation, and whether genetic divergence is correlated to multivariate morphological divergence. We detected significant differences in body shape among highly divergent lineages, and among populations within these lineages. Nonetheless, neither lineages nor populations can be discriminated on the basis of body shape, because correct classification rates of cross

Persistence of the single lineage of transmissible 'social cancer' in an asexual ant.

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Dobata, S; Sasaki, T; Mori, H; Hasegawa, E; Shimada, M; Tsuji, K

2011-02-01

How cooperation can arise and persist, given the threat of cheating phenotypes, is a central problem in evolutionary biology, but the actual significance of cheating in natural populations is still poorly understood. Theories of social evolution predict that cheater lineages are evolutionarily short-lived. However, an exception comes from obligate socially parasitic species, some of which thought to have arisen as cheaters within cooperator colonies and then diverged through sympatric speciation. This process requires the cheater lineage to persist by avoiding rapid extinction that would result from the fact that the cheaters inflict fitness cost on their host. We examined whether this prerequisite is fulfilled, by estimating the persistence time of cheaters in a field population of the parthenogenetic ant Pristomyrmex punctatus. Population genetic analysis found that the cheaters belong to one monophyletic lineage which we infer has persisted for 200-9200 generations. We show that the cheaters migrate and are thus horizontally transmitted between colonies, a trait allowing the lineage to avoid rapid extinction with its host colony. Although horizontal transmission of disruptive cheaters has the potential to induce extinction of the entire population, such collapse is likely averted when there is spatially restricted migration in a structured population, a scenario that matches the observed isolation by distance pattern that we found. We compare our result with other examples of disruptive and horizontally transmissible cheater lineages in nature. © 2010 Blackwell Publishing Ltd.

Unique mitochondrial DNA lineages in Irish stickleback populations: cryptic refugium or rapid recolonization?

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Ravinet, Mark; Harrod, Chris; Eizaguirre, Christophe; Prodöhl, Paulo A

2014-06-01

Repeated recolonization of freshwater environments following Pleistocene glaciations has played a major role in the evolution and adaptation of anadromous taxa. Located at the western fringe of Europe, Ireland and Britain were likely recolonized rapidly by anadromous fishes from the North Atlantic following the last glacial maximum (LGM). While the presence of unique mitochondrial haplotypes in Ireland suggests that a cryptic northern refugium may have played a role in recolonization, no explicit test of this hypothesis has been conducted. The three-spined stickleback is native and ubiquitous to aquatic ecosystems throughout Ireland, making it an excellent model species with which to examine the biogeographical history of anadromous fishes in the region. We used mitochondrial and microsatellite markers to examine the presence of divergent evolutionary lineages and to assess broad-scale patterns of geographical clustering among postglacially isolated populations. Our results confirm that Ireland is a region of secondary contact for divergent mitochondrial lineages and that endemic haplotypes occur in populations in Central and Southern Ireland. To test whether a putative Irish lineage arose from a cryptic Irish refugium, we used approximate Bayesian computation (ABC). However, we found no support for this hypothesis. Instead, the Irish lineage likely diverged from the European lineage as a result of postglacial isolation of freshwater populations by rising sea levels. These findings emphasize the need to rigorously test biogeographical hypothesis and contribute further evidence that postglacial processes may have shaped genetic diversity in temperate fauna.

Colon stem cell and crypt dynamics exposed by cell lineage reconstruction.

Directory of Open Access Journals (Sweden)

Yitzhak Reizel

2011-07-01

Full Text Available Stem cell dynamics in vivo are often being studied by lineage tracing methods. Our laboratory has previously developed a retrospective method for reconstructing cell lineage trees from somatic mutations accumulated in microsatellites. This method was applied here to explore different aspects of stem cell dynamics in the mouse colon without the use of stem cell markers. We first demonstrated the reliability of our method for the study of stem cells by confirming previously established facts, and then we addressed open questions. Our findings confirmed that colon crypts are monoclonal and that, throughout adulthood, the process of monoclonal conversion plays a major role in the maintenance of crypts. The absence of immortal strand mechanism in crypts stem cells was validated by the age-dependent accumulation of microsatellite mutations. In addition, we confirmed the positive correlation between physical and lineage proximity of crypts, by showing that the colon is separated into small domains that share a common ancestor. We gained new data demonstrating that colon epithelium is clustered separately from hematopoietic and other cell types, indicating that the colon is constituted of few progenitors and ruling out significant renewal of colonic epithelium from hematopoietic cells during adulthood. Overall, our study demonstrates the reliability of cell lineage reconstruction for the study of stem cell dynamics, and it further addresses open questions in colon stem cells. In addition, this method can be applied to study stem cell dynamics in other systems.

Evidence of ancient DNA reveals the first European lineage in Iron Age Central China.

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Xie, C Z; Li, C X; Cui, Y Q; Zhang, Q C; Fu, Y Q; Zhu, H; Zhou, H

2007-07-07

Various studies on ancient DNA have attempted to reconstruct population movement in Asia, with much interest focused on determining the arrival of European lineages in ancient East Asia. Here, we discuss our analysis of the mitochondrial DNA of human remains excavated from the Yu Hong tomb in Taiyuan, China, dated 1400 years ago. The burial style of this tomb is characteristic of Central Asia at that time. Our analysis shows that Yu Hong belonged to the haplogroup U5, one of the oldest western Eurasian-specific haplogroups, while his wife can be classified as haplogroup G, the type prevalent in East Asia. Our findings show that this man with European lineage arrived in Taiyuan approximately 1400 years ago, and most probably married a local woman. Haplogroup U5 was the first west Eurasian-specific lineage to be found in the central part of ancient China, and Taiyuan may be the easternmost location of the discovered remains of European lineage in ancient China.

Multi-locus estimates of population structure and migration in a fence lizard hybrid zone.

Directory of Open Access Journals (Sweden)

Adam D Leaché

Full Text Available A hybrid zone between two species of lizards in the genus Sceloporus (S. cowlesi and S. tristichus on the Mogollon Rim in Arizona provides a unique opportunity to study the processes of lineage divergence and merging. This hybrid zone involves complex interactions between 2 morphologically and ecologically divergent subspecies, 3 chromosomal groups, and 4 mitochondrial DNA (mtDNA clades. The spatial patterns of divergence between morphology, chromosomes and mtDNA are discordant, and determining which of these character types (if any reflects the underlying population-level lineages that are of interest has remained impeded by character conflict. The focus of this study is to estimate the number of populations interacting in the hybrid zone using multi-locus nuclear data, and to then estimate the migration rates and divergence time between the inferred populations. Multi-locus estimates of population structure and gene flow were obtained from 12 anonymous nuclear loci sequenced for 93 specimens of Sceloporus. Population structure estimates support two populations, and this result is robust to changes to the prior probability distribution used in the Bayesian analysis and the use of spatially-explicit or non-spatial models. A coalescent analysis of population divergence suggests that gene flow is high between the two populations, and that the timing of divergence is restricted to the Pleistocene. The hybrid zone is more accurately described as involving two populations belonging to S. tristichus, and the presence of S. cowlesi mtDNA haplotypes in the hybrid zone is an anomaly resulting from mitochondrial introgression.

ACCELERATED EVOLUTION OF LAND SNAILS MANDARINA IN THE OCEANIC BONIN ISLANDS: EVIDENCE FROM MITOCHONDRIAL DNA SEQUENCES.

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Chiba, Satoshi

1999-04-01

An endemic land snail genus Mandarina of the oceanic Bonin (Ogasawara) Islands shows exceptionally rapid evolution not only of morphological and ecological traits, but of DNA sequence. A phylogenetic relationship based on mitochondrial DNA (mtDNA) sequences suggests that morphological differences equivalent to the differences between families were produced between Mandarina and its ancestor during the Pleistocene. The inferred phylogeny shows that species with similar morphologies and life habitats appeared repeatedly and independently in different lineages and islands at different times. Sequential adaptive radiations occurred in different islands of the Bonin Islands and species occupying arboreal, semiarboreal, and terrestrial habitat arose independently in each island. Because of a close relationship between shell morphology and life habitat, independent evolution of the same life habitat in different islands created species possesing the same shell morphology in different islands and lineages. This rapid evolution produced some incongruences between phylogenetic relationship and species taxonomy. Levels of sequence divergence of mtDNA among the species of Mandarina is extremely high. The maximum level of sequence divergence at 16S and 12S ribosomal RNA sequence within Mandarina are 18.7% and 17.7%, respectively, and this suggests that evolution of mtDNA of Mandarina is extremely rapid, more than 20 times faster than the standard rate in other animals. The present examination reveals that evolution of morphological and ecological traits occurs at extremely high rates in the time of adaptive radiation, especially in fragmented environments. © 1999 The Society for the Study of Evolution.

Involvement of multiple cell lineages in atherogenesis | Ogeng'o ...

African Journals Online (AJOL)

Involvement of multiple cell lineages in atherogenesis. ... mast cells, dendritic cells, macrophages and immigrant cells usually found in blood, namely ... which influence inflammation, migration, proliferation and secretory activity of each other in ...

Bridging the gap between postembryonic cell lineages and identified embryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster

Directory of Open Access Journals (Sweden)

Oliver Birkholz

2015-03-01

Full Text Available The clarification of complete cell lineages, which are produced by specific stem cells, is fundamental for understanding mechanisms, controlling the generation of cell diversity and patterning in an emerging tissue. In the developing Central Nervous System (CNS of Drosophila, neural stem cells (neuroblasts exhibit two periods of proliferation: During embryogenesis they produce primary lineages, which form the larval CNS. After a phase of mitotic quiescence, a subpopulation of them resumes proliferation in the larva to give rise to secondary lineages that build up the CNS of the adult fly. Within the ventral nerve cord (VNC detailed descriptions exist for both primary and secondary lineages. However, while primary lineages have been linked to identified neuroblasts, the assignment of secondary lineages has so far been hampered by technical limitations. Therefore, primary and secondary neural lineages co-existed as isolated model systems. Here we provide the missing link between the two systems for all lineages in the thoracic and abdominal neuromeres. Using the Flybow technique, embryonic neuroblasts were identified by their characteristic and unique lineages in the living embryo and their further development was traced into the late larval stage. This comprehensive analysis provides the first complete view of which embryonic neuroblasts are postembryonically reactivated along the anterior/posterior-axis of the VNC, and reveals the relationship between projection patterns of primary and secondary sublineages.

Sequence polymorphism data of the hypervariable regions of mitochondrial DNA in the Yadav population of Haryana.

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Verma, Kapil; Sharma, Sapna; Sharma, Arun; Dalal, Jyoti; Bhardwaj, Tapeshwar

2018-06-01

Genetic variations among humans occur both within and among populations and range from single nucleotide changes to multiple-nucleotide variants. These multiple-nucleotide variants are useful for studying the relationships among individuals or various population groups. The study of human genetic variations can help scientists understand how different population groups are biologically related to one another. Sequence analysis of hypervariable regions of human mitochondrial DNA (mtDNA) has been successfully used for the genetic characterization of different population groups for forensic purposes. It is well established that different ethnic or population groups differ significantly in their mtDNA distributions. In the last decade, very little research has been conducted on mtDNA variations in the Indian population, although such data would be useful for elucidating the history of human population expansion across the world. Moreover, forensic studies on mtDNA variations in the Indian subcontinent are also scarce, particularly in the northern part of India. In this report, variations in the hypervariable regions of mtDNA were analyzed in the Yadav population of Haryana. Different molecular diversity indices were computed. Further, the obtained haplotypes were classified into different haplogroups and the phylogenetic relationship between different haplogroups was inferred.

Comparison of Cytotoxic Activity in Leukemic Lineages Reveals Important Features of β-Hairpin Antimicrobial Peptides.

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Buri, Marcus V; Torquato, Heron F Vieira; Barros, Carlos Castilho; Ide, Jaime S; Miranda, Antonio; Paredes-Gamero, Edgar J

2017-07-01

Several reports described different modes of cell death triggered by antimicrobial peptides (AMPs) due to direct effects on membrane disruption, and more recently by apoptosis and necrosis-like patterns. Cytotoxic curves of four β-hairpin AMPs (gomesin, protegrin, tachyplesin, and polyphemusin) were obtained from several human leukemic lineages and normal monocytes and Two cell lines were then selected based on their cytotoxic sensitivity. One was sensitive to AMPs (K562) and the other resistant (KG-1) and their effect compared between these lineages. Thus, these lineages were chosen to further investigate biological features related with their cytotoxicities to AMPs. Stimulation with AMPs produced cell death, with activation of caspase-3, in K562 lineage. Increase on the fluidity of plasmatic membrane by reducing cholesterol potentiated cytotoxicity of AMPs in both lineages. Quantification of internal and external gomesin binding to the cellular membrane of both K562 and KG-1 cells showed that more peptide is accumulated inside of K562 cells. Additionally, evaluation of multi-drug resistant pumps activity showed that KG-1 has more activity than K562 lineage. A comparison of intrinsic gene patterns showed great differences between K562 and KG-1, but stimulation with gomesin promoted few changes in gene expression patterns. Differences in internalization process through the plasma membrane, multidrug resistance pumps activity, and gene expression pattern are important features to AMPs regulated cell death. J. Cell. Biochem. 118: 1764-1773, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Autosomal and uniparental portraits of the native populations of Sakha (Yakutia): implications for the peopling of Northeast Eurasia.

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Fedorova, Sardana A; Reidla, Maere; Metspalu, Ene; Metspalu, Mait; Rootsi, Siiri; Tambets, Kristiina; Trofimova, Natalya; Zhadanov, Sergey I; Hooshiar Kashani, Baharak; Olivieri, Anna; Voevoda, Mikhail I; Osipova, Ludmila P; Platonov, Fedor A; Tomsky, Mikhail I; Khusnutdinova, Elza K; Torroni, Antonio; Villems, Richard

2013-06-19

Sakha--an area connecting South and Northeast Siberia--is significant for understanding the history of peopling of Northeast Eurasia and the Americas. Previous studies have shown a genetic contiguity between Siberia and East Asia and the key role of South Siberia in the colonization of Siberia. We report the results of a high-resolution phylogenetic analysis of 701 mtDNAs and 318 Y chromosomes from five native populations of Sakha (Yakuts, Evenks, Evens, Yukaghirs and Dolgans) and of the analysis of more than 500,000 autosomal SNPs of 758 individuals from 55 populations, including 40 previously unpublished samples from Siberia. Phylogenetically terminal clades of East Asian mtDNA haplogroups C and D and Y-chromosome haplogroups N1c, N1b and C3, constituting the core of the gene pool of the native populations from Sakha, connect Sakha and South Siberia. Analysis of autosomal SNP data confirms the genetic continuity between Sakha and South Siberia. Maternal lineages D5a2a2, C4a1c, C4a2, C5b1b and the Yakut-specific STR sub-clade of Y-chromosome haplogroup N1c can be linked to a migration of Yakut ancestors, while the paternal lineage C3c was most likely carried to Sakha by the expansion of the Tungusic people. MtDNA haplogroups Z1a1b and Z1a3, present in Yukaghirs, Evens and Dolgans, show traces of different and probably more ancient migration(s). Analysis of both haploid loci and autosomal SNP data revealed only minor genetic components shared between Sakha and the extreme Northeast Siberia. Although the major part of West Eurasian maternal and paternal lineages in Sakha could originate from recent admixture with East Europeans, mtDNA haplogroups H8, H20a and HV1a1a, as well as Y-chromosome haplogroup J, more probably reflect an ancient gene flow from West Eurasia through Central Asia and South Siberia. Our high-resolution phylogenetic dissection of mtDNA and Y-chromosome haplogroups as well as analysis of autosomal SNP data suggests that Sakha was colonized by

Molecular phylogenetics of the family Cyprinidae (Actinopterygii: Cypriniformes) as evidenced by sequence variation in the first intron of S7 ribosomal protein-coding gene: further evidence from a nuclear gene of the systematic chaos in the family.

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He, Shunping; Mayden, Richard L; Wang, Xuzheng; Wang, Wei; Tang, Kevin L; Chen, Wei-Jen; Chen, Yiyu

2008-03-01

The family Cyprinidae is the largest freshwater fish group in the world, including over 200 genera and 2100 species. The phylogenetic relationships of major clades within this family are simply poorly understood, largely because of the overwhelming diversity of the group; however, several investigators have advanced different hypotheses of relationships that pre- and post-date the use of shared-derived characters as advocated through phylogenetic systematics. As expected, most previous investigations used morphological characters. Recently, mitochondrial DNA (mtDNA) sequences and combined morphological and mtDNA investigations have been used to explore and advance our understanding of species relationships and test monophyletic groupings. Limitations of these studies include limited taxon sampling and a strict reliance upon maternally inherited mtDNA variation. The present study is the first endeavor to recover the phylogenetic relationships of the 12 previously recognized monophyletic subfamilies within the Cyprinidae using newly sequenced nuclear DNA (nDNA) for over 50 species representing members of the different previously hypothesized subfamily and family groupings within the Cyprinidae and from other cypriniform families as outgroup taxa. Hypothesized phylogenetic relationships are constructed using maximum parsimony and Basyesian analyses of 1042 sites, of which 971 sites were variable and 790 were phylogenetically informative. Using other appropriate cypriniform taxa of the families Catostomidae (Myxocyprinus asiaticus), Gyrinocheilidae (Gyrinocheilus aymonieri), and Balitoridae (Nemacheilus sp. and Beaufortia kweichowensis) as outgroups, the Cyprinidae is resolved as a monophyletic group. Within the family the genera Raiamas, Barilius, Danio, and Rasbora, representing many of the tropical cyprinids, represent basal members of the family. All other species can be classified into variably supported and resolved monophyletic lineages, depending upon analysis

A Predominantly Neolithic Origin for European Paternal Lineages

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Balaresque, Patricia; Bowden, Georgina R.; Adams, Susan M.; Leung, Ho-Yee; King, Turi E.; Rosser, Zoë H.; Goodwin, Jane; Moisan, Jean-Paul; Richard, Christelle; Millward, Ann; Demaine, Andrew G.; Barbujani, Guido; Previderè, Carlo; Wilson, Ian J.; Tyler-Smith, Chris; Jobling, Mark A.

2010-01-01

The relative contributions to modern European populations of Paleolithic hunter-gatherers and Neolithic farmers from the Near East have been intensely debated. Haplogroup R1b1b2 (R-M269) is the commonest European Y-chromosomal lineage, increasing in frequency from east to west, and carried by 110 million European men. Previous studies suggested a Paleolithic origin, but here we show that the geographical distribution of its microsatellite diversity is best explained by spread from a single source in the Near East via Anatolia during the Neolithic. Taken with evidence on the origins of other haplogroups, this indicates that most European Y chromosomes originate in the Neolithic expansion. This reinterpretation makes Europe a prime example of how technological and cultural change is linked with the expansion of a Y-chromosomal lineage, and the contrast of this pattern with that shown by maternally inherited mitochondrial DNA suggests a unique role for males in the transition. PMID:20087410

Metabolomic elucidation of pork from different crossbreds

DEFF Research Database (Denmark)

Bertram, Hanne Christine S.; Straadt, Ida Krestine; Clausen, Morten Rahr

, and correlations between individual metabolites and sensory attributes were elucidated. A high content of carnosine in the meat was associated with a low value of many sensory attributes related to meat flavor/taste. Surprsingly, IMP and inosine were in general not correlated with sensory attributes related...... to meat flavor/taste. Water-holding capacity and oxygen radical absorbance capacity (ORAC) of the meat were determined to elucidate the correlations between individual metabolites and these two parameters that are of importance for the technological meat quality. In conclusion, the present study reveals...

Migratory patterns and population structure among breeding and wintering red-breasted mergansers (Mergus serrator) and common mergansers (M. merganser)

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Pearce, J.M.; McCracken, K.G.; Christensen, Thomas K.; Zhuravlev, Y.N.

2009-01-01

Philopatry has long been assumed to structure populations of waterfowl and other species of birds genetically, especially via maternally transmitted mitochondrial DNA (mtDNA), yet other migratory behaviors and nesting ecology (use of ground vs. cavity sites) may also contribute to population genetic structure. We investigated the effects of migration and nesting ecology on the population genetic structure of two Holarctic waterfowl, the Red-breasted Merganser (Mergus serrator) and Common Merganser (M. merganser), using mtDNA control-region sequence data. Red-breasted Mergansers (a ground-nesting species) exhibited lower levels of population differentiation across their North American range, possibly as a result of post-Pleistocene range expansion and population growth. By contrast, Common Mergansers (a cavity-nesting species) breeding in western and eastern North America were strongly differentiated, as were continental groups in North America and Europe. Our hypothesis that population differentiation of breeding female Common Mergansers results from limited migration during non-breeding periods was not supported, in that equally heterogeneous mtDNA lineages were observed in males and females on several wintering areas. The interspecific differences in mtDNA patterns for these two closely related species may have resulted from factors related to nesting ecology (ground vs. cavity nesting) and responses to historical climate change.

PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes.

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Soto-Feliciano, Yadira M; Bartlebaugh, Jordan M E; Liu, Yunpeng; Sánchez-Rivera, Francisco J; Bhutkar, Arjun; Weintraub, Abraham S; Buenrostro, Jason D; Cheng, Christine S; Regev, Aviv; Jacks, Tyler E; Young, Richard A; Hemann, Michael T

2017-05-15

Developmental and lineage plasticity have been observed in numerous malignancies and have been correlated with tumor progression and drug resistance. However, little is known about the molecular mechanisms that enable such plasticity to occur. Here, we describe the function of the plant homeodomain finger protein 6 (PHF6) in leukemia and define its role in regulating chromatin accessibility to lineage-specific transcription factors. We show that loss of Phf6 in B-cell leukemia results in systematic changes in gene expression via alteration of the chromatin landscape at the transcriptional start sites of B-cell- and T-cell-specific factors. Additionally, Phf6 KO cells show significant down-regulation of genes involved in the development and function of normal B cells, show up-regulation of genes involved in T-cell signaling, and give rise to mixed-lineage lymphoma in vivo. Engagement of divergent transcriptional programs results in phenotypic plasticity that leads to altered disease presentation in vivo, tolerance of aberrant oncogenic signaling, and differential sensitivity to frontline and targeted therapies. These findings suggest that active maintenance of a precise chromatin landscape is essential for sustaining proper leukemia cell identity and that loss of a single factor (PHF6) can cause focal changes in chromatin accessibility and nucleosome positioning that render cells susceptible to lineage transition. © 2017 Soto-Feliciano et al.; Published by Cold Spring Harbor Laboratory Press.

Thymidine kinase 2 enzyme kinetics elucidate the mechanism of thymidine-induced mitochondrial DNA depletion.

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