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Sample records for evolving lineage-specific genes

  1. [Advances in lineage-specific genes].

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    Zhang, Huan-ping; Yin, Tong-ming

    2015-06-01

    Lineage-specific genes (LSGs) are defined as genes found in one particular taxonomic group but have no significant sequence similarity with genes from other lineages, which compose about 10%?20% of the total genes in the genome of a focal organism. LSGs were first uncovered in the yeast genome in 1996. The development of the whole genome sequencing leads to the emergence of studies on LSGs as a hot topic in comparative genomics. LSGs have been extensively studied on microbial species, lower marine organisms, plant (such as Arabidopsis thaliana, Oryza sativa, Populus), insects, primate, etc; the biological functions of LSGs are important to clarify the evolution and adaptability of a species. In this review, we summarize the progress of LSGs studies, including LSGs identification, gene characterization, origin and evolution of LSGs, biological function, and expression analysis of LSGs. In addition, we discuss the existing problems and future directions for studies in this area. Our purpose is to provide some unique insights into the researches of LSGs.

  2. Evolution of the globin gene family in deuterostomes: lineage-specific patterns of diversification and attrition.

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    Hoffmann, Federico G; Opazo, Juan C; Hoogewijs, David; Hankeln, Thomas; Ebner, Bettina; Vinogradov, Serge N; Bailly, Xavier; Storz, Jay F

    2012-07-01

    In the Metazoa, globin proteins display an underlying unity in tertiary structure that belies an extraordinary diversity in primary structures, biochemical properties, and physiological functions. Phylogenetic reconstructions can reveal which of these functions represent novel, lineage-specific innovations, and which represent ancestral functions that are shared with homologous globin proteins in other eukaryotes and even prokaryotes. To date, our understanding of globin diversity in deuterostomes has been hindered by a dearth of genomic sequence data from the Ambulacraria (echinoderms + hemichordates), the sister group of chordates, and the phylum Xenacoelomorpha, which includes xenoturbellids, acoelomorphs, and nemertodermatids. Here, we report the results of a phylogenetic and comparative genomic analysis of the globin gene repertoire of deuterostomes. We first characterized the globin genes of the acorn worm, Saccoglossus kowalevskii, a representative of the phylum Hemichordata. We then integrated genomic sequence data from the acorn worm into a comprehensive analysis of conserved synteny and phylogenetic relationships among globin genes from representatives of the eight lineages that comprise the superphylum Deuterostomia. The primary aims were 1) to unravel the evolutionary history of the globin gene superfamily in deuterostomes and 2) to use the estimated phylogeny to gain insights into the functional evolution of deuterostome globins. Results of our analyses indicate that the deuterostome common ancestor possessed a repertoire of at least four distinct globin paralogs and that different subsets of these ancestral genes have been retained in each of the descendant organismal lineages. In each major deuterostome group, a different subset of ancestral precursor genes underwent lineage-specific expansions of functional diversity through repeated rounds of gene duplication and divergence. By integrating results of the phylogenetic analysis with available

  3. Consistent and contrasting properties of lineage-specific genes in the apicomplexan parasites Plasmodium and Theileria

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    Kissinger Jessica C

    2008-04-01

    Full Text Available Abstract Background Lineage-specific genes, the genes that are restricted to a limited subset of related organisms, may be important in adaptation. In parasitic organisms, lineage-specific gene products are possible targets for vaccine development or therapeutics when these genes are absent from the host genome. Results In this study, we utilized comparative approaches based on a phylogenetic framework to characterize lineage-specific genes in the parasitic protozoan phylum Apicomplexa. Genes from species in two major apicomplexan genera, Plasmodium and Theileria, were categorized into six levels of lineage specificity based on a nine-species phylogeny. In both genera, lineage-specific genes tend to have a higher level of sequence divergence among sister species. In addition, species-specific genes possess a strong codon usage bias compared to other genes in the genome. We found that a large number of genus- or species-specific genes are putative surface antigens that may be involved in host-parasite interactions. Interestingly, the two parasite lineages exhibit several notable differences. In Plasmodium, the (G + C content at the third codon position increases with lineage specificity while Theileria shows the opposite trend. Surface antigens in Plasmodium are species-specific and mainly located in sub-telomeric regions. In contrast, surface antigens in Theileria are conserved at the genus level and distributed across the entire lengths of chromosomes. Conclusion Our results provide further support for the model that gene duplication followed by rapid divergence is a major mechanism for generating lineage-specific genes. The result that many lineage-specific genes are putative surface antigens supports the hypothesis that lineage-specific genes could be important in parasite adaptation. The contrasting properties between the lineage-specific genes in two major apicomplexan genera indicate that the mechanisms of generating lineage-specific genes

  4. Lineage-Specific Evolutionary Histories and Regulation of Major Starch Metabolism Genes during Banana Ripening

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    Jourda, Cyril; Cardi, Céline; Gibert, Olivier; Giraldo Toro, Andrès; Ricci, Julien; Mbéguié-A-Mbéguié, Didier; Yahiaoui, Nabila

    2016-01-01

    Starch is the most widespread and abundant storage carbohydrate in plants. It is also a major feature of cultivated bananas as it accumulates to large amounts during banana fruit development before almost complete conversion to soluble sugars during ripening. Little is known about the structure of major gene families involved in banana starch metabolism and their evolution compared to other species. To identify genes involved in banana starch metabolism and investigate their evolutionary history, we analyzed six gene families playing a crucial role in plant starch biosynthesis and degradation: the ADP-glucose pyrophosphorylases (AGPases), starch synthases (SS), starch branching enzymes (SBE), debranching enzymes (DBE), α-amylases (AMY) and β-amylases (BAM). Using comparative genomics and phylogenetic approaches, these genes were classified into families and sub-families and orthology relationships with functional genes in Eudicots and in grasses were identified. In addition to known ancestral duplications shaping starch metabolism gene families, independent evolution in banana and grasses also occurred through lineage-specific whole genome duplications for specific sub-families of AGPase, SS, SBE, and BAM genes; and through gene-scale duplications for AMY genes. In particular, banana lineage duplications yielded a set of AGPase, SBE and BAM genes that were highly or specifically expressed in banana fruits. Gene expression analysis highlighted a complex transcriptional reprogramming of starch metabolism genes during ripening of banana fruits. A differential regulation of expression between banana gene duplicates was identified for SBE and BAM genes, suggesting that part of starch metabolism regulation in the fruit evolved in the banana lineage. PMID:27994606

  5. Lineage-specific Evolutionary Histories and Regulation of Major Starch Metabolism Genes during Banana Ripening

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    Cyril Jourda

    2016-12-01

    Full Text Available Starch is the most widespread and abundant storage carbohydrate in plants. It is also a major feature of cultivated bananas as it accumulates to large amounts during banana fruit development before almost complete conversion to soluble sugars during ripening. Little is known about the structure of major gene families involved in banana starch metabolism and their evolution compared to other species. To identify genes involved in banana starch metabolism and investigate their evolutionary history, we analyzed six gene families playing a crucial role in plant starch biosynthesis and degradation: the ADP-glucose pyrophosphorylases (AGPases, starch synthases (SS, starch branching enzymes (SBE, debranching enzymes (DBE, -amylases (AMY and -amylases (BAM. Using comparative genomics and phylogenetic approaches, these genes were classified into families and sub-families and orthology relationships with functional genes in Eudicots and in grasses were identified. In addition to known ancestral duplications shaping starch metabolism gene families, independent evolution in banana and grasses also occurred through lineage-specific whole genome duplications for specific sub-families of AGPases, SS, SBE and BAM genes; and through gene-scale duplications for AMY genes. In particular, banana lineage duplications yielded a set of AGPases, SBE and BAM genes that were highly or specifically expressed in banana fruits. Gene expression analysis highlighted a complex transcriptional reprogramming of starch metabolism genes during ripening of banana fruits. A differential regulation of expression between banana gene duplicates was identified for SBE and BAM genes, suggesting that part of starch metabolism regulation in the fruit evolved in the banana lineage

  6. Lineage-Specific Evolutionary Histories and Regulation of Major Starch Metabolism Genes during Banana Ripening.

    Science.gov (United States)

    Jourda, Cyril; Cardi, Céline; Gibert, Olivier; Giraldo Toro, Andrès; Ricci, Julien; Mbéguié-A-Mbéguié, Didier; Yahiaoui, Nabila

    2016-01-01

    Starch is the most widespread and abundant storage carbohydrate in plants. It is also a major feature of cultivated bananas as it accumulates to large amounts during banana fruit development before almost complete conversion to soluble sugars during ripening. Little is known about the structure of major gene families involved in banana starch metabolism and their evolution compared to other species. To identify genes involved in banana starch metabolism and investigate their evolutionary history, we analyzed six gene families playing a crucial role in plant starch biosynthesis and degradation: the ADP-glucose pyrophosphorylases (AGPases), starch synthases (SS), starch branching enzymes (SBE), debranching enzymes (DBE), α-amylases (AMY) and β-amylases (BAM). Using comparative genomics and phylogenetic approaches, these genes were classified into families and sub-families and orthology relationships with functional genes in Eudicots and in grasses were identified. In addition to known ancestral duplications shaping starch metabolism gene families, independent evolution in banana and grasses also occurred through lineage-specific whole genome duplications for specific sub-families of AGPase, SS, SBE, and BAM genes; and through gene-scale duplications for AMY genes. In particular, banana lineage duplications yielded a set of AGPase, SBE and BAM genes that were highly or specifically expressed in banana fruits. Gene expression analysis highlighted a complex transcriptional reprogramming of starch metabolism genes during ripening of banana fruits. A differential regulation of expression between banana gene duplicates was identified for SBE and BAM genes, suggesting that part of starch metabolism regulation in the fruit evolved in the banana lineage.

  7. Papain-like cysteine proteases in Carica papaya: lineage-specific gene duplication and expansion.

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    Liu, Juan; Sharma, Anupma; Niewiara, Marie Jamille; Singh, Ratnesh; Ming, Ray; Yu, Qingyi

    2018-01-06

    Papain-like cysteine proteases (PLCPs), a large group of cysteine proteases structurally related to papain, play important roles in plant development, senescence, and defense responses. Papain, the first cysteine protease whose structure was determined by X-ray crystallography, plays a crucial role in protecting papaya from herbivorous insects. Except the four major PLCPs purified and characterized in papaya latex, the rest of the PLCPs in papaya genome are largely unknown. We identified 33 PLCP genes in papaya genome. Phylogenetic analysis clearly separated plant PLCP genes into nine subfamilies. PLCP genes are not equally distributed among the nine subfamilies and the number of PLCPs in each subfamily does not increase or decrease proportionally among the seven selected plant species. Papaya showed clear lineage-specific gene expansion in the subfamily III. Interestingly, all four major PLCPs purified from papaya latex, including papain, chymopapain, glycyl endopeptidase and caricain, were grouped into the lineage-specific expansion branch in the subfamily III. Mapping PLCP genes on chromosomes of five plant species revealed that lineage-specific expansions of PLCP genes were mostly derived from tandem duplications. We estimated divergence time of papaya PLCP genes of subfamily III. The major duplication events leading to lineage-specific expansion of papaya PLCP genes in subfamily III were estimated at 48 MYA, 34 MYA, and 16 MYA. The gene expression patterns of the papaya PLCP genes in different tissues were assessed by transcriptome sequencing and qRT-PCR. Most of the papaya PLCP genes of subfamily III expressed at high levels in leaf and green fruit tissues. Tandem duplications played the dominant role in affecting copy number of PLCPs in plants. Significant variations in size of the PLCP subfamilies among species may reflect genetic adaptation of plant species to different environments. The lineage-specific expansion of papaya PLCPs of subfamily III might

  8. In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer.

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    Pandi, Narayanan Sathiya; Suganya, Sivagurunathan; Rajendran, Suriliyandi

    2013-10-04

    Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. A Matter of Taste: Lineage-Specific Loss of Function of Taste Receptor Genes in Vertebrates

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    Marco Antinucci

    2017-11-01

    Full Text Available Vertebrates can perceive at least five different taste qualities, each of which is thought to have a specific role in the evolution of different species. The avoidance of potentially poisonous foods, which are generally bitter or sour tasting, and the search for more nutritious ones, those with high-fat and high-sugar content, are two of the most well-known examples. The study of taste genes encoding receptors that recognize ligands triggering taste sensations has helped to reconstruct several evolutionary adaptations to dietary changes. In addition, an increasing number of studies have focused on pseudogenes, genomic DNA sequences that have traditionally been considered defunct relatives of functional genes mostly because of the presence of deleterious mutations interrupting their open reading frames. The study of taste receptor pseudogenes has helped to shed light on how the evolutionary history of taste in vertebrates has been the result of a succession of gene gain and loss processes. This dynamic role in evolution has been explained by the “less-is-more” hypothesis, suggesting gene loss as a mechanism of evolutionary change in response to a dietary shift. This mini-review aims at depicting the major lineage-specific loss of function of taste receptor genes in vertebrates, stressing their evolutionary importance and recapitulating signatures of natural selection and their correlations with food habits.

  10. A Matter of Taste: Lineage-Specific Loss of Function of Taste Receptor Genes in Vertebrates

    Science.gov (United States)

    Antinucci, Marco; Risso, Davide

    2017-01-01

    Vertebrates can perceive at least five different taste qualities, each of which is thought to have a specific role in the evolution of different species. The avoidance of potentially poisonous foods, which are generally bitter or sour tasting, and the search for more nutritious ones, those with high-fat and high-sugar content, are two of the most well-known examples. The study of taste genes encoding receptors that recognize ligands triggering taste sensations has helped to reconstruct several evolutionary adaptations to dietary changes. In addition, an increasing number of studies have focused on pseudogenes, genomic DNA sequences that have traditionally been considered defunct relatives of functional genes mostly because of the presence of deleterious mutations interrupting their open reading frames. The study of taste receptor pseudogenes has helped to shed light on how the evolutionary history of taste in vertebrates has been the result of a succession of gene gain and loss processes. This dynamic role in evolution has been explained by the “less-is-more” hypothesis, suggesting gene loss as a mechanism of evolutionary change in response to a dietary shift. This mini-review aims at depicting the major lineage-specific loss of function of taste receptor genes in vertebrates, stressing their evolutionary importance and recapitulating signatures of natural selection and their correlations with food habits. PMID:29234667

  11. Variability among the most rapidly evolving plastid genomic regions is lineage-specific: implications of pairwise genome comparisons in Pyrus (Rosaceae and other angiosperms for marker choice.

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    Nadja Korotkova

    Full Text Available Plastid genomes exhibit different levels of variability in their sequences, depending on the respective kinds of genomic regions. Genes are usually more conserved while noncoding introns and spacers evolve at a faster pace. While a set of about thirty maximum variable noncoding genomic regions has been suggested to provide universally promising phylogenetic markers throughout angiosperms, applications often require several regions to be sequenced for many individuals. Our project aims to illuminate evolutionary relationships and species-limits in the genus Pyrus (Rosaceae-a typical case with very low genetic distances between taxa. In this study, we have sequenced the plastid genome of Pyrus spinosa and aligned it to the already available P. pyrifolia sequence. The overall p-distance of the two Pyrus genomes was 0.00145. The intergenic spacers between ndhC-trnV, trnR-atpA, ndhF-rpl32, psbM-trnD, and trnQ-rps16 were the most variable regions, also comprising the highest total numbers of substitutions, indels and inversions (potentially informative characters. Our comparative analysis of further plastid genome pairs with similar low p-distances from Oenothera (representing another rosid, Olea (asterids and Cymbidium (monocots showed in each case a different ranking of genomic regions in terms of variability and potentially informative characters. Only two intergenic spacers (ndhF-rpl32 and trnK-rps16 were consistently found among the 30 top-ranked regions. We have mapped the occurrence of substitutions and microstructural mutations in the four genome pairs. High AT content in specific sequence elements seems to foster frequent mutations. We conclude that the variability among the fastest evolving plastid genomic regions is lineage-specific and thus cannot be precisely predicted across angiosperms. The often lineage-specific occurrence of stem-loop elements in the sequences of introns and spacers also governs lineage-specific mutations. Sequencing

  12. 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, Phf6KO 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.

  13. Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses

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    Ryan Joseph F

    2011-01-01

    Full Text Available Abstract Background Mutations in the Otopetrin 1 gene (Otop1 in mice and fish produce an unusual bilateral vestibular pathology that involves the absence of otoconia without hearing impairment. The encoded protein, Otop1, is the only functionally characterized member of the Otopetrin Domain Protein (ODP family; the extended sequence and structural preservation of ODP proteins in metazoans suggest a conserved functional role. Here, we use the tools of sequence- and cytogenetic-based comparative genomics to study the Otop1 and the Otop2-Otop3 genes and to establish their genomic context in 25 vertebrates. We extend our evolutionary study to include the gene mutated in Usher syndrome (USH subtype 1G (Ush1g, both because of the head-to-tail clustering of Ush1g with Otop2 and because Otop1 and Ush1g mutations result in inner ear phenotypes. Results We established that OTOP1 is the boundary gene of an inversion polymorphism on human chromosome 4p16 that originated in the common human-chimpanzee lineage more than 6 million years ago. Other lineage-specific evolutionary events included a three-fold expansion of the Otop genes in Xenopus tropicalis and of Ush1g in teleostei fish. The tight physical linkage between Otop2 and Ush1g is conserved in all vertebrates. To further understand the functional organization of the Ushg1-Otop2 locus, we deduced a putative map of binding sites for CCCTC-binding factor (CTCF, a mammalian insulator transcription factor, from genome-wide chromatin immunoprecipitation-sequencing (ChIP-seq data in mouse and human embryonic stem (ES cells combined with detection of CTCF-binding motifs. Conclusions The results presented here clarify the evolutionary history of the vertebrate Otop and Ush1g families, and establish a framework for studying the possible interaction(s of Ush1g and Otop in developmental pathways.

  14. Lineage-specific evolution of bitter taste receptor genes in the giant and red pandas implies dietary adaptation.

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    Shan, Lei; Wu, Qi; Wang, Le; Zhang, Lei; Wei, Fuwen

    2017-11-23

    Bitter taste receptor genes (TAS2Rs) mediate bitterness perception in mammals. It is believed that these genes evolved in response to species-specific diets. The giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens styani) in the order Carnivora are specialized herbivores with an almost exclusive bamboo diet (>90% bamboo). Because bamboo is full of bitter tasting compounds, we hypothesized that adaptive evolution have occurred at TAS2R genes in giant and red pandas throughout the course of their dietary shift. Here, we characterized 195 TAS2Rs in nine Carnivora species and examined selective pressures on these genes. We found that both pandas harbour more putative functional TAS2Rs than other carnivores, and pseudogenized TAS2Rs in the giant panda are different from the red panda. The purifying selection on TAS2R1, TAS2R9 and TAS2R38 in the giant panda, and TAS2R62 in the red panda, has been strengthened throughout the course of adaptation to bamboo diet, while selective constraint on TAS2R4 and TAS2R38 in the red panda is relaxed. Remarkably, a few positively selected sites has been lineage-specifically detected on TAS2R42 in the giant panda. These results suggest an adaptive response in both pandas to a dietary shift from carnivory to herbivory, and TAS2Rs evolved independently in the two pandas. Our findings provide new insights into the molecular basis of mammalian sensory evolution and the process of adaptation to new ecological niches. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Negative spatial regulation of the lineage specific CyIIIa actin gene in the sea urchin embryo

    OpenAIRE

    Hough-Evans, Barbara R.; Franks, Roberta R.; Zeller, Robert W.; Roy J. Britten; Davidson, Eric H.

    1990-01-01

    The CyIIIa·CAT fusion gene was injected into Strongylocentrotus purpuratus eggs, together with excess ligated competitor sequences representing subregions of the CyIIIa regulatory domain. In this construct, the chloramphenicol acetyltransferase (CAT) reporter gene is placed under the control of the 2300 nucleotide upstream regulatory domain of the lineage-specific CyIIIa cytoskeletal actin gene. CAT mRNA was detected by in situ hybridization in serial sections of pluteus stage embryos derived...

  16. The Lineage-Specific Evolution of Aquaporin Gene Clusters Facilitated Tetrapod Terrestrial Adaptation

    OpenAIRE

    Finn, Roderick Nigel; Chauvigné, François; Hlidberg, Jón Baldur; Cutler, Christopher P.; Cerdà, Joan

    2014-01-01

    A major physiological barrier for aquatic organisms adapting to terrestrial life is dessication in the aerial environment. This barrier was nevertheless overcome by the Devonian ancestors of extant Tetrapoda, but the origin of specific molecular mechanisms that solved this water problem remains largely unknown. Here we show that an ancient aquaporin gene cluster evolved specifically in the sarcopterygian lineage, and subsequently diverged into paralogous forms of AQP2, -5, or -6 to mediate wa...

  17. Phylogenetics of Lophotrochozoan bHLH Genes and the Evolution of Lineage-Specific Gene Duplicates.

    Science.gov (United States)

    Bao, Yongbo; Xu, Fei; Shimeld, Sebastian M

    2017-04-01

    The gain and loss of genes encoding transcription factors is of importance to understanding the evolution of gene regulatory complexity. The basic helix-loop-helix (bHLH) genes encode a large superfamily of transcription factors. We systematically classify the bHLH genes from five mollusc, two annelid and one brachiopod genomes, tracing the pattern of bHLH gene evolution across these poorly studied Phyla. In total, 56-88 bHLH genes were identified in each genome, with most identifiable as members of previously described bilaterian families, or of new families we define. Of such families only one, Mesp, appears lost by all these species. Additional duplications have also played a role in the evolution of the bHLH gene repertoire, with many new lophotrochozoan-, mollusc-, bivalve-, or gastropod-specific genes defined. Using a combination of transcriptome mining, RT-PCR, and in situ hybridization we compared the expression of several of these novel genes in tissues and embryos of the molluscs Crassostrea gigas and Patella vulgata, finding both conserved expression and evidence for neofunctionalization. We also map the positions of the genes across these genomes, identifying numerous gene linkages. Some reflect recent paralog divergence by tandem duplication, others are remnants of ancient tandem duplications dating to the lophotrochozoan or bilaterian common ancestors. These data are built into a model of the evolution of bHLH genes in molluscs, showing formidable evolutionary stasis at the family level but considerable within-family diversification by tandem gene duplication. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  18. Use of pan-genome analysis for the identification of lineage-specific genes of Helicobacter pylori.

    Science.gov (United States)

    van Vliet, Arnoud H M

    2017-01-01

    The human bacterial pathogen Helicobacter pylori has a highly variable genome, with significant allelic and sequence diversity between isolates and even within well-characterised strains, hampering comparative genomics of H. pylori In this study, pan-genome analysis has been used to identify lineage-specific genes of H. pylori A total of 346 H. pylori genomes spanning the hpAfrica1, hpAfrica2, hpAsia2, hpEurope, hspAmerind and hspEAsia multilocus sequence typing (MLST) lineages were searched for genes specifically overrepresented or underrepresented in MLST lineages or associated with the cag pathogenicity island. The only genes overrepresented in cag-positive genomes were the cag pathogenicity island genes themselves. In contrast, a total of 125 genes were either overrepresented or underrepresented in one or more MLST lineages. Of these 125 genes, alcohol/aldehyde-reducing enzymes linked with acid resistance and production of toxic aldehydes were found to be overrepresented in African lineages. Conversely, the FecA2 ferric citrate receptor was missing from hspAmerind genomes, but present in all other lineages. This work shows the applicability of pan-genome analysis for identification of lineage-specific genes of H. pylori, facilitating further investigation to allow linkage of differential distribution of genes with disease outcome or virulence of H. pylori. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. The lineage-specific evolution of aquaporin gene clusters facilitated tetrapod terrestrial adaptation.

    Science.gov (United States)

    Finn, Roderick Nigel; Chauvigné, François; Hlidberg, Jón Baldur; Cutler, Christopher P; Cerdà, Joan

    2014-01-01

    A major physiological barrier for aquatic organisms adapting to terrestrial life is dessication in the aerial environment. This barrier was nevertheless overcome by the Devonian ancestors of extant Tetrapoda, but the origin of specific molecular mechanisms that solved this water problem remains largely unknown. Here we show that an ancient aquaporin gene cluster evolved specifically in the sarcopterygian lineage, and subsequently diverged into paralogous forms of AQP2, -5, or -6 to mediate water conservation in extant Tetrapoda. To determine the origin of these apomorphic genomic traits, we combined aquaporin sequencing from jawless and jawed vertebrates with broad taxon assembly of >2,000 transcripts amongst 131 deuterostome genomes and developed a model based upon Bayesian inference that traces their convergent roots to stem subfamilies in basal Metazoa and Prokaryota. This approach uncovered an unexpected diversity of aquaporins in every lineage investigated, and revealed that the vertebrate superfamily consists of 17 classes of aquaporins (Aqp0 - Aqp16). The oldest orthologs associated with water conservation in modern Tetrapoda are traced to a cluster of three aqp2-like genes in Actinistia that likely arose >500 Ma through duplication of an aqp0-like gene present in a jawless ancestor. In sea lamprey, we show that aqp0 first arose in a protocluster comprised of a novel aqp14 paralog and a fused aqp01 gene. To corroborate these findings, we conducted phylogenetic analyses of five syntenic nuclear receptor subfamilies, which, together with observations of extensive genome rearrangements, support the coincident loss of ancestral aqp2-like orthologs in Actinopterygii. We thus conclude that the divergence of sarcopterygian-specific aquaporin gene clusters was permissive for the evolution of water conservation mechanisms that facilitated tetrapod terrestrial adaptation.

  20. The lineage-specific evolution of aquaporin gene clusters facilitated tetrapod terrestrial adaptation.

    Directory of Open Access Journals (Sweden)

    Roderick Nigel Finn

    Full Text Available A major physiological barrier for aquatic organisms adapting to terrestrial life is dessication in the aerial environment. This barrier was nevertheless overcome by the Devonian ancestors of extant Tetrapoda, but the origin of specific molecular mechanisms that solved this water problem remains largely unknown. Here we show that an ancient aquaporin gene cluster evolved specifically in the sarcopterygian lineage, and subsequently diverged into paralogous forms of AQP2, -5, or -6 to mediate water conservation in extant Tetrapoda. To determine the origin of these apomorphic genomic traits, we combined aquaporin sequencing from jawless and jawed vertebrates with broad taxon assembly of >2,000 transcripts amongst 131 deuterostome genomes and developed a model based upon Bayesian inference that traces their convergent roots to stem subfamilies in basal Metazoa and Prokaryota. This approach uncovered an unexpected diversity of aquaporins in every lineage investigated, and revealed that the vertebrate superfamily consists of 17 classes of aquaporins (Aqp0 - Aqp16. The oldest orthologs associated with water conservation in modern Tetrapoda are traced to a cluster of three aqp2-like genes in Actinistia that likely arose >500 Ma through duplication of an aqp0-like gene present in a jawless ancestor. In sea lamprey, we show that aqp0 first arose in a protocluster comprised of a novel aqp14 paralog and a fused aqp01 gene. To corroborate these findings, we conducted phylogenetic analyses of five syntenic nuclear receptor subfamilies, which, together with observations of extensive genome rearrangements, support the coincident loss of ancestral aqp2-like orthologs in Actinopterygii. We thus conclude that the divergence of sarcopterygian-specific aquaporin gene clusters was permissive for the evolution of water conservation mechanisms that facilitated tetrapod terrestrial adaptation.

  1. Detecting lineage-specific adaptive evolution of brain-expressed genes in human using rhesus macaque as outgroup

    DEFF Research Database (Denmark)

    Yu, Xiao-Jing; Zheng, Hong-Kun; Wang, Jun

    2006-01-01

    Comparative genetic analysis between human and chimpanzee may detect genetic divergences responsible for human-specific characteristics. Previous studies have identified a series of genes that potentially underwent Darwinian positive selection during human evolution. However, without a closely...... related species as outgroup, it is difficult to identify human-lineage-specific changes, which is critical in delineating the biological uniqueness of humans. In this study, we conducted phylogeny-based analyses of 2633 human brain-expressed genes using rhesus macaque as the outgroup. We identified 47...... candidate genes showing strong evidence of positive selection in the human lineage. Genes with maximal expression in the brain showed a higher evolutionary rate in human than in chimpanzee. We observed that many immune-defense-related genes were under strong positive selection, and this trend was more...

  2. The polyphenol oxidase gene family in land plants: Lineage-specific duplication and expansion

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    Tran Lan T

    2012-08-01

    Full Text Available Abstract Background Plant polyphenol oxidases (PPOs are enzymes that typically use molecular oxygen to oxidize ortho-diphenols to ortho-quinones. These commonly cause browning reactions following tissue damage, and may be important in plant defense. Some PPOs function as hydroxylases or in cross-linking reactions, but in most plants their physiological roles are not known. To better understand the importance of PPOs in the plant kingdom, we surveyed PPO gene families in 25 sequenced genomes from chlorophytes, bryophytes, lycophytes, and flowering plants. The PPO genes were then analyzed in silico for gene structure, phylogenetic relationships, and targeting signals. Results Many previously uncharacterized PPO genes were uncovered. The moss, Physcomitrella patens, contained 13 PPO genes and Selaginella moellendorffii (spike moss and Glycine max (soybean each had 11 genes. Populus trichocarpa (poplar contained a highly diversified gene family with 11 PPO genes, but several flowering plants had only a single PPO gene. By contrast, no PPO-like sequences were identified in several chlorophyte (green algae genomes or Arabidopsis (A. lyrata and A. thaliana. We found that many PPOs contained one or two introns often near the 3’ terminus. Furthermore, N-terminal amino acid sequence analysis using ChloroP and TargetP 1.1 predicted that several putative PPOs are synthesized via the secretory pathway, a unique finding as most PPOs are predicted to be chloroplast proteins. Phylogenetic reconstruction of these sequences revealed that large PPO gene repertoires in some species are mostly a consequence of independent bursts of gene duplication, while the lineage leading to Arabidopsis must have lost all PPO genes. Conclusion Our survey identified PPOs in gene families of varying sizes in all land plants except in the genus Arabidopsis. While we found variation in intron numbers and positions, overall PPO gene structure is congruent with the phylogenetic

  3. Expansion of banana (Musa acuminata) gene families involved in ethylene biosynthesis and signalling after lineage-specific whole-genome duplications.

    Science.gov (United States)

    Jourda, Cyril; Cardi, Céline; Mbéguié-A-Mbéguié, Didier; Bocs, Stéphanie; Garsmeur, Olivier; D'Hont, Angélique; Yahiaoui, Nabila

    2014-05-01

    Whole-genome duplications (WGDs) are widespread in plants, and three lineage-specific WGDs occurred in the banana (Musa acuminata) genome. Here, we analysed the impact of WGDs on the evolution of banana gene families involved in ethylene biosynthesis and signalling, a key pathway for banana fruit ripening. Banana ethylene pathway genes were identified using comparative genomics approaches and their duplication modes and expression profiles were analysed. Seven out of 10 banana ethylene gene families evolved through WGD and four of them (1-aminocyclopropane-1-carboxylate synthase (ACS), ethylene-insensitive 3-like (EIL), ethylene-insensitive 3-binding F-box (EBF) and ethylene response factor (ERF)) were preferentially retained. Banana orthologues of AtEIN3 and AtEIL1, two major genes for ethylene signalling in Arabidopsis, were particularly expanded. This expansion was paralleled by that of EBF genes which are responsible for control of EIL protein levels. Gene expression profiles in banana fruits suggested functional redundancy for several MaEBF and MaEIL genes derived from WGD and subfunctionalization for some of them. We propose that EIL and EBF genes were co-retained after WGD in banana to maintain balanced control of EIL protein levels and thus avoid detrimental effects of constitutive ethylene signalling. In the course of evolution, subfunctionalization was favoured to promote finer control of ethylene signalling. © 2014 CIRAD New Phytologist © 2014 New Phytologist Trust.

  4. Helicobacter pylori evolution: lineage- specific adaptations in homologs of eukaryotic Sel1-like genes.

    Directory of Open Access Journals (Sweden)

    Masako Ogura

    2007-08-01

    Full Text Available Geographic partitioning is postulated to foster divergence of Helicobacter pylori populations as an adaptive response to local differences in predominant host physiology. H. pylori's ability to establish persistent infection despite host inflammatory responses likely involves active management of host defenses using bacterial proteins that may themselves be targets for adaptive evolution. Sequenced H. pylori genomes encode a family of eight or nine secreted proteins containing repeat motifs that are characteristic of the eukaryotic Sel1 regulatory protein, whereas the related Campylobacter and Wolinella genomes each contain only one or two such "Sel1-like repeat" (SLR genes ("slr genes". Signatures of positive selection (ratio of nonsynonymous to synonymous mutations, dN/dS = omega > 1 were evident in the evolutionary history of H. pylori slr gene family expansion. Sequence analysis of six of these slr genes (hp0160, hp0211, hp0235, hp0519, hp0628, and hp1117 from representative East Asian, European, and African H. pylori strains revealed that all but hp0628 had undergone positive selection, with different amino acids often selected in different regions. Most striking was a divergence of Japanese and Korean alleles of hp0519, with Japanese alleles having undergone particularly strong positive selection (omegaJ > 25, whereas alleles of other genes from these populations were intermingled. Homology-based structural modeling localized most residues under positive selection to SLR protein surfaces. Rapid evolution of certain slr genes in specific H. pylori lineages suggests a model of adaptive change driven by selection for fine-tuning of host responses, and facilitated by geographic isolation. Characterization of such local adaptations should help elucidate how H. pylori manages persistent infection, and potentially lead to interventions tailored to diverse human populations.

  5. SUMOylation of DRIL1 directs its transcriptional activity towards leukocyte lineage-specific genes.

    Directory of Open Access Journals (Sweden)

    Alexandre Prieur

    Full Text Available DRIL1 is an ARID family transcription factor that can immortalize primary mouse fibroblasts, bypass RAS(V12-induced cellular senescence and collaborate with RAS(V12 or MYC in mediating oncogenic transformation. It also activates immunoglobulin heavy chain transcription and engages in heterodimer formation with E2F to stimulate E2F-dependent transcription. Little, however, is known about the regulation of DRIL1 activity. Recently, DRIL1 was found to interact with the SUMO-conjugating enzyme Ubc9, but the functional relevance of this association has not been assessed. Here, we show that DRIL1 is sumoylated both in vitro and in vivo at lysine 398. Moreover, we provide evidence that PIASy functions as a specific SUMO E3-ligase for DRIL1 and promotes its sumoylation both in vitro and in vivo. Furthermore, consistent with the subnuclear localization of PIASy in the Matrix-Associated Region (MAR, SUMO-modified DRIL1 species are found exclusively in the MAR fraction. This post-translational modification interferes neither with the subcellular localization nor the DNA-binding activity of the protein. In contrast, DRIL1 sumoylation impairs its interaction with E2F1 in vitro and modifies its transcriptional activity in vivo, driving transcription of subset of genes regulating leukocyte fate. Taken together, these results identify sumoylation as a novel post-translational modification of DRIL1 that represents an important mechanism for targeting and modulating DRIL1 transcriptional activity.

  6. Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines

    Directory of Open Access Journals (Sweden)

    Nidal Ghosheh

    2016-01-01

    Full Text Available Human pluripotent stem cells- (hPSCs- derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4 which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models.

  7. Highly Synchronized Expression of Lineage-Specific Genes during In Vitro Hepatic Differentiation of Human Pluripotent Stem Cell Lines

    Science.gov (United States)

    Ghosheh, Nidal; Olsson, Björn; Edsbagge, Josefina; Küppers-Munther, Barbara; Van Giezen, Mariska; Asplund, Annika; Andersson, Tommy B.; Björquist, Petter; Carén, Helena; Simonsson, Stina; Sartipy, Peter; Synnergren, Jane

    2016-01-01

    Human pluripotent stem cells- (hPSCs-) derived hepatocytes have the potential to replace many hepatic models in drug discovery and provide a cell source for regenerative medicine applications. However, the generation of fully functional hPSC-derived hepatocytes is still a challenge. Towards gaining better understanding of the differentiation and maturation process, we employed a standardized protocol to differentiate six hPSC lines into hepatocytes and investigated the synchronicity of the hPSC lines by applying RT-qPCR to assess the expression of lineage-specific genes (OCT4, NANOG, T, SOX17, CXCR4, CER1, HHEX, TBX3, PROX1, HNF6, AFP, HNF4a, KRT18, ALB, AAT, and CYP3A4) which serve as markers for different stages during liver development. The data was evaluated using correlation and clustering analysis, demonstrating that the expression of these markers is highly synchronized and correlated well across all cell lines. The analysis also revealed a distribution of the markers in groups reflecting the developmental stages of hepatocytes. Functional analysis of the differentiated cells further confirmed their hepatic phenotype. Taken together, these results demonstrate, on the molecular level, the highly synchronized differentiation pattern across multiple hPSC lines. Moreover, this study provides additional understanding for future efforts to improve the functionality of hPSC-derived hepatocytes and thereby increase the value of related models. PMID:26949401

  8. Phylogenetic Analysis, Lineage-Specific Expansion and Functional Divergence of seed dormancy 4-Like Genes in Plants.

    Science.gov (United States)

    Subburaj, Saminathan; Cao, Shuanghe; Xia, Xianchun; He, Zhonghu

    2016-01-01

    The rice gene seed dormancy 4 (OsSdr4) functions in seed dormancy and is a major factor associated with pre-harvest sprouting (PHS). Although previous studies of this protein family were reported for rice and other species, knowledge of the evolution of genes homologous to OsSdr4 in plants remains inadequate. Fifty four Sdr4-like (hereafter designated Sdr4L) genes were identified in nine plant lineages including 36 species. Phylogenetic analysis placed these genes in eight subfamilies (I-VIII). Genes from the same lineage clustered together, supported by analysis of conserved motifs and exon-intron patterns. Segmental duplications were present in both dicot and monocot clusters, while tandemly duplicated genes occurred only in monocot clusters indicating that both tandem and segmental duplications contributed to expansion of the grass I and II subfamilies. Estimation of the approximate ages of the duplication events indicated that ancestral Sdr4 genes evolved from a common angiosperm ancestor, about 160 million years ago (MYA). Moreover, diversification of Sdr4L genes in mono and dicot plants was mainly associated with genome-wide duplication and speciation events. Functional divergence was observed in all subfamily pairs, except IV/VIIIa. Further analysis indicated that functional constraints between subfamily pairs I/II, I/VIIIb, II/VI, II/VIIIb, II/IV, and VI/VIIIb were statistically significant. Site and branch-site model analyses of positive selection suggested that these genes were under strong adaptive selection pressure. Critical amino acids detected for both functional divergence and positive selection were mostly located in the loops, pointing to functional importance of these regions in this protein family. In addition, differential expression studies by transcriptome atlas of 11 Sdr4L genes showed that the duplicated genes may have undergone divergence in expression between plant species. Our findings showed that Sdr4L genes are functionally divergent

  9. Characterization of MAT gene functions in the life cycle of Sclerotinia sclerotiorum reveals a lineage-specific MAT gene functioning in apothecium morphogenesis.

    Science.gov (United States)

    Doughan, Benjamin; Rollins, Jeffrey A

    2016-09-01

    Sclerotinia sclerotiorum (Lib.) de Bary is a phytopathogenic fungus that relies on the completion of the sexual cycle to initiate aerial infections. The sexual cycle produces apothecia required for inoculum dispersal. In this study, insight into the regulation of apothecial multicellular development was pursued through functional characterization of mating-type genes. These genes are hypothesized to encode master regulatory proteins required for aspects of sexual development ranging from fertilization through fertile fruiting body development. Experimentally, loss-of-function mutants were created for the conserved core mating-type genes (MAT1-1-1, and MAT1-2-1), and the lineage-specific genes found only in S. sclerotiorum and closely related fungi (MAT1-1-5, and MAT1-2-4). The MAT1-1-1, MAT1-1-5, and MAT1-2-1 mutants are able to form ascogonia but are blocked in all aspects of apothecium development. These mutants also exhibit defects in secondary sexual characters including lower numbers of spermatia. The MAT1-2-4 mutants are delayed in carpogenic germination accompanied with altered disc morphogenesis and ascospore production. They too produce lower numbers of spermatia. All four MAT gene mutants showed alterations in the expression of putative pheromone precursor (Ppg-1) and pheromone receptor (PreA, PreB) genes. Our findings support the involvement of MAT genes in sexual fertility, gene regulation, meiosis, and morphogenesis in S. sclerotiorum. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

  10. Profiling of gene duplication patterns of sequenced teleost genomes: evidence for rapid lineage-specific genome expansion mediated by recent tandem duplications.

    Science.gov (United States)

    Lu, Jianguo; Peatman, Eric; Tang, Haibao; Lewis, Joshua; Liu, Zhanjiang

    2012-06-15

    Gene duplication has had a major impact on genome evolution. Localized (or tandem) duplication resulting from unequal crossing over and whole genome duplication are believed to be the two dominant mechanisms contributing to vertebrate genome evolution. While much scrutiny has been directed toward discerning patterns indicative of whole-genome duplication events in teleost species, less attention has been paid to the continuous nature of gene duplications and their impact on the size, gene content, functional diversity, and overall architecture of teleost genomes. Here, using a Markov clustering algorithm directed approach we catalogue and analyze patterns of gene duplication in the four model teleost species with chromosomal coordinates: zebrafish, medaka, stickleback, and Tetraodon. Our analyses based on set size, duplication type, synonymous substitution rate (Ks), and gene ontology emphasize shared and lineage-specific patterns of genome evolution via gene duplication. Most strikingly, our analyses highlight the extraordinary duplication and retention rate of recent duplicates in zebrafish and their likely role in the structural and functional expansion of the zebrafish genome. We find that the zebrafish genome is remarkable in its large number of duplicated genes, small duplicate set size, biased Ks distribution toward minimal mutational divergence, and proportion of tandem and intra-chromosomal duplicates when compared with the other teleost model genomes. The observed gene duplication patterns have played significant roles in shaping the architecture of teleost genomes and appear to have contributed to the recent functional diversification and divergence of important physiological processes in zebrafish. We have analyzed gene duplication patterns and duplication types among the available teleost genomes and found that a large number of genes were tandemly and intrachromosomally duplicated, suggesting their origin of independent and continuous duplication

  11. Misregulation of spermatogenesis genes in Drosophila hybrids is lineage-specific and driven by the combined effects of sterility and fast male regulatory divergence.

    Science.gov (United States)

    Gomes, S; Civetta, A

    2014-09-01

    Hybrid male sterility is a common outcome of crosses between different species. Gene expression studies have found that a number of spermatogenesis genes are differentially expressed in sterile hybrid males, compared with parental species. Late-stage sperm development genes are particularly likely to be misexpressed, with fewer early-stage genes affected. Thus, a link has been posited between misexpression and sterility. A more recent alternative explanation for hybrid gene misexpression has been that it is independent of sterility and driven by divergent evolution of male-specific regulatory elements between species (faster male hypothesis). The faster male hypothesis predicts that misregulation of spermatogenesis genes should be independent of sterility and approximately the same in both hybrids, whereas sterility should only affect gene expression in sterile hybrids. To test the faster male hypothesis vs. the effect of sterility on gene misexpression, we analyse spermatogenesis gene expression in different species pairs of the Drosophila phylogeny, where hybrid male sterility occurs in only one direction of the interspecies cross (i.e. unidirectional sterility). We find significant differences among genes in misexpression with effects that are lineage-specific and caused by sterility or fast male regulatory divergence. © 2014 The Authors. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  12. Lineage-specific fragmentation and nuclear relocation of the mitochondrial cox2 gene in chlorophycean green algae (Chlorophyta).

    Science.gov (United States)

    Rodríguez-Salinas, Elizabeth; Riveros-Rosas, Héctor; Li, Zhongkui; Fucíková, Karolina; Brand, Jerry J; Lewis, Louise A; González-Halphen, Diego

    2012-07-01

    In most eukaryotes the subunit 2 of cytochrome c oxidase (COX2) is encoded in intact mitochondrial genes. Some green algae, however, exhibit split cox2 genes (cox2a and cox2b) encoding two polypeptides (COX2A and COX2B) that form a heterodimeric COX2 subunit. Here, we analyzed the distribution of intact and split cox2 gene sequences in 39 phylogenetically diverse green algae in phylum Chlorophyta obtained from databases (28 sequences from 22 taxa) and from new cox2 data generated in this work (23 sequences from 18 taxa). Our results support previous observations based on a smaller number of taxa, indicating that algae in classes Prasinophyceae, Ulvophyceae, and Trebouxiophyceae contain orthodox, intact mitochondrial cox2 genes. In contrast, all of the algae in Chlorophyceae that we examined exhibited split cox2 genes, and could be separated into two groups: one that has a mitochondrion-localized cox2a gene and a nucleus-localized cox2b gene ("Scenedesmus-like"), and another that has both cox2a and cox2b genes in the nucleus ("Chlamydomonas-like"). The location of the split cox2a and cox2b genes was inferred using five different criteria: differences in amino acid sequences, codon usage (mitochondrial vs. nuclear), codon preference (third position frequencies), presence of nucleotide sequences encoding mitochondrial targeting sequences and presence of spliceosomal introns. Distinct green algae could be grouped according to the form of cox2 gene they contain: intact or fragmented, mitochondrion- or nucleus-localized, and intron-containing or intron-less. We present a model describing the events that led to mitochondrial cox2 gene fragmentation and the independent and sequential migration of cox2a and cox2b genes to the nucleus in chlorophycean green algae. We also suggest that the distribution of the different forms of the cox2 gene provides important insights into the phylogenetic relationships among major groups of Chlorophyceae.

  13. Multi-species sequence comparison reveals dynamic evolution of the elastin gene that has involved purifying selection and lineage-specific insertions/deletions

    Directory of Open Access Journals (Sweden)

    Green Eric D

    2004-05-01

    Full Text Available Abstract Background The elastin gene (ELN is implicated as a factor in both supravalvular aortic stenosis (SVAS and Williams Beuren Syndrome (WBS, two diseases involving pronounced complications in mental or physical development. Although the complete spectrum of functional roles of the processed gene product remains to be established, these roles are inferred to be analogous in human and mouse. This view is supported by genomic sequence comparison, in which there are no large-scale differences in the ~1.8 Mb sequence block encompassing the common region deleted in WBS, with the exception of an overall reversed physical orientation between human and mouse. Results Conserved synteny around ELN does not translate to a high level of conservation in the gene itself. In fact, ELN orthologs in mammals show more sequence divergence than expected for a gene with a critical role in development. The pattern of divergence is non-conventional due to an unusually high ratio of gaps to substitutions. Specifically, multi-sequence alignments of eight mammalian sequences reveal numerous non-aligning regions caused by species-specific insertions and deletions, in spite of the fact that the vast majority of aligning sites appear to be conserved and undergoing purifying selection. Conclusions The pattern of lineage-specific, in-frame insertions/deletions in the coding exons of ELN orthologous genes is unusual and has led to unique features of the gene in each lineage. These differences may indicate that the gene has a slightly different functional mechanism in mammalian lineages, or that the corresponding regions are functionally inert. Identified regions that undergo purifying selection reflect a functional importance associated with evolutionary pressure to retain those features.

  14. Evolutionary genomics reveals lineage-specific gene loss and rapid evolution of a sperm-specific ion channel complex: CatSpers and CatSperbeta.

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    Xinjiang Cai

    Full Text Available The mammalian CatSper ion channel family consists of four sperm-specific voltage-gated Ca2+ channels that are crucial for sperm hyperactivation and male fertility. All four CatSper subunits are believed to assemble into a heteromultimeric channel complex, together with an auxiliary subunit, CatSperbeta. Here, we report a comprehensive comparative genomics study and evolutionary analysis of CatSpers and CatSperbeta, with important correlation to physiological significance of molecular evolution of the CatSper channel complex. The development of the CatSper channel complex with four CatSpers and CatSperbeta originated as early as primitive metazoans such as the Cnidarian Nematostella vectensis. Comparative genomics revealed extensive lineage-specific gene loss of all four CatSpers and CatSperbeta through metazoan evolution, especially in vertebrates. The CatSper channel complex underwent rapid evolution and functional divergence, while distinct evolutionary constraints appear to have acted on different domains and specific sites of the four CatSper genes. These results reveal unique evolutionary characteristics of sperm-specific Ca2+ channels and their adaptation to sperm biology through metazoan evolution.

  15. How Genes Evolve

    Indian Academy of Sciences (India)

    evolutionary history of duplicated genes within a given lineage. The timings of gene duplication events can be inferred ... evolutionary history of the creatures in which various globin genes are found, the timings of the ..... But I cannot find heart to give any part of my life for money-making purposes ... : In 1901, one of the large ...

  16. Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish

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    Mogensen Knud

    2003-07-01

    Full Text Available Abstract Background The high degree of sequence conservation between coding regions in fish and mammals can be exploited to identify genes in mammalian genomes by comparison with the sequence of similar genes in fish. Conversely, experimentally characterized mammalian genes may be used to annotate fish genomes. However, gene families that escape this principle include the rapidly diverging cytokines that regulate the immune system, and their receptors. A classic example is the class II helical cytokines (HCII including type I, type II and lambda interferons, IL10 related cytokines (IL10, IL19, IL20, IL22, IL24 and IL26 and their receptors (HCRII. Despite the report of a near complete pufferfish (Takifugu rubripes genome sequence, these genes remain undescribed in fish. Results We have used an original strategy based both on conserved amino acid sequence and gene structure to identify HCII and HCRII in the genome of another pufferfish, Tetraodon nigroviridis that is amenable to laboratory experiments. The 15 genes that were identified are highly divergent and include a single interferon molecule, three IL10 related cytokines and their potential receptors together with two Tissue Factor (TF. Some of these genes form tandem clusters on the Tetraodon genome. Their expression pattern was determined in different tissues. Most importantly, Tetraodon interferon was identified and we show that the recombinant protein can induce antiviral MX gene expression in Tetraodon primary kidney cells. Similar results were obtained in Zebrafish which has 7 MX genes. Conclusion We propose a scheme for the evolution of HCII and their receptors during the radiation of bony vertebrates and suggest that the diversification that played an important role in the fine-tuning of the ancestral mechanism for host defense against infections probably followed different pathways in amniotes and fish.

  17. Sequencing analysis of 20,000 full-length cDNA clones from cassava reveals lineage specific expansions in gene families related to stress response

    Directory of Open Access Journals (Sweden)

    Sakaki Yoshiyuki

    2007-12-01

    Full Text Available Abstract Background Cassava, an allotetraploid known for its remarkable tolerance to abiotic stresses is an important source of energy for humans and animals and a raw material for many industrial processes. A full-length cDNA library of cassava plants under normal, heat, drought, aluminum and post harvest physiological deterioration conditions was built; 19968 clones were sequence-characterized using expressed sequence tags (ESTs. Results The ESTs were assembled into 6355 contigs and 9026 singletons that were further grouped into 10577 scaffolds; we found 4621 new cassava sequences and 1521 sequences with no significant similarity to plant protein databases. Transcripts of 7796 distinct genes were captured and we were able to assign a functional classification to 78% of them while finding more than half of the enzymes annotated in metabolic pathways in Arabidopsis. The annotation of sequences that were not paired to transcripts of other species included many stress-related functional categories showing that our library is enriched with stress-induced genes. Finally, we detected 230 putative gene duplications that include key enzymes in reactive oxygen species signaling pathways and could play a role in cassava stress response features. Conclusion The cassava full-length cDNA library here presented contains transcripts of genes involved in stress response as well as genes important for different areas of cassava research. This library will be an important resource for gene discovery, characterization and cloning; in the near future it will aid the annotation of the cassava genome.

  18. Evolution of evolvability in gene regulatory networks.

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    Anton Crombach

    Full Text Available Gene regulatory networks are perhaps the most important organizational level in the cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of genes. For the last decade, the study of such networks has been fueled by large-scale experiments and renewed attention from the theoretical field. Different models have been proposed to, for instance, investigate expression dynamics, explain the network topology we observe in bacteria and yeast, and for the analysis of evolvability and robustness of such networks. Yet how these gene regulatory networks evolve and become evolvable remains an open question. An individual-oriented evolutionary model is used to shed light on this matter. Each individual has a genome from which its gene regulatory network is derived. Mutations, such as gene duplications and deletions, alter the genome, while the resulting network determines the gene expression pattern and hence fitness. With this protocol we let a population of individuals evolve under Darwinian selection in an environment that changes through time. Our work demonstrates that long-term evolution of complex gene regulatory networks in a changing environment can lead to a striking increase in the efficiency of generating beneficial mutations. We show that the population evolves towards genotype-phenotype mappings that allow for an orchestrated network-wide change in the gene expression pattern, requiring only a few specific gene indels. The genes involved are hubs of the networks, or directly influencing the hubs. Moreover, throughout the evolutionary trajectory the networks maintain their mutational robustness. In other words, evolution in an alternating environment leads to a network that is sensitive to a small class of beneficial mutations, while the majority of mutations remain neutral: an example of evolution of evolvability.

  19. Lineage-specific evolution of Methylthioalkylmalate synthases (MAMs involved in glucosinolates biosynthesis

    Directory of Open Access Journals (Sweden)

    Jifang eZhang

    2015-02-01

    Full Text Available Methylthioalkylmalate synthases (MAMs encoded by MAM genes are central to the diversification of the glucosinolates, which are important secondary metabolites in Brassicaceae species. However, the evolutionary pathway of MAM genes is poorly understood. We analyzed the phylogenetic and synteny relationships of MAM genes from 13 sequenced Brassicaceae species. Based on these analyses, we propose that the syntenic loci of MAM genes, which underwent frequent tandem duplications, divided into two independent lineage-specific evolution routes and were driven by positive selection after the divergence from Aethionema arabicum. In the lineage I species Capsella rubella, Camelina sativa, Arabidopsis lyrata, and A. thaliana, the MAM loci evolved three tandem genes encoding enzymes responsible for the biosynthesis of aliphatic glucosinolates with different carbon chain-lengths. In lineage II species, the MAM loci encode enzymes responsible for the biosynthesis of short-chain aliphatic glucosinolates. Our proposed model of the evolutionary pathway of MAM genes will be useful for understanding the specific function of these genes in Brassicaceae species.

  20. Lineage-specific evolution of Methylthioalkylmalate synthases (MAMs) involved in glucosinolates biosynthesis.

    Science.gov (United States)

    Zhang, Jifang; Wang, Xiaobo; Cheng, Feng; Wu, Jian; Liang, Jianli; Yang, Wencai; Wang, Xiaowu

    2015-01-01

    Methylthioalkylmalate synthases (MAMs) encoded by MAM genes are central to the diversification of the glucosinolates, which are important secondary metabolites in Brassicaceae species. However, the evolutionary pathway of MAM genes is poorly understood. We analyzed the phylogenetic and synteny relationships of MAM genes from 13 sequenced Brassicaceae species. Based on these analyses, we propose that the syntenic loci of MAM genes, which underwent frequent tandem duplications, divided into two independent lineage-specific evolution routes and were driven by positive selection after the divergence from Aethionema arabicum. In the lineage I species Capsella rubella, Camelina sativa, Arabidopsis lyrata, and A. thaliana, the MAM loci evolved three tandem genes encoding enzymes responsible for the biosynthesis of aliphatic glucosinolates with different carbon chain-lengths. In lineage II species, the MAM loci encode enzymes responsible for the biosynthesis of short-chain aliphatic glucosinolates. Our proposed model of the evolutionary pathway of MAM genes will be useful for understanding the specific function of these genes in Brassicaceae species.

  1. Evolving chromosomes and gene regulatory networks

    Indian Academy of Sciences (India)

    Aswin

    Many processes change genomes. Koonin and Wolf. 2008. Page 5 .. including horizontal gene transfer. Koonin and Wolf. 2008. Page 6. Horizontal gene transfer. Drastic modification of genetic material. Rapid exploration of ne niches and phenot pes. Page 7. Horizontal gene transfer regulates. New selective forces for gene ...

  2. Duplicated genes evolve independently in allopolyploid cotton.

    Science.gov (United States)

    Richard C. Cronn; Randall L. Small; Jonathan F. Wendel

    1999-01-01

    Of the many processes that generate gene duplications, polyploidy is unique in that entire genomes are duplicated. This process has been important in the evolution of many eukaryotic groups, and it occurs with high frequency in plants. Recent evidence suggests that polyploidization may be accompanied by rapid genomic changes, but the evolutionary fate of discrete loci...

  3. The Evolving Definition of the Term "Gene".

    Science.gov (United States)

    Portin, Petter; Wilkins, Adam

    2017-04-01

    This paper presents a history of the changing meanings of the term "gene," over more than a century, and a discussion of why this word, so crucial to genetics, needs redefinition today. In this account, the first two phases of 20th century genetics are designated the "classical" and the "neoclassical" periods, and the current molecular-genetic era the "modern period." While the first two stages generated increasing clarity about the nature of the gene, the present period features complexity and confusion. Initially, the term "gene" was coined to denote an abstract "unit of inheritance," to which no specific material attributes were assigned. As the classical and neoclassical periods unfolded, the term became more concrete, first as a dimensionless point on a chromosome, then as a linear segment within a chromosome, and finally as a linear segment in the DNA molecule that encodes a polypeptide chain. This last definition, from the early 1960s, remains the one employed today, but developments since the 1970s have undermined its generality. Indeed, they raise questions about both the utility of the concept of a basic "unit of inheritance" and the long implicit belief that genes are autonomous agents. Here, we review findings that have made the classic molecular definition obsolete and propose a new one based on contemporary knowledge. Copyright © 2017 by the Genetics Society of America.

  4. Proteome analysis of early lineage specification in bovine embryos.

    Science.gov (United States)

    Demant, Myriam; Deutsch, Daniela R; Fröhlich, Thomas; Wolf, Eckhard; Arnold, Georg J

    2015-02-01

    During mammalian embryo development, the zygote undergoes embryonic cleavage in the oviduct and reaches the uterus at the morula stage, when compaction and early lineage specification take place. To increase knowledge about the associated changes of the embryonic protein repertoire, we performed a comprehensive proteomic analysis of in vitro produced bovine morulae and blastocysts (six biological replicates), using an iTRAQ-based approach. A total of 560 proteins were identified of which 502 were quantified. The abundance of 140 proteins was significantly different between morulae and blastocysts, among them nucleophosmin (NPM1), eukaryotic translation initiation factor 5A-1 (EIF5A), receptor of activated protein kinase C 1 (GNB2L1/RACK1), and annexin A6 (ANXA6) with increased, and glutathione S-transferase mu 3 (GSTM3), peroxiredoxin 2 (PRDX2), and aldo-keto reductase family 1 member B1 (AKR1B1) with decreased abundance in blastocysts. Seventy-three percent of abundance altered proteins increased, reflecting an increase of translation activity in this period. This is further supported by an increase in the abundance of proteins involved in the translation machinery and the synthesis of ATP. Additionally, a complementary 2D saturation DIGE analysis led to the detection of protein isoforms, e.g. of GSTM3 and PRDX2, relevant for this period of mammalian development, and exemplarily verified the results of the iTRAQ approach. In summary, our systematic differential proteome analysis of bovine morulae and blastocysts revealed new molecular correlates of early lineage specification and differentiation events during bovine embryogenesis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Lineage-Specific Restraint of Pituitary Gonadotroph Cell Adenoma Growth

    Science.gov (United States)

    Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Ben-Shlomo, Anat; Wawrowsky, Kolja; Toledano, Yoel; Tong, Yunguang; Kovacs, Kalman; Scheithauer, Bernd; Melmed, Shlomo

    2011-01-01

    Although pituitary adenomas are usually benign, unique trophic mechanisms restraining cell proliferation are unclear. As GH-secreting adenomas are associated with p53/p21-dependent senescence, we tested mechanisms constraining non-functioning pituitary adenoma growth. Thirty six gonadotroph-derived non-functioning pituitary adenomas all exhibited DNA damage, but undetectable p21 expression. However, these adenomas all expressed p16, and >90% abundantly expressed cytoplasmic clusterin associated with induction of the Cdk inhibitor p15 in 70% of gonadotroph and in 26% of somatotroph lineage adenomas (p = 0.006). Murine LβT2 and αT3 gonadotroph pituitary cells, and αGSU.PTTG transgenic mice with targeted gonadotroph cell adenomas also abundantly expressed clusterin and exhibited features of oncogene-induced senescence as evidenced by C/EBPβ and C/EBPδ induction. In turn, C/EBPs activated the clusterin promoter ∼5 fold, and elevated clusterin subsequently elicited p15 and p16 expression, acting to arrest murine gonadotroph cell proliferation. In contrast, specific clusterin suppression by RNAis enhanced gonadotroph proliferation. FOXL2, a tissue-specific gonadotroph lineage factor, also induced the clusterin promoter ∼3 fold in αT3 pituitary cells. As nine of 12 pituitary carcinomas were devoid of clusterin expression, this protein may limit proliferation of benign adenomatous pituitary cells. These results point to lineage-specific pathways restricting uncontrolled murine and human pituitary gonadotroph adenoma cell growth. PMID:21464964

  6. Structure of Nascent Chromatin Is Essential for Hematopoietic Lineage Specification.

    Science.gov (United States)

    Petruk, Svetlana; Mariani, Samanta A; De Dominici, Marco; Porazzi, Patrizia; Minieri, Valentina; Cai, Jingli; Iacovitti, Lorraine; Flomenberg, Neal; Calabretta, Bruno; Mazo, Alexander

    2017-04-11

    The role of chromatin structure in lineage commitment of multipotent hematopoietic progenitors (HPCs) is presently unclear. We show here that CD34 + HPCs possess a post-replicative chromatin globally devoid of the repressive histone mark H3K27me3. This H3K27-unmodified chromatin is required for recruitment of lineage-determining transcription factors (TFs) C/EBPα, PU.1, and GATA-1 to DNA just after DNA replication upon cytokine-induced myeloid or erythroid commitment. Blocking DNA replication or increasing H3K27me3 levels prevents recruitment of these TFs to DNA and suppresses cytokine-induced erythroid or myeloid differentiation. However, H3K27me3 is rapidly associated with nascent DNA in more primitive human and murine HPCs. Treatment of these cells with instructive cytokines leads to a significant delay in accumulation of H3K27me3 in nascent chromatin due to activity of the H3K27me3 demethylase UTX. Thus, HPCs utilize special mechanisms of chromatin modification for recruitment of specific TFs to DNA during early stages of lineage specification. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Structure of Nascent Chromatin Is Essential for Hematopoietic Lineage Specification

    Directory of Open Access Journals (Sweden)

    Svetlana Petruk

    2017-04-01

    Full Text Available The role of chromatin structure in lineage commitment of multipotent hematopoietic progenitors (HPCs is presently unclear. We show here that CD34+ HPCs possess a post-replicative chromatin globally devoid of the repressive histone mark H3K27me3. This H3K27-unmodified chromatin is required for recruitment of lineage-determining transcription factors (TFs C/EBPα, PU.1, and GATA-1 to DNA just after DNA replication upon cytokine-induced myeloid or erythroid commitment. Blocking DNA replication or increasing H3K27me3 levels prevents recruitment of these TFs to DNA and suppresses cytokine-induced erythroid or myeloid differentiation. However, H3K27me3 is rapidly associated with nascent DNA in more primitive human and murine HPCs. Treatment of these cells with instructive cytokines leads to a significant delay in accumulation of H3K27me3 in nascent chromatin due to activity of the H3K27me3 demethylase UTX. Thus, HPCs utilize special mechanisms of chromatin modification for recruitment of specific TFs to DNA during early stages of lineage specification.

  8. Core genome components and lineage specific expansions in malaria parasites Plasmodium

    Directory of Open Access Journals (Sweden)

    Gu Jianying

    2010-12-01

    Full Text Available Abstract Background The increasing resistance of Plasmodium, the malaria parasites, to multiple commonly used drugs has underscored the urgent need to develop effective antimalarial drugs and vaccines. The new direction of genomics-driven target discovery has become possible with the completion of parasite genome sequencing, which can lead us to a better understanding of how the parasites develop the genetic variability that is associated with their response to environmental challenges and other adaptive phenotypes. Results We present the results of a comprehensive analysis of the genomes of six Plasmodium species, including two species that infect humans, one that infects monkeys, and three that infect rodents. The core genome shared by all six species is composed of 3,351 genes, which make up about 22%-65% of the genome repertoire. These components play important roles in fundamental functions as well as in parasite-specific activities. We further investigated the distribution and features of genes that have been expanded in specific Plasmodium lineage(s. Abundant duplicate genes are present in the six species, with 5%-9% of the whole genomes composed lineage specific radiations. The majority of these gene families are hypothetical proteins with unknown functions; a few may have predicted roles such as antigenic variation. Conclusions The core genome components in the malaria parasites have functions ranging from fundamental biological processes to roles in the complex networks that sustain the parasite-specific lifestyles appropriate to different hosts. They represent the minimum requirement to maintain a successful life cycle that spans vertebrate hosts and mosquito vectors. Lineage specific expansions (LSEs have given rise to abundant gene families in Plasmodium. Although the functions of most families remain unknown, these LSEs could reveal components in parasite networks that, by their enhanced genetic variability, can contribute to

  9. EVOLVE

    CERN Document Server

    Deutz, André; Schütze, Oliver; Legrand, Pierrick; Tantar, Emilia; Tantar, Alexandru-Adrian

    2017-01-01

    This book comprises nine selected works on numerical and computational methods for solving multiobjective optimization, game theory, and machine learning problems. It provides extended versions of selected papers from various fields of science such as computer science, mathematics and engineering that were presented at EVOLVE 2013 held in July 2013 at Leiden University in the Netherlands. The internationally peer-reviewed papers include original work on important topics in both theory and applications, such as the role of diversity in optimization, statistical approaches to combinatorial optimization, computational game theory, and cell mapping techniques for numerical landscape exploration. Applications focus on aspects including robustness, handling multiple objectives, and complex search spaces in engineering design and computational biology.

  10. Aging-like Phenotype and Defective Lineage Specification in SIRT1-Deleted Hematopoietic Stem and Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Pauline Rimmelé

    2014-07-01

    Full Text Available Aging hematopoietic stem cells (HSCs exhibit defective lineage specification that is thought to be central to increased incidence of myeloid malignancies and compromised immune competence in the elderly. Mechanisms underlying these age-related defects remain largely unknown. We show that the deacetylase Sirtuin (SIRT1 is required for homeostatic HSC maintenance. Differentiation of young SIRT1-deleted HSCs is skewed toward myeloid lineage associated with a significant decline in the lymphoid compartment, anemia, and altered expression of associated genes. Combined with HSC accumulation of damaged DNA and expression patterns of age-linked molecules, these have striking overlaps with aged HSCs. We further show that SIRT1 controls HSC homeostasis via the longevity transcription factor FOXO3. These findings suggest that SIRT1 is essential for HSC homeostasis and lineage specification. They also indicate that SIRT1 might contribute to delaying HSC aging.

  11. Gap Gene Regulatory Dynamics Evolve along a Genotype Network

    Science.gov (United States)

    Crombach, Anton; Wotton, Karl R.; Jiménez-Guri, Eva; Jaeger, Johannes

    2016-01-01

    Developmental gene networks implement the dynamic regulatory mechanisms that pattern and shape the organism. Over evolutionary time, the wiring of these networks changes, yet the patterning outcome is often preserved, a phenomenon known as “system drift.” System drift is illustrated by the gap gene network—involved in segmental patterning—in dipteran insects. In the classic model organism Drosophila melanogaster and the nonmodel scuttle fly Megaselia abdita, early activation and placement of gap gene expression domains show significant quantitative differences, yet the final patterning output of the system is essentially identical in both species. In this detailed modeling analysis of system drift, we use gene circuits which are fit to quantitative gap gene expression data in M. abdita and compare them with an equivalent set of models from D. melanogaster. The results of this comparative analysis show precisely how compensatory regulatory mechanisms achieve equivalent final patterns in both species. We discuss the larger implications of the work in terms of “genotype networks” and the ways in which the structure of regulatory networks can influence patterns of evolutionary change (evolvability). PMID:26796549

  12. Nonlinear Dynamics in Gene Regulation Promote Robustness and Evolvability of Gene Expression Levels.

    Directory of Open Access Journals (Sweden)

    Arno Steinacher

    Full Text Available Cellular phenotypes underpinned by regulatory networks need to respond to evolutionary pressures to allow adaptation, but at the same time be robust to perturbations. This creates a conflict in which mutations affecting regulatory networks must both generate variance but also be tolerated at the phenotype level. Here, we perform mathematical analyses and simulations of regulatory networks to better understand the potential trade-off between robustness and evolvability. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics, through the creation of regions presenting sudden changes in phenotype with small changes in genotype. For genotypes embedding low levels of nonlinearity, robustness and evolvability correlate negatively and almost perfectly. By contrast, genotypes embedding nonlinear dynamics allow expression levels to be robust to small perturbations, while generating high diversity (evolvability under larger perturbations. Thus, nonlinearity breaks the robustness-evolvability trade-off in gene expression levels by allowing disparate responses to different mutations. Using analytical derivations of robustness and system sensitivity, we show that these findings extend to a large class of gene regulatory network architectures and also hold for experimentally observed parameter regimes. Further, the effect of nonlinearity on the robustness-evolvability trade-off is ensured as long as key parameters of the system display specific relations irrespective of their absolute values. We find that within this parameter regime genotypes display low and noisy expression levels. Examining the phenotypic effects of mutations, we find an inverse correlation between robustness and evolvability that breaks only with nonlinearity in the network dynamics. Our results provide a possible solution to the robustness-evolvability trade-off, suggest

  13. Lineage specific recombination rates and microevolution in Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    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

  14. A critical role for TCF-1 in T-lineage specification and differentiation

    Science.gov (United States)

    Weber, Brittany Nicole; Chi, Anthony Wei-Shine; Chavez, Alejandro; Yashiro-Ohtani, Yumi; Yang, Qi; Shestova, Olga; Bhandoola, Avinash

    2011-01-01

    The vertebrate thymus provides an inductive environment for T-cell development. Within the thymus, Notch signals are indispensable for imposing the T-cell fate on multipotential hematopoietic progenitors, but the downstream effectors that impart T-lineage specification and commitment are not well understood. Here we show that transcription factor, T-cell factor 1 (TCF-1), is a critical regulator in T-cell specification. TCF-1 is highly expressed in the earliest thymic progenitors, and its expression is upregulated by Notch signals. Most importantly, when TCF-1 is forcibly expressed in BM progenitors, it drives the development of T-lineage cells in the absence of T-inductive Notch1 signals. Further characterization of these TCF-1-induced cells revealed expression of many T-lineage genes, including T-cell specific transcription factors Gata3, Bcl11b, and components of the T-cell receptor. Our data suggest a model where Notch signals induce TCF-1, and TCF-1 in turn imprints the T-cell fate by upregulating expression of T-cell essential genes. PMID:21814277

  15. Exchange of core chromosomes and horizontal transfer of lineage-specific chromosomes in Fusarium oxysporum.

    Science.gov (United States)

    Vlaardingerbroek, Ido; Beerens, Bas; Rose, Laura; Fokkens, Like; Cornelissen, Ben J C; Rep, Martijn

    2016-11-01

    Horizontal transfer of supernumerary or lineage-specific (LS) chromosomes has been described in a number of plant pathogenic filamentous fungi. So far it was not known whether transfer is restricted to chromosomes of certain size or properties, or whether 'core' chromosomes can also undergo horizontal transfer. We combined a directed and a non-biased approach to determine whether such restrictions exist. Selection genes were integrated into the genome of a strain of Fusarium oxysporum pathogenic on tomato, either targeted to specific chromosomes by homologous recombination or integrated randomly into the genome. By testing these strains for transfer of the marker to another strain we could confirm transfer of a previously described mobile pathogenicity chromosome. Surprisingly, we also identified strains in which (parts of) core chromosomes were transferred. Whole genome sequencing revealed that this was accompanied by the loss of the homologous region from the recipient strain. Remarkably, transfer of the mobile pathogenicity chromosome always accompanied this exchange of core chromosomes. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  16. Parallel and lineage-specific molecular adaptation to climate in boreal black spruce.

    Science.gov (United States)

    Prunier, Julien; Gérardi, Sébastien; Laroche, Jérôme; Beaulieu, Jean; Bousquet, Jean

    2012-09-01

    In response to selective pressure, adaptation may follow different genetic pathways throughout the natural range of a species due to historical differentiation in standing genetic variation. Using 41 populations of black spruce (Picea mariana), the objectives of this study were to identify adaptive genetic polymorphisms related to temperature and precipitation variation across the transcontinental range of the species, and to evaluate the potential influence of historical events on their geographic distribution. Population structure was first inferred using 50 control nuclear markers. Then, 47 candidate gene SNPs identified in previous genome scans were tested for relationship with climatic factors using an F(ST) -based outlier method and regressions between allele frequencies and climatic variations. Two main intraspecific lineages related to glacial vicariance were detected at the transcontinental scale. Within-lineage analyses of allele frequencies allowed the identification of 23 candidate SNPs significantly related to precipitation and/or temperature variation, among which seven were common to both lineages, eight were specific to the eastern lineage and eight were specific to the western lineage. The implication of these candidate SNPs in adaptive processes was further supported by gene functional annotations. Multiple evidences indicated that the occurrence of lineage-specific adaptive SNPs was better explained by selection acting on historically differentiated gene pools rather than differential selection due to heterogeneity of interacting environmental factors and pleiotropic effects. Taken together, these findings suggest that standing genetic variation of potentially adaptive nature has been modified by historical events, hence affecting the outcome of recent selection and leading to different adaptive routes between intraspecific lineages. © 2012 Blackwell Publishing Ltd.

  17. Understanding the Molecular Circuitry of Cell Lineage Specification in the Early Mouse Embryo

    Science.gov (United States)

    Bergsmedh, Anna; Donohoe, Mary E.; Hughes, Rebecca-Ayme; Hadjantonakis, Anna-Katerina

    2011-01-01

    Pluripotent stem cells hold great promise for cell-based therapies in regenerative medicine. However, critical to understanding and exploiting mechanisms of cell lineage specification, epigenetic reprogramming, and the optimal environment for maintaining and differentiating pluripotent stem cells is a fundamental knowledge of how these events occur in normal embryogenesis. The early mouse embryo has provided an excellent model to interrogate events crucial in cell lineage commitment and plasticity, as well as for embryo-derived lineage-specific stem cells and induced pluripotent stem (iPS) cells. Here we provide an overview of cell lineage specification in the early (preimplantation) mouse embryo focusing on the transcriptional circuitry and epigenetic marks necessary for successive differentiation events leading to the formation of the blastocyst. PMID:24710206

  18. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.

    Science.gov (United States)

    Lasko, Loren M; Jakob, Clarissa G; Edalji, Rohinton P; Qiu, Wei; Montgomery, Debra; Digiammarino, Enrico L; Hansen, T Matt; Risi, Roberto M; Frey, Robin; Manaves, Vlasios; Shaw, Bailin; Algire, Mikkel; Hessler, Paul; Lam, Lloyd T; Uziel, Tamar; Faivre, Emily; Ferguson, Debra; Buchanan, Fritz G; Martin, Ruth L; Torrent, Maricel; Chiang, Gary G; Karukurichi, Kannan; Langston, J William; Weinert, Brian T; Choudhary, Chunaram; de Vries, Peter; Van Drie, John H; McElligott, David; Kesicki, Ed; Marmorstein, Ronen; Sun, Chaohong; Cole, Philip A; Rosenberg, Saul H; Michaelides, Michael R; Lai, Albert; Bromberg, Kenneth D

    2017-10-05

    The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

  19. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lasko, Loren M.; Jakob, Clarissa G.; Edalji, Rohinton P.; Qiu, Wei; Montgomery, Debra; Digiammarino, Enrico L.; Hansen, T. Matt; Risi, Roberto M.; Frey, Robin; Manaves, Vlasios; Shaw, Bailin; Algire, Mikkel; Hessler, Paul; Lam, Lloyd T.; Uziel, Tamar; Faivre, Emily; Ferguson, Debra; Buchanan, Fritz G.; Martin, Ruth L.; Torrent, Maricel; Chiang, Gary G.; Karukurichi, Kannan; Langston, J. William; Weinert, Brian T.; Choudhary, Chunaram; de Vries, Peter; Van Drie, John H.; McElligott, David; Kesicki, Ed; Marmorstein, Ronen; Sun, Chaohong; Cole, Philip A.; Rosenberg, Saul H.; Michaelides, Michael R.; Lai, Albert; Bromberg, Kenneth D.

    2017-09-27

    The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription1 and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind2. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer3). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products4, bi-substrate analogues5 and the widely used small molecule C6466,7, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

  20. Exchange of core chromosomes and horizontal transfer of lineage-specific chromosomes in Fusarium oxysporum

    NARCIS (Netherlands)

    Vlaardingerbroek, I.; Beerens, B.; Rose, L.; Fokkens, L.; Cornelissen, B.J.C.; Rep, M.

    2016-01-01

    Horizontal transfer of supernumerary or lineage-specific (LS) chromosomes has been described in a number of plant pathogenic filamentous fungi. So far it was not known whether transfer is restricted to chromosomes of certain size or properties, or whether 'core' chromosomes can also undergo

  1. GEISHA: an evolving gene expression resource for the chicken embryo.

    Science.gov (United States)

    Antin, Parker B; Yatskievych, Tatiana A; Davey, Sean; Darnell, Diana K

    2014-01-01

    GEISHA (Gallus Expression In Situ Hybridization Analysis; http://geisha.arizona.edu) is an in situ hybridization gene expression and genomic resource for the chicken embryo. This update describes modifications that enhance its utility to users. During the past 5 years, GEISHA has undertaken a significant restructuring to more closely conform to the data organization and formatting of Model Organism Databases in other species. This has involved migrating from an entry-centric format to one that is gene-centered. Database restructuring has enabled the inclusion of data pertaining to chicken genes and proteins and their orthologs in other species. This new information is presented through an updated user interface. In situ hybridization data in mouse, frog, zebrafish and fruitfly are integrated with chicken genomic and expression information. A resource has also been developed that integrates the GEISHA interface information with the Online Mendelian Inheritance in Man human disease gene database. Finally, the Chicken Gene Nomenclature Committee database and the GEISHA database have been integrated so that they draw from the same data resources.

  2. A Brief History of APOL1: A Gene Evolving.

    Science.gov (United States)

    Friedman, David J

    2017-11-01

    APOL1 kidney risk variants lead to high rates of kidney disease in people of recent African ancestry. These risk variants are very common and confer a large increase in risk of kidney disease. This unusual combination of high frequency and large effect size occurs because the risk variants also appear to have beneficial properties. The risk variants show enhanced protective effects against certain pathogens, particularly the trypanosomes that cause African sleeping sickness. Here, we consider the origins and evolution of the primate-only APOL1 gene. Human genetics, mouse models, biochemistry, and comparative genomics suggest that APOL1 is an innate immunity gene and that the risk variants have the potential for heightened immunity that comes at the cost of toxicity to the kidneys. A better understanding of the evolution of APOL1 may help illuminate how APOL1 causes kidney disease in individuals who harbor the high-risk variants. Copyright © 2017. Published by Elsevier Inc.

  3. The monocytic lineage specific soluble CD163 is a plasma marker of coronary atherosclerosis

    DEFF Research Database (Denmark)

    Aristoteli, Lina Panayiota; Møller, Holger Jon; Bailey, Brian

    2006-01-01

    BACKGROUND: CD163 is a monocyte-macrophage lineage specific scavenger receptor that mediates the uptake and clearance of haptoglobin-haemoglobin complexes, and soluble CD163 (sCD163) is also present in plasma. As atherosclerosis involves infiltration by monocyte-derived macrophages, we investigated...... whether sCD163 may act as a marker of coronary atherosclerosis (CAD). METHODS AND RESULTS: Clinical features were identified and plasma was collected from 147 consecutive patients presenting for coronary angiography. Patients were classified as having CAD+, or being free of CAD- haemodynamically...

  4. Interrogating eleven fast-evolving genes for signatures of recent positive selection in worldwide human populations

    OpenAIRE

    Moreno Estrada, Andrés; Bosch Fusté, Elena; Stoneking, Mark; Bertranpetit, Jaume, 1952-; Calafell i Majó, Francesc; Navarro i Cuartiellas, Arcadi, 1969-; Casals López, Ferran; Tang, Kun; Marquès i Bonet, Tomàs, 1975-; Sikora, Martin, 1976-

    2009-01-01

    Different signatures of natural selection persist over varying time scales in our genome, revealing possible episodes of adaptative evolution during human history. Here, we identify genes showing signatures of ancestral positive selection in the human lineage and investigate whether some of those genes have been evolving adaptatively in extant human populations. Specifically, we compared more than 11,000 human genes with their orthologs in/nchimpanzee, mouse, rat and dog and applied a branch-...

  5. A plant virus evolved by acquiring multiple nonconserved genes to extend its host range.

    Science.gov (United States)

    Tatineni, Satyanarayana; Robertson, Cecile J; Garnsey, Stephen M; Dawson, William O

    2011-10-18

    Viruses have evolved as combinations of genes whose products interact with cellular components to produce progeny virus throughout the plants. Some viral genes, particularly those that are involved in replication and assembly, tend to be relatively conserved, whereas other genes that have evolved for interactions with the specific host for movement and to counter host-defense systems tend to be less conserved. Closteroviridae encode 1-5 nonconserved ORFs. Citrus tristeza virus (CTV), a Closterovirus, possesses nonconserved p33, p18, and p13 genes that are expendable for systemic infection of the two laboratory hosts, Citrus macrophylla and Mexican lime. In this study, we show that the extended host range of CTV requires these nonconserved genes. The p33 gene was required to systemically infect sour orange and lemon trees, whereas either the p33 or the p18 gene was sufficient for systemic infection of grapefruit trees and the p33 or the p13 gene was sufficient for systemic infection of calamondin plants. Thus, these three genes are required for systemic infection of the full host range of CTV, but different genes were specific for different hosts. Remarkably, either of two genes was sufficient for infection of some citrus hybrids. These findings suggest that CTV acquired multiple nonconserved genes (p33, p18, and p13) and, as a result, gained the ability to interact with multiple hosts, thus extending its host range during the course of evolution. These results greatly extend the complexity of known virus-plant interactions.

  6. A plant virus evolved by acquiring multiple nonconserved genes to extend its host range

    Science.gov (United States)

    Tatineni, Satyanarayana; Robertson, Cecile J.; Garnsey, Stephen M.; Dawson, William O.

    2011-01-01

    Viruses have evolved as combinations of genes whose products interact with cellular components to produce progeny virus throughout the plants. Some viral genes, particularly those that are involved in replication and assembly, tend to be relatively conserved, whereas other genes that have evolved for interactions with the specific host for movement and to counter host–defense systems tend to be less conserved. Closteroviridae encode 1–5 nonconserved ORFs. Citrus tristeza virus (CTV), a Closterovirus, possesses nonconserved p33, p18, and p13 genes that are expendable for systemic infection of the two laboratory hosts, Citrus macrophylla and Mexican lime. In this study, we show that the extended host range of CTV requires these nonconserved genes. The p33 gene was required to systemically infect sour orange and lemon trees, whereas either the p33 or the p18 gene was sufficient for systemic infection of grapefruit trees and the p33 or the p13 gene was sufficient for systemic infection of calamondin plants. Thus, these three genes are required for systemic infection of the full host range of CTV, but different genes were specific for different hosts. Remarkably, either of two genes was sufficient for infection of some citrus hybrids. These findings suggest that CTV acquired multiple nonconserved genes (p33, p18, and p13) and, as a result, gained the ability to interact with multiple hosts, thus extending its host range during the course of evolution. These results greatly extend the complexity of known virus–plant interactions. PMID:21987809

  7. Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

    Science.gov (United States)

    Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M.; Miller, Tyler E.; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.; Bredel, Markus

    2014-01-01

    Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

  8. New insights in the clockwork mechanism regulating lineage specification: Lessons from the Drosophila nervous system.

    Science.gov (United States)

    Cattenoz, Pierre B; Giangrande, Angela

    2015-03-01

    Powerful transcription factors called fate determinants induce robust differentiation programs in multipotent cells and trigger lineage specification. These factors guarantee the differentiation of specific tissues/organs/cells at the right place and the right moment to form a fully functional organism. Fate determinants are activated by temporal, positional, epigenetic, and post-transcriptional cues, hence integrating complex and dynamic developmental networks. In turn, they activate specific transcriptional/epigenetic programs that secure novel molecular landscapes. In this review, we use the Drosophila Gcm glial determinant as a model to discuss the mechanisms that allow lineage specification in the nervous system. The dynamic regulation of Gcm via interlocked loops has recently emerged as a key event in the establishment of stable identity. Gcm induces gliogenesis while triggering its own extinction, thus preventing the appearance of metastable states and neoplastic processes. Using simple animal models that allow in vivo manipulations provides a key tool to disentangle the complex regulation of cell fate determinants. © 2014 Wiley Periodicals, Inc.

  9. Cloning of novel rice blast resistance genes from two rapidly evolving NBS-LRR gene families in rice.

    Science.gov (United States)

    Guo, Changjiang; Sun, Xiaoguang; Chen, Xiao; Yang, Sihai; Li, Jing; Wang, Long; Zhang, Xiaohui

    2016-01-01

    Most rice blast resistance genes (R-genes) encode proteins with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains. Our previous study has shown that more rice blast R-genes can be cloned in rapidly evolving NBS-LRR gene families. In the present study, two rapidly evolving R-gene families in rice were selected for cloning a subset of genes from their paralogs in three resistant rice lines. A total of eight functional blast R-genes were identified among nine NBS-LRR genes, and some of these showed resistance to three or more blast strains. Evolutionary analysis indicated that high nucleotide diversity of coding regions served as important parameters in the determination of gene resistance. We also observed that amino-acid variants (nonsynonymous mutations, insertions, or deletions) in essential motifs of the NBS domain contribute to the blast resistance capacity of NBS-LRR genes. These results suggested that the NBS regions might also play an important role in resistance specificity determination. On the other hand, different splicing patterns of introns were commonly observed in R-genes. The results of the present study contribute to improving the effectiveness of R-gene identification by using evolutionary analysis method and acquisition of novel blast resistance genes.

  10. How Genes Evolve Molecular Techniques Give Us a Closer Look at ...

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 2. How Genes Evolve Molecular Techniques Give Us a Closer Look at Evolution at the DNA Level. Ravi Parkash. General Article Volume 3 Issue 2 February 1998 pp 28-34 ...

  11. Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer

    Science.gov (United States)

    Kwei, KA; Kim, YH; Girard, L; Kao, J; Pacyna-Gengelbach, M; Salari, K; Lee, J; Choi, Y-L; Sato, M; Wang, P; Hernandez-Boussard, T; Gazdar, AF; Petersen, I; Minna, JD; Pollack, JR

    2009-01-01

    Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal DNA amplification at cytoband 14q13.3, a locus not amplified in other tumor types. The smallest region of recurrent amplification spanned the homeobox transcription factor TITF1 (thyroid transcription factor 1; also called NKX2-1), previously linked to normal lung development and function. When amplified, TITF1 exhibited increased expression at both the RNA and protein levels. Small interfering RNA (siRNA)- mediated knockdown of TITF1 in lung cancer cell lines with amplification led to reduced cell proliferation, manifested by both decreased cell-cycle progression and increased apoptosis. Our findings indicate that TITF1 amplification and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer. PMID:18212743

  12. Lineage-Specific Changes in Biomarkers in Great Apes and Humans.

    Science.gov (United States)

    Ronke, Claudius; Dannemann, Michael; Halbwax, Michel; Fischer, Anne; Helmschrodt, Christin; Brügel, Mathias; André, Claudine; Atencia, Rebeca; Mugisha, Lawrence; Scholz, Markus; Ceglarek, Uta; Thiery, Joachim; Pääbo, Svante; Prüfer, Kay; Kelso, Janet

    2015-01-01

    Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1), the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans.

  13. Lineage-Specific Changes in Biomarkers in Great Apes and Humans.

    Directory of Open Access Journals (Sweden)

    Claudius Ronke

    Full Text Available Although human biomedical and physiological information is readily available, such information for great apes is limited. We analyzed clinical chemical biomarkers in serum samples from 277 wild- and captive-born great apes and from 312 healthy human volunteers as well as from 20 rhesus macaques. For each individual, we determined a maximum of 33 markers of heart, liver, kidney, thyroid and pancreas function, hemoglobin and lipid metabolism and one marker of inflammation. We identified biomarkers that show differences between humans and the great apes in their average level or activity. Using the rhesus macaques as an outgroup, we identified human-specific differences in the levels of bilirubin, cholinesterase and lactate dehydrogenase, and bonobo-specific differences in the level of apolipoprotein A-I. For the remaining twenty-nine biomarkers there was no evidence for lineage-specific differences. In fact, we find that many biomarkers show differences between individuals of the same species in different environments. Of the four lineage-specific biomarkers, only bilirubin showed no differences between wild- and captive-born great apes. We show that the major factor explaining the human-specific difference in bilirubin levels may be genetic. There are human-specific changes in the sequence of the promoter and the protein-coding sequence of uridine diphosphoglucuronosyltransferase 1 (UGT1A1, the enzyme that transforms bilirubin and toxic plant compounds into water-soluble, excretable metabolites. Experimental evidence that UGT1A1 is down-regulated in the human liver suggests that changes in the promoter may be responsible for the human-specific increase in bilirubin. We speculate that since cooking reduces toxic plant compounds, consumption of cooked foods, which is specific to humans, may have resulted in relaxed constraint on UGT1A1 which has in turn led to higher serum levels of bilirubin in humans.

  14. Environmental noise, genetic diversity and the evolution of evolvability and robustness in model gene networks.

    Directory of Open Access Journals (Sweden)

    Christopher F Steiner

    Full Text Available The ability of organisms to adapt and persist in the face of environmental change is accepted as a fundamental feature of natural systems. More contentious is whether the capacity of organisms to adapt (or "evolvability" can itself evolve and the mechanisms underlying such responses. Using model gene networks, I provide evidence that evolvability emerges more readily when populations experience positively autocorrelated environmental noise (red noise compared to populations in stable or randomly varying (white noise environments. Evolvability was correlated with increasing genetic robustness to effects on network viability and decreasing robustness to effects on phenotypic expression; populations whose networks displayed greater viability robustness and lower phenotypic robustness produced more additive genetic variation and adapted more rapidly in novel environments. Patterns of selection for robustness varied antagonistically with epistatic effects of mutations on viability and phenotypic expression, suggesting that trade-offs between these properties may constrain their evolutionary responses. Evolution of evolvability and robustness was stronger in sexual populations compared to asexual populations indicating that enhanced genetic variation under fluctuating selection combined with recombination load is a primary driver of the emergence of evolvability. These results provide insight into the mechanisms potentially underlying rapid adaptation as well as the environmental conditions that drive the evolution of genetic interactions.

  15. Horizontal gene transfer: essentiality and evolvability in prokaryotes, and roles in evolutionary transitions

    Science.gov (United States)

    Koonin, Eugene V.

    2016-01-01

    The wide spread of gene exchange and loss in the prokaryotic world has prompted the concept of ‘lateral genomics’ to the point of an outright denial of the relevance of phylogenetic trees for evolution. However, the pronounced coherence congruence of the topologies of numerous gene trees, particularly those for (nearly) universal genes, translates into the notion of a statistical tree of life (STOL), which reflects a central trend of vertical evolution. The STOL can be employed as a framework for reconstruction of the evolutionary processes in the prokaryotic world. Quantitatively, however, horizontal gene transfer (HGT) dominates microbial evolution, with the rate of gene gain and loss being comparable to the rate of point mutations and much greater than the duplication rate. Theoretical models of evolution suggest that HGT is essential for the survival of microbial populations that otherwise deteriorate due to the Muller’s ratchet effect. Apparently, at least some bacteria and archaea evolved dedicated vehicles for gene transfer that evolved from selfish elements such as plasmids and viruses. Recent phylogenomic analyses suggest that episodes of massive HGT were pivotal for the emergence of major groups of organisms such as multiple archaeal phyla as well as eukaryotes. Similar analyses appear to indicate that, in addition to donating hundreds of genes to the emerging eukaryotic lineage, mitochondrial endosymbiosis severely curtailed HGT. These results shed new light on the routes of evolutionary transitions, but caution is due given the inherent uncertainty of deep phylogenies. PMID:27508073

  16. Horizontal gene transfer: essentiality and evolvability in prokaryotes, and roles in evolutionary transitions.

    Science.gov (United States)

    Koonin, Eugene V

    2016-01-01

    The wide spread of gene exchange and loss in the prokaryotic world has prompted the concept of 'lateral genomics' to the point of an outright denial of the relevance of phylogenetic trees for evolution. However, the pronounced coherence congruence of the topologies of numerous gene trees, particularly those for (nearly) universal genes, translates into the notion of a statistical tree of life (STOL), which reflects a central trend of vertical evolution. The STOL can be employed as a framework for reconstruction of the evolutionary processes in the prokaryotic world. Quantitatively, however, horizontal gene transfer (HGT) dominates microbial evolution, with the rate of gene gain and loss being comparable to the rate of point mutations and much greater than the duplication rate. Theoretical models of evolution suggest that HGT is essential for the survival of microbial populations that otherwise deteriorate due to the Muller's ratchet effect. Apparently, at least some bacteria and archaea evolved dedicated vehicles for gene transfer that evolved from selfish elements such as plasmids and viruses. Recent phylogenomic analyses suggest that episodes of massive HGT were pivotal for the emergence of major groups of organisms such as multiple archaeal phyla as well as eukaryotes. Similar analyses appear to indicate that, in addition to donating hundreds of genes to the emerging eukaryotic lineage, mitochondrial endosymbiosis severely curtailed HGT. These results shed new light on the routes of evolutionary transitions, but caution is due given the inherent uncertainty of deep phylogenies.

  17. Rodent-specific alternative exons are more frequent in rapidly evolving genes and in paralogs

    Directory of Open Access Journals (Sweden)

    Mironov Andrey A

    2009-06-01

    Full Text Available Abstract Background Alternative splicing is an important mechanism for generating functional and evolutionary diversity of proteins in eukaryotes. Here, we studied the frequency and functionality of recently gained, rodent-specific alternative exons. Results We projected the data about alternative splicing of mouse genes to the rat, human, and dog genomes, and identified exons conserved in the rat genome, but missing in more distant genomes. We estimated the frequency of rodent-specific exons while controlling for possible residual conservation of spurious exons. The frequency of rodent-specific exons is higher among predominantly skipped exons and exons disrupting the reading frame. Separation of all genes by the rate of sequence evolution and by gene families has demonstrated that rodent-specific cassette exons are more frequent in rapidly evolving genes and in rodent-specific paralogs. Conclusion Thus we demonstrated that recently gained exons tend to occur in fast-evolving genes, and their inclusion rate tends to be lower than that of older exons. This agrees with the theory that gain of alternative exons is one of the major mechanisms of gene evolution.

  18. Lineage specific evolution of the VNTR composite retrotransposon central domain and its role in retrotransposition of gibbon LAVA elements.

    Science.gov (United States)

    Lupan, Iulia; Bulzu, Paul; Popescu, Octavian; Damert, Annette

    2015-05-16

    VNTR (Variable Number of Tandem Repeats) composite retrotransposons - SVA (SINE-R-VNTR-Alu), LAVA (LINE-1-Alu-VNTR-Alu), PVA (PTGR2-VNTR-Alu) and FVA (FRAM-VNTR-Alu) - are specific to hominoid primates. Their assembly, the evolution of their 5' and 3' domains, and the functional significance of the shared 5' Alu-like region are well understood. The central VNTR domain, by contrast, has long been assumed to represent a more or less random collection of 30-50 bp GC-rich repeats. It is only recently that it attracted attention in the context of regulation of SVA expression. Here we provide evidence that the organization of the VNTR is non-random, with conserved repeat unit (RU) arrays at both the 5' and 3' ends of the VNTRs of human, chimpanzee and orangutan SVA and gibbon LAVA. The younger SVA subfamilies harbour highly organized internal RU arrays. The composition of these arrays is specific to the human/chimpanzee and orangutan lineages, respectively. Tracing the development of the VNTR through evolution we show for the first time how tandem repeats evolve within the constraints set by a functional, non-autonomous non-LTR retrotransposon in two different families - LAVA and SVA - in different hominoid lineages. Our analysis revealed that a microhomology-driven mechanism mediates expansion/contraction of the VNTR domain at the DNA level. Elements of all four VNTR composite families have been shown to be mobilized by the autonomous LINE1 retrotransposon in trans. In case of SVA, key determinants of mobilization are found in the 5' hexameric repeat/Alu-like region. We now demonstrate that in LAVA, by contrast, the VNTR domain determines mobilization efficiency in the context of domain swaps between active and inactive elements. The central domain of VNTR composites evolves in a lineage-specific manner which gives rise to distinct structures in gibbon LAVA, orangutan SVA, and human/chimpanzee SVA. The differences observed between the families and lineages are likely to

  19. Lineage Specification from Prostate Progenitor Cells Requires Gata3-Dependent Mitotic Spindle Orientation.

    Science.gov (United States)

    Shafer, Maxwell E R; Nguyen, Alana H T; Tremblay, Mathieu; Viala, Sophie; Béland, Mélanie; Bertos, Nicholas R; Park, Morag; Bouchard, Maxime

    2017-04-11

    During prostate development, basal and luminal cell lineages are generated through symmetric and asymmetric divisions of bipotent basal cells. However, the extent to which spindle orientation controls division symmetry or cell fate, and the upstream factors regulating this process, are still elusive. We report that GATA3 is expressed in both prostate basal progenitor and luminal cells and that loss of GATA3 leads to a mislocalization of PRKCZ, resulting in mitotic spindle randomization during progenitor cell division. Inherently proliferative intermediate progenitor cells accumulate, leading to an expansion of the luminal compartment. These defects ultimately result in a loss of tissue polarity and defective branching morphogenesis. We further show that disrupting the interaction between PRKCZ and PARD6B is sufficient to recapitulate the spindle and cell lineage phenotypes. Collectively, these results identify a critical role for GATA3 in prostate lineage specification, and further highlight the importance of regulating spindle orientation for hierarchical cell lineage organization. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. Depletion of Suds3 reveals an essential role in early lineage specification.

    Science.gov (United States)

    Zhang, Kun; Dai, Xiangpeng; Wallingford, Mary C; Mager, Jesse

    2013-01-15

    Preimplantation development culminates with the emergence of three distinct populations: the inner cell mass, primitive endoderm and trophectoderm. Here, we define the mechanisms underlying the requirement of Suds3 in pre/peri-implantation development. Suds3 knockdown blastocysts exhibit a failure of both trophectoderm proliferation as well as a conspicuous lack of primitive endoderm. Expression of essential lineage factors Nanog, Sox2, Cdx2, Eomes, Elf5 and Sox17 are severely reduced in the absence of Suds3. Importantly, we document deficient FGF4/ERK signaling and show that exogenous FGF4 rescues primitive endoderm formation and trophectoderm proliferation in Suds3 knockdown blastocysts. We also show that Hdac1 knockdown reduces Sox2/FGF4/ERK signaling in blastocysts. Collectively, these data define a role for Suds3 in activation of FGF4/ERK signaling and determine an essential molecular role of Suds3/Sin3/HDAC complexes in lineage specification in vivo. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Lineage specification of parietal epithelial cells requires β-catenin/Wnt signaling.

    Science.gov (United States)

    Grouls, Stephan; Iglesias, Diana Margarita; Wentzensen, Nicolas; Moeller, Marcus Johannes; Bouchard, Maxime; Kemler, Rolf; Goodyer, Paul; Niggli, Felix; Gröne, Hermann-Josef; Kriz, Wilhelm; Koesters, Robert

    2012-01-01

    β-Catenin/Wnt signaling is essential during early inductive stages of kidney development, but its role during postinductive stages of nephron development and maturation is not well understood. In this study, we used Pax8Cre mice to target β-catenin deficiency to renal epithelial cells at the late S-shaped body stage and the developing collecting ducts. The conditional β-catenin knockout mice formed abnormal kidneys and had reduced renal function. The kidneys were hypoplastic with a thin cortex; a superficial layer of tubules was missing. A high proportion of glomeruli had small, underdeveloped capillary tufts. In these glomeruli, well differentiated podocytes replaced parietal epithelial cells in Bowman's capsule; capillaries toward the outer aspect of these podocytes mimicked the formation of glomerular capillaries. Tracing nephrogenesis in embryonic conditional β-catenin knockout mice revealed that these "parietal podocytes" derived from precursor cells in the parietal layer of the S-shaped body by direct lineage switch. Taken together, these findings demonstrate that β-catenin/Wnt signaling is important during the late stages of nephrogenesis and for the lineage specification of parietal epithelial cells.

  3. The impact of gene expression variation on the robustness and evolvability of a developmental gene regulatory network.

    Directory of Open Access Journals (Sweden)

    David A Garfield

    2013-10-01

    Full Text Available Regulatory interactions buffer development against genetic and environmental perturbations, but adaptation requires phenotypes to change. We investigated the relationship between robustness and evolvability within the gene regulatory network underlying development of the larval skeleton in the sea urchin Strongylocentrotus purpuratus. We find extensive variation in gene expression in this network throughout development in a natural population, some of which has a heritable genetic basis. Switch-like regulatory interactions predominate during early development, buffer expression variation, and may promote the accumulation of cryptic genetic variation affecting early stages. Regulatory interactions during later development are typically more sensitive (linear, allowing variation in expression to affect downstream target genes. Variation in skeletal morphology is associated primarily with expression variation of a few, primarily structural, genes at terminal positions within the network. These results indicate that the position and properties of gene interactions within a network can have important evolutionary consequences independent of their immediate regulatory role.

  4. Hominoid lineage specific amplification of low-copy repeats on 22q11.2 (LCR22s) associated with velo-cardio-facial/digeorge syndrome.

    Science.gov (United States)

    Babcock, Melanie; Yatsenko, Svetlana; Hopkins, Janet; Brenton, Matthew; Cao, Qing; de Jong, Pieter; Stankiewicz, Pawel; Lupski, James R; Sikela, James M; Morrow, Bernice E

    2007-11-01

    Segmental duplications or low-copy repeats (LCRs) constitute approximately 5% of the sequenced portion of the human genome and are associated with many human congenital anomaly disorders. The low-copy repeats on chromosome 22q11.2 (LCR22s) mediate chromosomal rearrangements resulting in deletions, duplications and translocations. The evolutionary mechanisms leading to LCR22 formation is unknown. Four genes, USP18, BCR, GGTLA and GGT, map adjacent to the LCR22s and pseudogene copies are located within them. It has been hypothesized that gene duplication occurred during primate evolution, followed by recombination events, forming pseudogene copies. We investigated whether gene duplication could be detected in non-human hominoid species. FISH mapping was performed using probes to the four functional gene loci. There was evidence for a single copy in humans but additional copies in hominoid species. We then compared LCR22 copy number using LCR22 FISH probes. Lineage specific LCR22 variation was detected in the hominoid species supporting the hypothesis. To independently validate initial findings, real time PCR, and screening of gorilla BAC library filters were performed. This was compared to array comparative genome hybridization data available. The most striking finding was a dramatic amplification of LCR22s in the gorilla. The LCR22s localized to the telomeric or subtelomeric bands of gorilla chromosomes. The most parsimonious explanation is that the LCR22s became amplified by inter-chromosomal recombination between telomeric bands. In summary, our results are consistent with a lineage specific coupling between gene and LCR22 duplication events. The LCR22s thus serve as an important model for evolution of genome variation.

  5. Mycobacterium tuberculosis Complex Exhibits Lineage-Specific Variations Affecting Protein Ductility and Epitope Recognition

    Science.gov (United States)

    Yruela, Inmaculada; Contreras-Moreira, Bruno; Magalhães, Carlos; Osório, Nuno S.

    2016-01-01

    Abstract The advent of whole-genome sequencing has provided an unprecedented detail about the evolution and genetic significance of species-specific variations across the whole Mycobacterium tuberculosis Complex. However, little attention has been focused on understanding the functional roles of these variations in the protein coding sequences. In this work, we compare the coding sequences from 74 sequenced mycobacterial species including M. africanum, M. bovis, M. canettii, M. caprae, M. orygis, and M. tuberculosis. Results show that albeit protein variations affect all functional classes, those proteins involved in lipid and intermediary metabolism and respiration have accumulated mutations during evolution. To understand the impact of these mutations on protein functionality, we explored their implications on protein ductility/disorder, a yet unexplored feature of mycobacterial proteomes. In agreement with previous studies, we found that a Gly71Ile substitution in the PhoPR virulence system severely affects the ductility of its nearby region in M. africanum and animal-adapted species. In the same line of evidence, the SmtB transcriptional regulator shows amino acid variations specific to the Beijing lineage, which affects the flexibility of the N-terminal trans-activation domain. Furthermore, despite the fact that MTBC epitopes are evolutionary hyperconserved, we identify strain- and lineage-specific amino acid mutations affecting previously known T-cell epitopes such as EsxH and FbpA (Ag85A). Interestingly, in silico studies reveal that these variations result in differential interaction of epitopes with the main HLA haplogroups. PMID:28062754

  6. Exploiting Heparan Sulfate Proteoglycans in Human Neurogenesis—Controlling Lineage Specification and Fate

    Directory of Open Access Journals (Sweden)

    Chieh Yu

    2017-10-01

    lineage fate and produce abundant cells of lineage specificity will further advance stem cell therapy for the development of improved repair of neurological disorders. We propose a deeper understanding of HSPG-mediated neurogenesis can potentially provide novel therapeutic targets of neurogenesis.

  7. "Evolving nanoparticle gene delivery vectors for the liver: What has been learned in 30 years".

    Science.gov (United States)

    Crowley, Samuel T; Rice, Kevin G

    2015-12-10

    Nonviral gene delivery to the liver has been under evolution for nearly 30years. Early demonstrations established relatively simple nonviral vectors could mediate gene expression in HepG2 cells which understandably led to speculation that these same vectors would be immediately successful at transfecting primary hepatocytes in vivo. However, it was soon recognized that the properties of a nonviral vector resulting in efficient transfection in vitro were uncorrelated with those needed to achieve efficient nonviral transfection in vivo. The discovery of major barriers to liver gene transfer has set the field on a course to design biocompatible vectors that demonstrate increased DNA stability in the circulation with correlating expression in liver. The improved understanding of what limits nonviral vector gene transfer efficiency in vivo has resulted in more sophisticated, low molecular weight vectors that allow systematic optimization of nanoparticle size, charge and ligand presentation. While the field has evolved DNA nanoparticles that are stable in the circulation, target hepatocytes, and deliver DNA to the cytosol, breaching the nucleus remains the last major barrier to a fully successful nonviral gene transfer system for the liver. The lessons learned along the way are fundamentally important to the design of all systemically delivered nanoparticle nonviral gene delivery systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Cell lineage specific distribution of H3K27 trimethylation accumulation in an in vitro model for human implantation.

    Directory of Open Access Journals (Sweden)

    Gijs Teklenburg

    Full Text Available Female mammals inactivate one of their two X-chromosomes to compensate for the difference in gene-dosage with males that have just one X-chromosome. X-chromosome inactivation is initiated by the expression of the non-coding RNA Xist, which coats the X-chromosome in cis and triggers gene silencing. In early mouse development the paternal X-chromosome is initially inactivated in all cells of cleavage stage embryos (imprinted X-inactivation followed by reactivation of the inactivated paternal X-chromosome exclusively in the epiblast precursors of blastocysts, resulting temporarily in the presence of two active X-chromosomes in this specific lineage. Shortly thereafter, epiblast cells randomly inactivate either the maternal or the paternal X-chromosome. XCI is accompanied by the accumulation of histone 3 lysine 27 trimethylation (H3K27me3 marks on the condensed X-chromosome. It is still poorly understood how XCI is regulated during early human development. Here we have investigated lineage development and the distribution of H3K27me3 foci in human embryos derived from an in-vitro model for human implantation. In this system, embryos are co-cultured on decidualized endometrial stromal cells up to day 8, which allows the culture period to be extended for an additional two days. We demonstrate that after the co-culture period, the inner cell masses have relatively high cell numbers and that the GATA4-positive hypoblast lineage and OCT4-positive epiblast cell lineage in these embryos have segregated. H3K27me3 foci were observed in ∼25% of the trophectoderm cells and in ∼7.5% of the hypoblast cells, but not in epiblast cells. In contrast with day 8 embryos derived from the co-cultures, foci of H3K27me3 were not observed in embryos at day 5 of development derived from regular IVF-cultures. These findings indicate that the dynamics of H3K27me3 accumulation on the X-chromosome in human development is regulated in a lineage specific fashion.

  9. Identification of fast-evolving genes in the scleractinian coral Acropora using comparative EST analysis.

    Directory of Open Access Journals (Sweden)

    Akira Iguchi

    Full Text Available To identify fast-evolving genes in reef-building corals, we performed direct comparative sequence analysis with expressed sequence tag (EST datasets from two acroporid species: Acropora palmata from the Caribbean Sea and A. millepora from the Great Barrier Reef in Australia. Comparison of 589 independent sequences from 1,421 A. palmata contigs, with 10,247 A. millepora contigs resulted in the identification of 196 putative homologues. Most of the homologous pairs demonstrated high amino acid similarities (over 90%. Comparisons of putative homologues showing low amino acid similarities (under 90% among the Acropora species to the near complete datasets from two other cnidarians (Hydra magnipapillata and Nematostella vectensis implied that some were non-orthologous. Within 86 homologous pairs, 39 exhibited dN/dS ratios significantly less than 1, suggesting that these genes are under purifying selection associated with functional constraints. Eight independent genes showed dN/dS ratios exceeding 1, while three deviated significantly from 1, suggesting that these genes may play important roles in the adaptive evolution of Acropora. Our results also indicated that CEL-III lectin was under positive selection, consistent with a possible role in immunity or symbiont recognition. Further studies are needed to clarify the possible functions of the genes under positive selection to provide insight into the evolutionary process of corals.

  10. A cleavage clock regulates features of lineage-specific differentiation in the development of a basal branching metazoan, the ctenophore Mnemiopsis leidyi.

    Science.gov (United States)

    Fischer, Antje Hl; Pang, Kevin; Henry, Jonathan Q; Martindale, Mark Q

    2014-01-31

    ratio, are critical for the appearance of lineage-specific differentiation. Our work corroborates previous studies demonstrating that the cleavage program is causally involved in the spatial segregation and/or activation of factors that give rise to distinct cell types in ctenophore development. These factors are segregated independently to the appropriate lineage at the 8- and the 16-cell stages and have features of a clock, such that comb-plate-like cilia and light-emitting photoproteins appear at roughly the same developmental time in cleavage-arrested embryos as they do in untreated embryos. Nuclear division, which possibly affects DNA-cytoplasmic ratios, appears to be important in the timing of differentiation markers. Evidence suggests that the 60-cell stage, just prior to gastrulation, is the time of zygotic gene activation. Such cleavage-clock-regulated phenomena appear to be widespread amongst the Metazoa and these cellular and molecular developmental mechanisms probably evolved early in metazoan evolution.

  11. Development stage-specific proteomic profiling uncovers small, lineage specific proteins most abundant in the Aspergillus Fumigatus conidial proteome

    Directory of Open Access Journals (Sweden)

    Suh Moo-Jin

    2012-04-01

    housekeeping functions, particularly translation, respiratory metabolism, amino acid and carbohydrate biosynthesis, and the tricarboxylic acid cycle. Conclusions The observed temporal expression patterns suggest that the A. fumigatus conidia are dominated by small, lineage-specific proteins. Some of them may play key roles in host-pathogen interactions, signal transduction during conidial germination, or survival in hostile environments.

  12. Whole genome sequencing of a banana wild relative Musa itinerans provides insights into lineage-specific diversification of the Musa genus.

    Science.gov (United States)

    Wu, Wei; Yang, Yu-Lan; He, Wei-Ming; Rouard, Mathieu; Li, Wei-Ming; Xu, Meng; Roux, Nicolas; Ge, Xue-Jun

    2016-08-17

    Crop wild relatives are valuable resources for future genetic improvement. Here, we report the de novo genome assembly of Musa itinerans, a disease-resistant wild banana relative in subtropical China. The assembled genome size was 462.1 Mb, covering 75.2% of the genome (615.2Mb) and containing 32, 456 predicted protein-coding genes. Since the approximate divergence around 5.8 million years ago, the genomes of Musa itinerans and Musa acuminata have shown conserved collinearity. Gene family expansions and contractions enrichment analysis revealed that some pathways were associated with phenotypic or physiological innovations. These include a transition from wood to herbaceous in the ancestral Musaceae, intensification of cold and drought tolerances, and reduced diseases resistance genes for subtropical marginally distributed Musa species. Prevalent purifying selection and transposed duplications were found to facilitate the diversification of NBS-encoding gene families for two Musa species. The population genome history analysis of M. itinerans revealed that the fluctuated population sizes were caused by the Pleistocene climate oscillations, and that the formation of Qiongzhou Strait might facilitate the population downsizing on the isolated Hainan Island about 10.3 Kya. The qualified assembly of the M. itinerans genome provides deep insights into the lineage-specific diversification and also valuable resources for future banana breeding.

  13. Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies.

    Science.gov (United States)

    Verma, Swati; Soto, Jackeline; Vasudevan, Anupama; Schmeisser, Falko; Alvarado-Facundo, Esmeralda; Wang, Wei; Weiss, Carol D; Weir, Jerry P

    2017-01-01

    Co-circulation of two antigenically and genetically distinct lineages of influenza B virus, represented by prototype viruses B/Victoria/2/1987 and B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines that contain two influenza B antigens. The inclusion of two influenza B antigens presents challenges for the production and regulation of inactivated quadrivalent vaccines, including the potential for cross-reactivity of the reagents used in identity and potency assays because of the relative close relatedness of the hemagglutinin (HA) from the two virus lineages. Monoclonal antibodies (mAbs) specific for the two lineages of influenza B HA were generated and characterized and used to set-up simple identity tests that distinguish the influenza B antigens in inactivated trivalent and quadrivalent vaccines. The lineage-specific mAbs bound well to the HA of influenza B strains included in influenza vaccines over a period of more than 10 years, suggesting that identity tests using such lineage-specific mAbs would not necessarily have to be updated with every influenza B vaccine strain change. These lineage-specific mAbs were also used in an antibody capture ELISA format to quantify HA in vaccine samples, including monovalent, trivalent, and quadrivalent vaccine samples from various manufacturers. The results demonstrated correlation with HA values determined by the traditional single radial immunodiffusion (SRID) assay. Further, the antibody-capture ELISA was able to distinguish heat-stressed vaccine from unstressed vaccine, and was similar to the SRID in quantifying the resultant loss of potency. These mAb reagents should be useful for further development of antibody-based alternative influenza B identity and potency assays.

  14. Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies.

    Directory of Open Access Journals (Sweden)

    Swati Verma

    Full Text Available Co-circulation of two antigenically and genetically distinct lineages of influenza B virus, represented by prototype viruses B/Victoria/2/1987 and B/Yamagata/16/1988, has led to the development of quadrivalent influenza vaccines that contain two influenza B antigens. The inclusion of two influenza B antigens presents challenges for the production and regulation of inactivated quadrivalent vaccines, including the potential for cross-reactivity of the reagents used in identity and potency assays because of the relative close relatedness of the hemagglutinin (HA from the two virus lineages. Monoclonal antibodies (mAbs specific for the two lineages of influenza B HA were generated and characterized and used to set-up simple identity tests that distinguish the influenza B antigens in inactivated trivalent and quadrivalent vaccines. The lineage-specific mAbs bound well to the HA of influenza B strains included in influenza vaccines over a period of more than 10 years, suggesting that identity tests using such lineage-specific mAbs would not necessarily have to be updated with every influenza B vaccine strain change. These lineage-specific mAbs were also used in an antibody capture ELISA format to quantify HA in vaccine samples, including monovalent, trivalent, and quadrivalent vaccine samples from various manufacturers. The results demonstrated correlation with HA values determined by the traditional single radial immunodiffusion (SRID assay. Further, the antibody-capture ELISA was able to distinguish heat-stressed vaccine from unstressed vaccine, and was similar to the SRID in quantifying the resultant loss of potency. These mAb reagents should be useful for further development of antibody-based alternative influenza B identity and potency assays.

  15. Human embryonic stem cells differentiated to lung lineage-specific cells ameliorate pulmonary fibrosis in a xenograft transplant mouse model.

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    Ena Ray Banerjee

    Full Text Available Our aim was to differentiate human (h embryonic stem (ES cells into lung epithelial lineage-specific cells [i.e., alveolar epithelial type I (AEI and type II (AEII cells and Clara cells] as the first step in the development of cell-based strategies to repair lung injury in the bleomycin mouse model of idiopathic pulmonary fibrosis (IPF. A heterogeneous population of non-ciliated lung lineage-specific cells was derived by a novel method of embryoid body (EB differentiation. This differentiated human cell population was used to modulate the profibrotic phenotype in transplanted animals.Omission or inclusion of one or more components in the differentiation medium skewed differentiation of H7 hES cells into varying proportions of AEI, AEII, and Clara cells. ICG-001, a small molecule inhibitor of Wnt/β-catenin/Creb-binding protein (CBP transcription, changed marker expression of the differentiated ES cells from an AEII-like phenotype to a predominantly AEI-like phenotype. The differentiated cells were used in xenograft transplantation studies in bleomycin-treated Rag2γC(-/- mice. Human cells were detected in lungs of the transplanted groups receiving differentiated ES cells treated with or without ICG-001. The increased lung collagen content found in bleomycin-treated mice receiving saline was significantly reduced by transplantation with the lung-lineage specific epithelial cells differentiated from ES cells. A significant increase in progenitor number was observed in the airways of bleomycin-treated mice after transplantation of differentiated hES cells.This study indicates that ES cell-based therapy may be a powerful novel approach to ameliorate lung fibrosis.

  16. Directing lineage specification of human mesenchymal stem cells by decoupling electrical stimulation and physical patterning on unmodified graphene

    Science.gov (United States)

    Balikov, Daniel A.; Fang, Brian; Chun, Young Wook; Crowder, Spencer W.; Prasai, Dhiraj; Lee, Jung Bok; Bolotin, Kiril I.; Sung, Hak-Joon

    2016-07-01

    The organization and composition of the extracellular matrix (ECM) have been shown to impact the propagation of electrical signals in multiple tissue types. To date, many studies with electroactive biomaterial substrates have relied upon passive electrical stimulation of the ionic media to affect cell behavior. However, development of cell culture systems in which stimulation can be directly applied to the material - thereby isolating the signal to the cell-material interface and cell-cell contracts - would provide a more physiologically-relevant paradigm for investigating how electrical cues modulate lineage-specific stem cell differentiation. In the present study, we have employed unmodified, directly-stimulated, (un)patterned graphene as a cell culture substrate to investigate how extrinsic electrical cycling influences the differentiation of naïve human mesenchymal stem cells (hMSCs) without the bias of exogenous biochemicals. We first demonstrated that cyclic stimulation does not deteriorate the cell culture media or result in cytotoxic pH, which are critical experiments for correct interpretation of changes in cell behavior. We then measured how the expression of osteogenic and neurogenic lineage-specific markers were altered simply by exposure to electrical stimulation and/or physical patterns. Expression of the early osteogenic transcription factor RUNX2 was increased by electrical stimulation on all graphene substrates, but the mature marker osteopontin was only modulated when stimulation was combined with physical patterns. In contrast, the expression of the neurogenic markers MAP2 and β3-tubulin were enhanced in all electrical stimulation conditions, and were less responsive to the presence of patterns. These data indicate that specific combinations of non-biological inputs - material type, electrical stimulation, physical patterns - can regulate hMSC lineage specification. This study represents a substantial step in understanding how the interplay of

  17. Evolving gene banks: improving diverse populations of crop and exotic germplasm with optimal contribution selection.

    Science.gov (United States)

    Cowling, W A; Li, L; Siddique, K H M; Henryon, M; Berg, P; Banks, R G; Kinghorn, B P

    2017-04-01

    We simulated pre-breeding in evolving gene banks - populations of exotic and crop types undergoing optimal contribution selection for long-term genetic gain and management of population genetic diversity. The founder population was based on crosses between elite crop varieties and exotic lines of field pea (Pisum sativum) from the primary genepool, and was subjected to 30 cycles of recurrent selection for an economic index composed of four traits with low heritability: black spot resistance, flowering time and stem strength (measured on single plants), and grain yield (measured on whole plots). We compared a small population with low selection pressure, a large population with high selection pressure, and a large population with moderate selection pressure. Single seed descent was compared with S0-derived recurrent selection. Optimal contribution selection achieved higher index and lower population coancestry than truncation selection, which reached a plateau in index improvement after 40 years in the large population with high selection pressure. With optimal contribution selection, index doubled in 38 years in the small population with low selection pressure and 27-28 years in the large population with moderate selection pressure. Single seed descent increased the rate of improvement in index per cycle but also increased cycle time. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  18. Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification.

    Science.gov (United States)

    Wilson, Korey A; Elefanty, Andrew G; Stanley, Edouard G; Gilbert, David M

    2016-09-16

    Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification.

  19. Lineage-specific interface proteins match up the cell cycle and differentiation in embryo stem cells

    DEFF Research Database (Denmark)

    Re, Angela; Workman, Christopher; Waldron, Levi

    2014-01-01

    interaction data. A new class of non-transcriptionally regulated genes was identified, encoding proteins which interact systematically with proteins corresponding to genes regulated during the cell cycle or cell differentiation, and which therefore can be seen as interface proteins coordinating the two...... programs. Functional analysis gathered insights in fate-specific candidates of interface functionalities. The non-transcriptionally regulated interface proteins were found to be highly regulated by post-translational ubiquitylation modification, which may synchronize the transition between cell...... changes during the cell cycle and ESC differentiation by combining four human cell cycle transcriptome profiles with thirteen in vitro human ESC differentiation studies. To detect cross-talk mechanisms we then integrated the transcriptome data that displayed differential regulation with protein...

  20. Genome-Wide Analysis in Three Fusarium Pathogens Identifies Rapidly Evolving Chromosomes and Genes Associated with Pathogenicity

    Science.gov (United States)

    Sperschneider, Jana; Gardiner, Donald M.; Thatcher, Louise F.; Lyons, Rebecca; Singh, Karam B.; Manners, John M.; Taylor, Jennifer M.

    2015-01-01

    Pathogens and hosts are in an ongoing arms race and genes involved in host–pathogen interactions are likely to undergo diversifying selection. Fusarium plant pathogens have evolved diverse infection strategies, but how they interact with their hosts in the biotrophic infection stage remains puzzling. To address this, we analyzed the genomes of three Fusarium plant pathogens for genes that are under diversifying selection. We found a two-speed genome structure both on the chromosome and gene group level. Diversifying selection acts strongly on the dispensable chromosomes in Fusarium oxysporum f. sp. lycopersici and on distinct core chromosome regions in Fusarium graminearum, all of which have associations with virulence. Members of two gene groups evolve rapidly, namely those that encode proteins with an N-terminal [SG]-P-C-[KR]-P sequence motif and proteins that are conserved predominantly in pathogens. Specifically, 29 F. graminearum genes are rapidly evolving, in planta induced and encode secreted proteins, strongly pointing toward effector function. In summary, diversifying selection in Fusarium is strongly reflected as genomic footprints and can be used to predict a small gene set likely to be involved in host–pathogen interactions for experimental verification. PMID:25994930

  1. New Functional Signatures for Understanding Melanoma Biology from Tumor Cell Lineage-Specific Analysis

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    Florian Rambow

    2015-10-01

    Full Text Available Molecular signatures specific to particular tumor types are required to design treatments for resistant tumors. However, it remains unclear whether tumors and corresponding cell lines used for drug development share such signatures. We developed similarity core analysis (SCA, a universal and unsupervised computational framework for extracting core molecular features common to tumors and cell lines. We applied SCA to mRNA/miRNA expression data from various sources, comparing melanoma cell lines and metastases. The signature obtained was associated with phenotypic characteristics in vitro, and the core genes CAPN3 and TRIM63 were implicated in melanoma cell migration/invasion. About 90% of the melanoma signature genes belong to an intrinsic network of transcription factors governing neural development (TFAP2A, DLX2, ALX1, MITF, PAX3, SOX10, LEF1, and GAS7 and miRNAs (211-5p, 221-3p, and 10a-5p. The SCA signature effectively discriminated between two subpopulations of melanoma patients differing in overall survival, and classified MEKi/BRAFi-resistant and -sensitive melanoma cell lines.

  2. Lineage-specific loss of FGF17 within the avian orders Galliformes and Passeriformes.

    Science.gov (United States)

    Abramyan, John

    2015-06-01

    The genomic and developmental complexity of vertebrates is commonly attributed to two rounds of whole genome duplications which occurred at the base of the vertebrate radiation. These duplications led to the rise of several, multi-gene families of developmental proteins like the fibroblast growth factors (FGFs); a signaling protein family which functions at various stages of embryonic development. One of the major FGF assemblages arising from these duplications is the FGF8 subfamily, which includes FGF8, FGF17, and FGF18 in tetrapods. While FGF8 and FGF18 are found in all tetrapods and are critical for embryonic survival, genomic analyses suggest putative loss of FGF17 in various lineages ranging from frogs and fish, to the chicken. This study utilizes 27 avian genomes in conjunction with molecular analyses of chicken embryos to confirm the loss of FGF17 in chicken as a true, biological occurrence. FGF17 is also missing in the turkey, black grouse, Japanese quail and northern bobwhite genomes. These species, along with chicken, form a monophyletic clade in the order Galliformes. Four additional species, members of the clade Passeroidea, within the order Passeriformes, are also missing FGF17. Additionally, analysis of intact FGF17 in other avian lineages reveals that it is still under strong purifying selection, despite being seemingly dispensable. Thus, FGF17 likely represents a molecular spandrel arising from a genome duplication event and due to its high connectivity with FGF8/FGF18, and potential for interference with their function, is retained under strong purifying selection, despite itself not having a strong selective advantage. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Adult Drosophila melanogaster evolved for antibacterial defense invest in infection-induced expression of both humoral and cellular immunity genes

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    McGraw Elizabeth A

    2011-08-01

    Full Text Available Abstract Background While the transcription of innate immunity genes in response to bacterial infection has been well-characterised in the Drosophila model, we recently demonstrated the capacity for such transcription to evolve in flies selected for improved antibacterial defense. Here we use this experimental system to examine how insects invest in constitutive versus infection-induced transcription of immunity genes. These two strategies carry with them different consequences with respect to energetic and pleiotropic costs and may be more or less effective in improving defense depending on whether the genes contribute to humoral or cellular aspects of immunity. Findings Contrary to expectation we show that selection preferentially increased the infection-induced expression of both cellular and humoral immunity genes. Given their functional roles, infection induced increases in expression were expected for the humoral genes, while increases in constitutive expression were expected for the cellular genes. We also report a restricted ability to improve transcription of immunity genes that is on the order of 2-3 fold regardless of total transcription level of the gene. Conclusions The evolved increases in infection-induced expression of the cellular genes may result from specific cross talk with humoral pathways or from generalised strategies for enhancing immunity gene transcription. A failure to see improvements in constitutive expression of the cellular genes suggests either that increases might come at too great a cost or that patterns of expression in adults are decoupled from the larval phase where increases would be most effective. The similarity in fold change increase across all immunity genes may suggest a shared mechanism for the evolution of increased transcription in small, discrete units such as duplication of cis-regulatory elements.

  4. An NF-κB Transcription-Factor-Dependent Lineage-Specific Transcriptional Program Promotes Regulatory T Cell Identity and Function.

    Science.gov (United States)

    Oh, Hyunju; Grinberg-Bleyer, Yenkel; Liao, Will; Maloney, Dillon; Wang, Pingzhang; Wu, Zikai; Wang, Jiguang; Bhatt, Dev M; Heise, Nicole; Schmid, Roland M; Hayden, Matthew S; Klein, Ulf; Rabadan, Raul; Ghosh, Sankar

    2017-09-19

    Both conventional T (Tconv) cells and regulatory T (Treg) cells are activated through ligation of the T cell receptor (TCR) complex, leading to the induction of the transcription factor NF-κB. In Tconv cells, NF-κB regulates expression of genes essential for T cell activation, proliferation, and function. However the role of NF-κB in Treg function remains unclear. We conditionally deleted canonical NF-κB members p65 and c-Rel in developing and mature Treg cells and found they have unique but partially redundant roles. c-Rel was critical for thymic Treg development while p65 was essential for mature Treg identity and maintenance of immune tolerance. Transcriptome and NF-κB p65 binding analyses demonstrated a lineage specific, NF-κB-dependent transcriptional program, enabled by enhanced chromatin accessibility. These dual roles of canonical NF-κB in Tconv and Treg cells highlight the functional plasticity of the NF-κB signaling pathway and underscores the need for more selective strategies to therapeutically target NF-κB. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Spatio-temporal re-organization of replication foci accompanies replication domain consolidation during human pluripotent stem cell lineage specification

    Science.gov (United States)

    Wilson, Korey A.; Elefanty, Andrew G.; Stanley, Edouard G.; Gilbert, David M.

    2016-01-01

    ABSTRACT Lineage specification of both mouse and human pluripotent stem cells (PSCs) is accompanied by spatial consolidation of chromosome domains and temporal consolidation of their replication timing. Replication timing and chromatin organization are both established during G1 phase at the timing decision point (TDP). Here, we have developed live cell imaging tools to track spatio-temporal replication domain consolidation during differentiation. First, we demonstrate that the fluorescence ubiquitination cell cycle indicator (Fucci) system is incapable of demarcating G1/S or G2/M cell cycle transitions. Instead, we employ a combination of fluorescent PCNA to monitor S phase progression, cytokinesis to demarcate mitosis, and fluorescent nucleotides to label early and late replication foci and track their 3D organization into sub-nuclear chromatin compartments throughout all cell cycle transitions. We find that, as human PSCs differentiate, the length of S phase devoted to replication of spatially clustered replication foci increases, coincident with global compartmentalization of domains into temporally clustered blocks of chromatin. Importantly, re-localization and anchorage of domains was completed prior to the onset of S phase, even in the context of an abbreviated PSC G1 phase. This approach can also be employed to investigate cell fate transitions in single PSCs, which could be seen to differentiate preferentially from G1 phase. Together, our results establish real-time, live-cell imaging methods for tracking cell cycle transitions during human PSC differentiation that can be applied to study chromosome domain consolidation and other aspects of lineage specification. PMID:27433885

  6. Horizontal gene transfer: essentiality and evolvability in prokaryotes, and roles in evolutionary transitions [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Eugene V. Koonin

    2016-07-01

    Full Text Available The wide spread of gene exchange and loss in the prokaryotic world has prompted the concept of ‘lateral genomics’ to the point of an outright denial of the relevance of phylogenetic trees for evolution. However, the pronounced coherence congruence of the topologies of numerous gene trees, particularly those for (nearly universal genes, translates into the notion of a statistical tree of life (STOL, which reflects a central trend of vertical evolution. The STOL can be employed as a framework for reconstruction of the evolutionary processes in the prokaryotic world. Quantitatively, however, horizontal gene transfer (HGT dominates microbial evolution, with the rate of gene gain and loss being comparable to the rate of point mutations and much greater than the duplication rate. Theoretical models of evolution suggest that HGT is essential for the survival of microbial populations that otherwise deteriorate due to the Muller’s ratchet effect. Apparently, at least some bacteria and archaea evolved dedicated vehicles for gene transfer that evolved from selfish elements such as plasmids and viruses. Recent phylogenomic analyses suggest that episodes of massive HGT were pivotal for the emergence of major groups of organisms such as multiple archaeal phyla as well as eukaryotes. Similar analyses appear to indicate that, in addition to donating hundreds of genes to the emerging eukaryotic lineage, mitochondrial endosymbiosis severely curtailed HGT. These results shed new light on the routes of evolutionary transitions, but caution is due given the inherent uncertainty of deep phylogenies.

  7. How do obligate parasites evolve? A multi-gene phylogenetic analysis of downy mildews.

    Science.gov (United States)

    Göker, Markus; Voglmayr, Hermann; Riethmüller, Alexandra; Oberwinkler, Franz

    2007-02-01

    Plant parasitism has independently evolved as a nutrition strategy in both true fungi and Oomycetes (stramenopiles). A large number of species within phytopathogenic Oomycetes, the so-called downy mildews, are defined as obligate biotrophs since they have not, to date, been cultured on any artificial medium. Other genera like Phytophthora and Pythium can in general be cultured on standard or non-standard agar media. Within all three groups there are many important plant pathogens responsible for severe economic losses as well as damage to natural ecosystems. Although they are important model systems to elucidate the evolution of obligate parasites, the phylogenetic relationships between these genera have not been clearly resolved. Based on the most comprehensive sampling of downy mildew genera to date and a representative sample of Phytophthora subgroups, we inferred the phylogenetic relationships from a multi-gene dataset containing both coding and non-coding nuclear and mitochondrial loci. Phylogenetic analyses were conducted under several optimality criteria and the results were largely consistent between all the methods applied. Strong support is achieved for monophyly of a clade comprising both the genus Phytophthora and the obligate biotrophic species. The facultatively parasitic genus Phytophthora is shown to be at least partly paraphyletic. Monophyly of a cluster nested within Phytophthora containing all obligate parasites is strongly supported. Within the obligate biotrophic downy mildews, four morphologically or ecologically well-defined subgroups receive statistical support: (1) A cluster containing all species with brownish-violet conidiosporangia, i.e., the genera Peronospora and Pseudoperonospora; (2) a clade comprising the genera with vesicular to pyriform haustoria (Basidiophora, Benua, Bremia, Paraperonospora, Plasmopara, Plasmoverna, Protobremia); (3) a group containing species included in Hyaloperonospora and Perofascia which almost exclusively

  8. Evolution of hydra, a recently evolved testis-expressed gene with nine alternative first exons in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Shou-Tao Chen

    2007-07-01

    Full Text Available We describe here the Drosophila gene hydra that appears to have originated de novo in the melanogaster subgroup and subsequently evolved in both structure and expression level in Drosophila melanogaster and its sibling species. D. melanogaster hydra encodes a predicted protein of approximately 300 amino acids with no apparent similarity to any previously known proteins. The syntenic region flanking hydra on both sides is found in both D. ananassae and D. pseudoobscura, but hydra is found only in melanogaster subgroup species, suggesting that it originated less than approximately 13 million y ago. Exon 1 of hydra has undergone recurrent duplications, leading to the formation of nine tandem alternative exon 1s in D. melanogaster. Seven of these alternative exons are flanked on their 3' side by the transposon DINE-1 (Drosophila interspersed element-1. We demonstrate that at least four of the nine duplicated exon 1s can function as alternative transcription start sites. The entire hydra locus has also duplicated in D. simulans and D. sechellia. D. melanogaster hydra is expressed most intensely in the proximal testis, suggesting a role in late-stage spermatogenesis. The coding region of hydra has a relatively high Ka/Ks ratio between species, but the ratio is less than 1 in all comparisons, suggesting that hydra is subject to functional constraint. Analysis of sequence polymorphism and divergence of hydra shows that it has evolved under positive selection in the lineage leading to D. melanogaster. The dramatic structural changes surrounding the first exons do not affect the tissue specificity of gene expression: hydra is expressed predominantly in the testes in D. melanogaster, D. simulans, and D. yakuba. However, we have found that expression level changed dramatically (approximately >20-fold between D. melanogaster and D. simulans. While hydra initially evolved in the absence of nearby transposable element insertions, we suggest that the subsequent

  9. Development of Kras mutant lung adenocarcinoma in mice with knockout of the airway lineage-specific gene Gprc5a.

    Science.gov (United States)

    Fujimoto, Junya; Nunomura-Nakamura, Sayuri; Liu, Yihua; Lang, Wenhua; McDowell, Tina; Jakubek, Yasminka; Ezzeddine, Dalia; Kapere Ochieng, Joshua; Petersen, Jason; Davies, Gareth; Fukuoka, Junya; Wistuba, Ignacio I; Ehli, Erik; Fowler, Jerry; Scheet, Paul; Kadara, Humam

    2017-10-15

    Despite the urgency for prevention and treatment of lung adenocarcinoma (LUAD), we still do not know drivers in pathogenesis of the disease. Earlier work revealed that mice with knockout of the G-protein coupled receptor Gprc5a develop late onset lung tumors including LUADs. Here, we sought to further probe the impact of Gprc5a expression on LUAD pathogenesis. We first surveyed GPRC5A expression in human tissues and found that GPRC5A was markedly elevated in human normal lung relative to other normal tissues and was consistently downregulated in LUADs. In sharp contrast to wild-type littermates, Gprc5a(-/-) mice treated chronically with the nicotine-specific carcinogen NNK developed LUADs by 6 months following NNK exposure. Immunofluorescence analysis revealed that the LUADs exhibited abundant expression of surfactant protein C and lacked the clara cell marker Ccsp, suggesting that these LUADs originated from alveolar type II cells. Next, we sought to survey genome-wide alterations in the pathogenesis of Gprc5a(-/-) LUADs. Using whole exome sequencing, we found that carcinogen-induced LUADs exhibited markedly higher somatic mutation burdens relative to spontaneous tumors. All LUADs were found to harbor somatic mutations in the Kras oncogene (p. G12D or p. Q61R). In contrast to spontaneous lesions, carcinogen-induced Gprc5a(-/-) LUADs exhibited mutations (variants and copy number gains) in additional drivers (Atm, Kmt2d, Nf1, Trp53, Met, Ezh2). Our study underscores genomic alterations that represent early events in the development of Kras mutant LUAD following Gprc5a loss and tobacco carcinogen exposure and that may constitute targets for prevention and early treatment of this disease. © 2017 UICC.

  10. Lineage-specific group II intron gains and losses of the mitochondrial rps3 gene in gymnosperms.

    Science.gov (United States)

    Regina, Teresa M R; Quagliariello, Carla

    2010-08-01

    According to PCR assays and sequencing, we now report the shared presence of two rps3 introns, namely the rps3i74 and the rps3i249, in the mitochondria of all the classes representing the surviving lineages of gymnosperms, and unveil several lineages experiencing intron loss. Interestingly, the rps3 intron gains and losses within the four groups of gymnosperms let us sort out the Pinaceae and the non-Pinaceae into intron (+)- and intron (-)-lineages, respectively. Worthy of mention is also the finding that only Gnetum within the Gnetales harbours both the rps3 introns. This intron distribution pattern is consistent with the hypothesis that the two rps3 introns were likely present in the common ancestor of the seed plants and, then, independently lost in the non-Pinaceae during gymnosperm evolution. The derived secondary structural model of the novel group IIA intron improves our understanding of the significance and origin of the extraordinary length polymorphisms observed among rps3i249 orthologs. Despite the remarkable structural plasticity to adopt and reject introns, the rps3 mRNAs undergo accurate processing by splicing and extensive editing in gymnosperm mitochondria. This study provides additional insights into the evolutionarily high dynamics of mitochondrial introns which may come and go in closely related plant species. The turnover of the mitochondrial rps3 group II introns seen among lineages of seed plants further suggests that these introns might be an additional signature to discriminate between particularly cryptical taxonomic groups for which there is a need of a further evaluation of their evolutionary affiliation. Copyright 2010 Elsevier Masson SAS. All rights reserved.

  11. Cyclic incrementality in competitive coevolution: Evolvability through pseudo-Baldwinian switching-genes

    NARCIS (Netherlands)

    Janssen, R.; Nolfi, S.; Haselager, W.F.G.; Sprinkhuizen-Kuyper, I.G.

    2016-01-01

    Coevolving systems are notoriously difficult to understand. This is largely due to the Red Queen effect that dictates heterospecific fitness interdependence. In simulation studies of coevolving systems, master tournaments are often used to obtain more informed fitness measures by testing evolved

  12. Cyanobacterial symbionts diverged in the late Cretaceous towards lineage-specific nitrogen fixation factories in single-celled phytoplankton.

    Science.gov (United States)

    Cornejo-Castillo, Francisco M; Cabello, Ana M; Salazar, Guillem; Sánchez-Baracaldo, Patricia; Lima-Mendez, Gipsi; Hingamp, Pascal; Alberti, Adriana; Sunagawa, Shinichi; Bork, Peer; de Vargas, Colomban; Raes, Jeroen; Bowler, Chris; Wincker, Patrick; Zehr, Jonathan P; Gasol, Josep M; Massana, Ramon; Acinas, Silvia G

    2016-03-22

    The unicellular cyanobacterium UCYN-A, one of the major contributors to nitrogen fixation in the open ocean, lives in symbiosis with single-celled phytoplankton. UCYN-A includes several closely related lineages whose partner fidelity, genome-wide expression and time of evolutionary divergence remain to be resolved. Here we detect and distinguish UCYN-A1 and UCYN-A2 lineages in symbiosis with two distinct prymnesiophyte partners in the South Atlantic Ocean. Both symbiotic systems are lineage specific and differ in the number of UCYN-A cells involved. Our analyses infer a streamlined genome expression towards nitrogen fixation in both UCYN-A lineages. Comparative genomics reveal a strong purifying selection in UCYN-A1 and UCYN-A2 with a diversification process ∼91 Myr ago, in the late Cretaceous, after the low-nutrient regime period occurred during the Jurassic. These findings suggest that UCYN-A diversified in a co-evolutionary process, wherein their prymnesiophyte partners acted as a barrier driving an allopatric speciation of extant UCYN-A lineages.

  13. Cheetahs have 4 serum amyloid a genes evolved through repeated duplication events.

    Science.gov (United States)

    Chen, Lei; Une, Yumi; Higuchi, Keiichi; Mori, Masayuki

    2012-01-01

    Amyloid A (AA) amyloidosis is a leading cause of mortality in captive cheetahs (Acinonyx jubatus). We performed genome walking and PCR cloning and revealed that cheetahs have 4 SAA genes (provisionally named SAA1A, SAA1B, SAA3A, and SAA3B). In addition, we identified multiple nucleotide polymorphisms in the 4 SAA genes by screening 51 cheetahs. The polymorphisms defined 4, 7, 6, and 4 alleles for SAA1A, SAA3A, SAA1B, and SAA3B, respectively. Pedigree analysis of the inheritance of genotypes for the SAA genes revealed that specific combinations of alleles for the 4 SAA genes cosegregated as a unit (haplotype) in pedigrees, indicating that the 4 genes were linked on the same chromosome. Notably, cheetah SAA1A and SAA1B were highly homologous in their nucleotide sequences. Likewise, SAA3A and SAA3B genes were homologous. These observations suggested a model for the evolution of the 4 SAA genes in cheetahs in which duplication of an ancestral SAA gene first gave rise to SAA1 and SAA3. Subsequently, each gene duplicated one more time, uniquely making 4 genes in the cheetah genome. The monomorphism of the cheetah SAA1A protein might be one of the factors responsible for the high incidence of AA amyloidosis in this species.

  14. Rapidly evolving genes in pathogens: methods for detecting positive selection and examples among fungi, bacteria, viruses and protists.

    Science.gov (United States)

    Aguileta, Gabriela; Refrégier, Guislaine; Yockteng, Roxana; Fournier, Elisabeth; Giraud, Tatiana

    2009-07-01

    The ongoing coevolutionary struggle between hosts and pathogens, with hosts evolving to escape pathogen infection and pathogens evolving to escape host defences, can generate an 'arms race', i.e., the occurrence of recurrent selective sweeps that each favours a novel resistance or virulence allele that goes to fixation. Host-pathogen coevolution can alternatively lead to a 'trench warfare', i.e., balancing selection, maintaining certain alleles at loci involved in host-pathogen recognition over long time scales. Recently, technological and methodological progress has enabled detection of footprints of selection directly on genes, which can provide useful insights into the processes of coevolution. This knowledge can also have practical applications, for instance development of vaccines or drugs. Here we review the methods for detecting genes under positive selection using divergence data (i.e., the ratio of nonsynonymous to synonymous substitution rates, d(N)/d(S)). We also review methods for detecting selection using polymorphisms, such as methods based on F(ST) measures, frequency spectrum, linkage disequilibrium and haplotype structure. In the second part, we review examples where targets of selection have been identified in pathogens using these tests. Genes under positive selection in pathogens have mostly been sought among viruses, bacteria and protists, because of their paramount importance for human health. Another focus is on fungal pathogens owing to their agronomic importance. We finally discuss promising directions in pathogen studies, such as detecting selection in non-coding regions.

  15. Rapidly evolving marmoset MSMB genes are differently expressed in the male genital tract

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    Ceder Yvonne

    2009-09-01

    Full Text Available Abstract Background Beta-microseminoprotein, an abundant component in prostatic fluid, is encoded by the potential tumor suppressor gene MSMB. Some New World monkeys carry several copies of this gene, in contrast to most mammals, including humans, which have one only. Here we have investigated the background for the species difference by analyzing the chromosomal organization and expression of MSMB in the common marmoset (Callithrix jacchus. Methods Genes were identified in the Callithrix jacchus genome database using bioinformatics and transcripts were analyzed by RT-PCR and quantified by real time PCR in the presence of SYBR green. Results The common marmoset has five MSMB: one processed pseudogene and four functional genes. The latter encompass homologous genomic regions of 32-35 kb, containing the genes of 12-14 kb and conserved upstream and downstream regions of 14-19 kb and 3-4 kb. One gene, MSMB1, occupies the same position on the chromosome as the single human gene. On the same chromosome, but several Mb away, is another MSMB locus situated with MSMB2, MSMB3 and MSMB4 arranged in tandem. Measurements of transcripts demonstrated that all functional genes are expressed in the male genital tract, generating very high transcript levels in the prostate. The transcript levels in seminal vesicles and testis are two and four orders of magnitude lower. A single gene, MSMB3, accounts for more than 90% of MSMB transcripts in both the prostate and the seminal vesicles, whereas in the testis around half of the transcripts originate from MSMB2. These genes display rapid evolution with a skewed distribution of mutated nucleotides; in MSMB2 they affect nucleotides encoding the N-terminal Greek key domain, whereas in MSMB3 it is the C-terminal MSMB-unique domain that is affected. Conclusion Callitrichide monkeys have four functional MSMB that are all expressed in the male genital tract, but the product from one gene, MSMB3, will predominate in seminal

  16. Evaluation of customised lineage-specific sets of MIRU-VNTR loci for genotyping Mycobacterium tuberculosis complex isolates in Ghana.

    Science.gov (United States)

    Asante-Poku, Adwoa; Nyaho, Michael Selasi; Borrell, Sonia; Comas, Iñaki; Gagneux, Sebastien; Yeboah-Manu, Dorothy

    2014-01-01

    Different combinations of variable number of tandem repeat (VNTR) loci have been proposed for genotyping Mycobacterium tuberculosis complex (MTBC). Existing VNTR schemes show different discriminatory capacity among the six human MTBC lineages. Here, we evaluated the discriminatory power of a "customized MIRU12" loci format proposed previously by Comas et al. based on the standard 24 loci defined by Supply et al. for VNTR-typing of MTBC in Ghana. One hundred and fifty-eight MTBC isolates classified into Lineage 4 and Lineage 5 were used to compare a customized lineage-specific panel of 12 MIRU-VNTR loci ("customized MIRU-12") to the standard MIRU-15 genotyping scheme. The resolution power of each typing method was determined based on the Hunter-Gaston- Discriminatory Index (HGDI). A minimal set of customized MIRU-VNTR loci for typing Lineages 4 (Euro-American) and 5 (M. africanum West African 1) strains from Ghana was defined based on the cumulative HGDI. Among the 106 Lineage 4 strains, the customized MIRU-12 identified a total of 104 distinct genotypes consisting of 2 clusters of 2 isolates each (clustering rate 1.8%), and 102 unique strains while standard MIRU-15 yielded a total of 105 different genotypes, including 1 cluster of 2 isolates (clustering rate: 0.9%) and 104 singletons. Among, 52 Lineage 5 isolates, customized MIRU-12 genotyping defined 51 patterns with 1 cluster of 2 isolates (clustering rate: 0.9%) and 50 unique strains whereas MIRU-15 classified all 52 strains as unique. Cumulative HGDI values for customized MIRU-12 for Lineages 4 and 5 were 0.98 respectively whilst that of standard MIRU-15 was 0.99. A union of loci from the customised MIRU-12 and standard MIRU-15 revealed a set of customized eight highly discriminatory loci: 4052, 2163B, 40, 4165, 2165, 10,16 and 26 with a cumulative HGDI of 0.99 for genotyping Lineage 4 and 5 strains from Ghana.

  17. The Earliest Transcribed Zygotic Genes Are Short, Newly Evolved, and Different across Species

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    Patricia Heyn

    2014-01-01

    Full Text Available The transition from maternal to zygotic control is fundamental to the life cycle of all multicellular organisms. It is widely believed that genomes are transcriptionally inactive from fertilization until zygotic genome activation (ZGA. Thus, the earliest genes expressed probably support the rapid cell divisions that precede morphogenesis and, if so, might be evolutionarily conserved. Here, we identify the earliest zygotic transcripts in the zebrafish, Danio rerio, through metabolic labeling and purification of RNA from staged embryos. Surprisingly, the mitochondrial genome was highly active from the one-cell stage onwards, showing that significant transcriptional activity exists at fertilization. We show that 592 nuclear genes become active when cell cycles are still only 15 min long, confining expression to relatively short genes. Furthermore, these zygotic genes are evolutionarily younger than those expressed at other developmental stages. Comparison of fish, fly, and mouse data revealed different sets of genes expressed at ZGA. This species specificity uncovers an evolutionary plasticity in early embryogenesis that probably confers substantial adaptive potential.

  18. Low rates of lateral gene transfer among metabolic genes define the evolving biogeochemical niches of archaea through deep time.

    Science.gov (United States)

    Blank, Carrine E

    2012-01-01

    Phylogenomic analyses of archaeal genome sequences are providing windows into the group's evolutionary past, even though most archaeal taxa lack a conventional fossil record. Here, phylogenetic analyses were performed using key metabolic genes that define the metabolic niche of microorganisms. Such genes are generally considered to have undergone high rates of lateral gene transfer. Many gene sequences formed clades that were identical, or similar, to the tree constructed using large numbers of genes from the stable core of the genome. Surprisingly, such lateral transfer events were readily identified and quantifiable, occurring only a relatively small number of times in the archaeal domain of life. By placing gene acquisition events into a temporal framework, the rates by which new metabolic genes were acquired can be quantified. The highest lateral transfer rates were among cytochrome oxidase genes that use oxygen as a terminal electron acceptor (with a total of 12-14 lateral transfer events, or 3.4-4.0 events per billion years, across the entire archaeal domain). Genes involved in sulfur or nitrogen metabolism had much lower rates, on the order of one lateral transfer event per billion years. This suggests that lateral transfer rates of key metabolic proteins are rare and not rampant.

  19. Fructan Biosynthetic and Breakdown Enzymes in Dicots Evolved From Different Invertases. Expression of Fructan Genes Throughout Chicory Development

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    Wim Van den Ende

    2002-01-01

    Full Text Available Fructans are fructose-based oligo- and polymers that serve as reserve carbohydrates in many plant species. The biochemistry of fructan biosynthesis in dicots has been resolved, and the respective cDNAs have been cloned. Recent progress has now succeeded in elucidating the biochemistry and molecular biology of fructan biodegradation in chicory, an economically important species used for commercial inulin extraction. Unlike fructan biosynthetic genes that originated from vacuolar-type invertase, fructan exohydrolases (FEHs seem to have evolved from a cell-wall invertase ancestor gene that later obtained a low iso-electric point and a vacuolar targeting signal. Expression analysis reveals that fructan enzymes are controlled mainly at the transcriptional level. Using chicory as a model system, northern analysis was consistent with enzymatic activity measurements and observed carbohydrate changes throughout its development.

  20. Evolving lessons on nanomaterial-coated viral vectors for local and systemic gene therapy.

    Science.gov (United States)

    Kasala, Dayananda; Yoon, A-Rum; Hong, Jinwoo; Kim, Sung Wan; Yun, Chae-Ok

    2016-07-01

    Viral vectors are promising gene carriers for cancer therapy. However, virus-mediated gene therapies have demonstrated insufficient therapeutic efficacy in clinical trials due to rapid dissemination to nontarget tissues and to the immunogenicity of viral vectors, resulting in poor retention at the disease locus and induction of adverse inflammatory responses in patients. Further, the limited tropism of viral vectors prevents efficient gene delivery to target tissues. In this regard, modification of the viral surface with nanomaterials is a promising strategy to augment vector accumulation at the target tissue, circumvent the host immune response, and avoid nonspecific interactions with the reticuloendothelial system or serum complement. In the present review, we discuss various chemical modification strategies to enhance the therapeutic efficacy of viral vectors delivered either locally or systemically. We conclude by highlighting the salient features of various nanomaterial-coated viral vectors and their prospects and directions for future research.

  1. Bacterial and fungal chitinase chiJ orthologs evolve under different selective constraints following horizontal gene transfer

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    Ubhayasekera Wimal

    2012-10-01

    Full Text Available Abstract Background Certain bacteria from the genus Streptomyces are currently used as biological control agents against plant pathogenic fungi. Hydrolytic enzymes that degrade fungal cell wall components, such as chitinases, are suggested as one possible mechanism in biocontrol interactions. Adaptive evolution of chitinases are previously reported for plant chitinases involved in defence against fungal pathogens, and in fungal chitinases involved in fungal-fungal interactions. In this study we investigated the molecular evolution of chitinase chiJ in the bacterial genus Streptomyces. In addition, as chiJ orthologs are previously reported in certain fungal species as a result from horizontal gene transfer, we conducted a comparative study of differences in evolutionary patterns between bacterial and fungal taxa. Findings ChiJ contained three sites evolving under strong positive selection and four groups of co-evolving sites. Regions of high amino acid diversity were predicted to be surface-exposed and associated with coil regions that connect certain α-helices and β-strands in the family 18 chitinase TIM barrel structure, but not associated with the catalytic cleft. The comparative study with fungal ChiJ orthologs identified three regions that display signs of type 1 functional divergence, where unique adaptations in the bacterial and fungal taxa are driven by positive selection. Conclusions The identified surface-exposed regions of chitinase ChiJ where sequence diversification is driven by positive selection may putatively be related to functional divergence between bacterial and fungal orthologs. These results show that ChiJ orthologs have evolved under different selective constraints following the horizontal gene transfer event.

  2. An RNA gene expressed during cortical development evolved rapidly in humans

    DEFF Research Database (Denmark)

    Pollard, Katherine S; Salama, Sofie R; Lambert, Nelle

    2006-01-01

    of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these 'human accelerated regions', HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal-Retzius neurons...

  3. Lineage-specific positive selection at the merozoite surface protein 1 (msp1 locus of Plasmodium vivax and related simian malaria parasites

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    Kawai Satoru

    2010-02-01

    -specifically on msp1. Conclusions The present results indicate that the msp1 locus of P. vivax and related parasite species has lineage-specific unique evolutionary history with positive selection. P. vivax and related simian malaria parasites offer an interesting system toward understanding host species-dependent adaptive evolution of immune-target surface antigen genes such as msp1.

  4. Evaluation of customised lineage-specific sets of MIRU-VNTR loci for genotyping Mycobacterium tuberculosis complex isolates in Ghana.

    Directory of Open Access Journals (Sweden)

    Adwoa Asante-Poku

    Full Text Available BACKGROUND: Different combinations of variable number of tandem repeat (VNTR loci have been proposed for genotyping Mycobacterium tuberculosis complex (MTBC. Existing VNTR schemes show different discriminatory capacity among the six human MTBC lineages. Here, we evaluated the discriminatory power of a "customized MIRU12" loci format proposed previously by Comas et al. based on the standard 24 loci defined by Supply et al. for VNTR-typing of MTBC in Ghana. METHOD: One hundred and fifty-eight MTBC isolates classified into Lineage 4 and Lineage 5 were used to compare a customized lineage-specific panel of 12 MIRU-VNTR loci ("customized MIRU-12" to the standard MIRU-15 genotyping scheme. The resolution power of each typing method was determined based on the Hunter-Gaston- Discriminatory Index (HGDI. A minimal set of customized MIRU-VNTR loci for typing Lineages 4 (Euro-American and 5 (M. africanum West African 1 strains from Ghana was defined based on the cumulative HGDI. RESULTS AND CONCLUSION: Among the 106 Lineage 4 strains, the customized MIRU-12 identified a total of 104 distinct genotypes consisting of 2 clusters of 2 isolates each (clustering rate 1.8%, and 102 unique strains while standard MIRU-15 yielded a total of 105 different genotypes, including 1 cluster of 2 isolates (clustering rate: 0.9% and 104 singletons. Among, 52 Lineage 5 isolates, customized MIRU-12 genotyping defined 51 patterns with 1 cluster of 2 isolates (clustering rate: 0.9% and 50 unique strains whereas MIRU-15 classified all 52 strains as unique. Cumulative HGDI values for customized MIRU-12 for Lineages 4 and 5 were 0.98 respectively whilst that of standard MIRU-15 was 0.99. A union of loci from the customised MIRU-12 and standard MIRU-15 revealed a set of customized eight highly discriminatory loci: 4052, 2163B, 40, 4165, 2165, 10,16 and 26 with a cumulative HGDI of 0.99 for genotyping Lineage 4 and 5 strains from Ghana.

  5. A complete mitochondrial genome of wheat (Triticum aestivum cv. Chinese Yumai), and fast evolving mitochondrial genes in higher plants.

    Science.gov (United States)

    Cui, Peng; Liu, Huitao; Lin, Qiang; Ding, Feng; Zhuo, Guoyin; Hu, Songnian; Liu, Dongcheng; Yang, Wenlong; Zhan, Kehui; Zhang, Aimin; Yu, Jun

    2009-12-01

    Plant mitochondrial genomes, encoding necessary proteins involved in the system of energy production, play an important role in the development and reproduction of the plant. They occupy a specific evolutionary pattern relative to their nuclear counterparts. Here, we determined the winter wheat (Triticum aestivum cv. Chinese Yumai) mitochondrial genome in a length of 452 and 526 bp by shotgun sequencing its BAC library. It contains 202 genes, including 35 known protein-coding genes, three rRNA and 17 tRNA genes, as well as 149 open reading frames (ORFs; greater than 300 bp in length). The sequence is almost identical to the previously reported sequence of the spring wheat (T. aestivum cv. Chinese Spring); we only identified seven SNPs (three transitions and four transversions) and 10 indels (insertions and deletions) between the two independently acquired sequences, and all variations were found in non-coding regions. This result confirmed the accuracy of the previously reported mitochondrial sequence of the Chinese Spring wheat. The nucleotide frequency and codon usage of wheat are common among the lineage of higher plant with a high AT-content of 58%. Molecular evolutionary analysis demonstrated that plant mitochondrial genomes evolved at different rates, which may correlate with substantial variations in metabolic rate and generation time among plant lineages. In addition, through the estimation of the ratio of non-synonymous to synonymous substitution rates between orthologous mitochondrion-encoded genes of higher plants, we found an accelerated evolutionary rate that seems to be the result of relaxed selection.

  6. Superparamagnetic Nanoparticles and RNAi-Mediated Gene Silencing: Evolving Class of Cancer Diagnostics and Therapeutics

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    Sanchareeka Dey

    2012-01-01

    Full Text Available The ever increasing death of patients affected by various types of fatal cancers is of concern worldwide. Curative attempts by radiation/chemotherapy and surgery are often a failure in the long run. Moreover, adverse side effects of such treatments burden the patients with painful survival at the last phase of their life. The failure of early diagnosis is one of the root causes of the problem. Intensive research activities are being pursued in reputed laboratories across the globe to find superior diagnostics and therapeutics. Over the last decade, a number of publications have highlighted RNA interference based silencing of cancer-related gene expression as a promising technology to tackle the aforesaid problems. Superparamagnetic iron oxide nanoparticles (SPIONs are reported to be excellent vehicles for short-interfering RNA (siRNA. The SPION-siRNA conjugate is biocompatible, stable, and amenable to specific targeting and can cross the blood brain barrier. The issues related to their synthesis, surface properties, delivery, tracking, imaging in relevance to cancer diagnostic and therapeutic, and so forth demand an extensive review, and we have addressed these aspects in this paper. The future prospects of the technology have also been traced.

  7. Maintaining evolvability.

    Science.gov (United States)

    Crow, James F

    2008-12-01

    Although molecular methods, such as QTL mapping, have revealed a number of loci with large effects, it is still likely that the bulk of quantitative variability is due to multiple factors, each with small effect. Typically, these have a large additive component. Conventional wisdom argues that selection, natural or artificial, uses up additive variance and thus depletes its supply. Over time, the variance should be reduced, and at equilibrium be near zero. This is especially expected for fitness and traits highly correlated with it. Yet, populations typically have a great deal of additive variance, and do not seem to run out of genetic variability even after many generations of directional selection. Long-term selection experiments show that populations continue to retain seemingly undiminished additive variance despite large changes in the mean value. I propose that there are several reasons for this. (i) The environment is continually changing so that what was formerly most fit no longer is. (ii) There is an input of genetic variance from mutation, and sometimes from migration. (iii) As intermediate-frequency alleles increase in frequency towards one, producing less variance (as p --> 1, p(1 - p) --> 0), others that were originally near zero become more common and increase the variance. Thus, a roughly constant variance is maintained. (iv) There is always selection for fitness and for characters closely related to it. To the extent that the trait is heritable, later generations inherit a disproportionate number of genes acting additively on the trait, thus increasing genetic variance. For these reasons a selected population retains its ability to evolve. Of course, genes with large effect are also important. Conspicuous examples are the small number of loci that changed teosinte to maize, and major phylogenetic changes in the animal kingdom. The relative importance of these along with duplications, chromosome rearrangements, horizontal transmission and polyploidy

  8. Rapidly Evolving Genes Are Key Players in Host Specialization and Virulence of the Fungal Wheat Pathogen Zymoseptoria tritici (Mycosphaerella graminicola.

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    Stephan Poppe

    2015-07-01

    Full Text Available The speciation of pathogens can be driven by divergent host specialization. Specialization to a new host is possible via the acquisition of advantageous mutations fixed by positive selection. Comparative genome analyses of closely related species allows for the identification of such key substitutions via inference of genome-wide signatures of positive selection. We previously used a comparative genomics framework to identify genes that have evolved under positive selection during speciation of the prominent wheat pathogen Zymoseptoria tritici (synonym Mycosphaerella graminicola. In this study, we conducted functional analyses of four genes exhibiting strong signatures of positive selection in Z. tritici. We deleted the four genes in Z. tritici and confirm a virulence-related role of three of the four genes ΔZt80707, ΔZt89160 and ΔZt103264. The two mutants ΔZt80707 and ΔZt103264 show a significant reduction in virulence during infection of wheat; the ΔZt89160 mutant causes a hypervirulent phenotype in wheat. Mutant phenotypes of ΔZt80707, ΔZt89160 and ΔZt103264 can be restored by insertion of the wild-type genes. However, the insertion of the Zt80707 and Zt89160 orthologs from Z. pseudotritici and Z. ardabiliae do not restore wild-type levels of virulence, suggesting that positively selected substitutions in Z. tritici may relate to divergent host specialization. Interestingly, the gene Zt80707 encodes also a secretion signal that targets the protein for cell secretion. This secretion signal is however only transcribed in Z. tritici, suggesting that Z. tritici-specific substitutions relate to a new function of the protein in the extracellular space of the wheat-Z. tritici interaction. Together, the results presented here highlight that Zt80707, Zt103264 and Zt89160 represent key genes involved in virulence and host-specific disease development of Z. tritici. Our findings illustrate that evolutionary predictions provide a powerful tool

  9. Congenic strain analysis reveals genes that are rapidly evolving components of a prezygotic isolation mechanism mediating incipient reinforcement.

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    Christina M Laukaitis

    Full Text Available Two decades ago, we developed a congenic strain of Mus musculus, called b-congenic, by replacing the androgen-binding protein Abpa27(a allele in the C3H/HeJ genome with the Abpa27(b allele from DBA/2J. We and other researchers used this b-congenic strain and its C3H counterpart, the a-congenic strain, to test the hypothesis that, given the choice between signals from two strains with different a27 alleles on the same genetic background, test subjects would prefer the homosubspecific one. It was our purpose in undertaking this study to characterize the segment transferred from DBA to the C3H background in producing the b-congenic strain on which a role for ABPA27 in behavior has been predicated. We determined the size of the chromosome 7 segment transferred from DBA and the genes it contains that might influence preference. We found that the "functional" DBA segment is about 1% the size of the mouse haploid genome and contains at least 29 genes expressed in salivary glands, however, only three of these encode proteins identified in the mouse salivary proteome. At least two of the three genes Abpa27, Abpbg26 and Abpbg27 encoding the subunits of androgen-binding protein ABP dimers evolved under positive selection and the third one may have also. In the sense that they are subunits of the same two functional entities, the ABP dimers, we propose that their evolutionary histories might not be independent of each other.

  10. Evolutionary origins of Brassicaceae specific genes in Arabidopsis thaliana

    Science.gov (United States)

    2011-01-01

    Background All sequenced genomes contain a proportion of lineage-specific genes, which exhibit no sequence similarity to any genes outside the lineage. Despite their prevalence, the origins and functions of most lineage-specific genes remain largely unknown. As more genomes are sequenced opportunities for understanding evolutionary origins and functions of lineage-specific genes are increasing. Results This study provides a comprehensive analysis of the origins of lineage-specific genes (LSGs) in Arabidopsis thaliana that are restricted to the Brassicaceae family. In this study, lineage-specific genes within the nuclear (1761 genes) and mitochondrial (28 genes) genomes are identified. The evolutionary origins of two thirds of the lineage-specific genes within the Arabidopsis thaliana genome are also identified. Almost a quarter of lineage-specific genes originate from non-lineage-specific paralogs, while the origins of ~10% of lineage-specific genes are partly derived from DNA exapted from transposable elements (twice the proportion observed for non-lineage-specific genes). Lineage-specific genes are also enriched in genes that have overlapping CDS, which is consistent with such novel genes arising from overprinting. Over half of the subset of the 958 lineage-specific genes found only in Arabidopsis thaliana have alignments to intergenic regions in Arabidopsis lyrata, consistent with either de novo origination or differential gene loss and retention, with both evolutionary scenarios explaining the lineage-specific status of these genes. A smaller number of lineage-specific genes with an incomplete open reading frame across different Arabidopsis thaliana accessions are further identified as accession-specific genes, most likely of recent origin in Arabidopsis thaliana. Putative de novo origination for two of the Arabidopsis thaliana-only genes is identified via additional sequencing across accessions of Arabidopsis thaliana and closely related sister species

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

    Science.gov (United States)

    Kerr, Charlotte L; Bhattacharyya, Tapan; Xavier, Samanta C C; Barros, Juliana H; Lima, Valdirene S; Jansen, Ana M; Miles, Michael A

    2016-11-15

    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. 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). 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. 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.

  12. The rhomboids: a nearly ubiquitous family of intramembrane serine proteases that probably evolved by multiple ancient horizontal gene transfers.

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    Koonin, Eugene V; Makarova, Kira S; Rogozin, Igor B; Davidovic, Laetitia; Letellier, Marie-Claude; Pellegrini, Luca

    2003-01-01

    The rhomboid family of polytopic membrane proteins shows a level of evolutionary conservation unique among membrane proteins. They are present in nearly all the sequenced genomes of archaea, bacteria and eukaryotes, with the exception of several species with small genomes. On the basis of experimental studies with the developmental regulator rhomboid from Drosophila and the AarA protein from the bacterium Providencia stuartii, the rhomboids are thought to be intramembrane serine proteases whose signaling function is conserved in eukaryotes and prokaryotes. Phylogenetic tree analysis carried out using several independent methods for tree constructions and the corresponding statistical tests suggests that, despite its broad distribution in all three superkingdoms, the rhomboid family was not present in the last universal common ancestor of extant life forms. Instead, we propose that rhomboids evolved in bacteria and have been acquired by archaea and eukaryotes through several independent horizontal gene transfers. In eukaryotes, two distinct, ancient acquisitions apparently gave rise to the two major subfamilies, typified by rhomboid and PARL (presenilins-associated rhomboid-like protein), respectively. Subsequent evolution of the rhomboid family in eukaryotes proceeded by multiple duplications and functional diversification through the addition of extra transmembrane helices and other domains in different orientations relative to the conserved core that harbors the protease activity. Although the near-universal presence of the rhomboid family in bacteria, archaea and eukaryotes appears to suggest that this protein is part of the heritage of the last universal common ancestor, phylogenetic tree analysis indicates a likely bacterial origin with subsequent dissemination by horizontal gene transfer. This emphasizes the importance of explicit phylogenetic analysis for the reconstruction of ancestral life forms. A hypothetical scenario for the origin of intracellular

  13. Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Li, Yingrui; Xu, Xun; Song, Luting

    2012-01-01

    sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading...... to two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively...

  14. Towards an understanding of lineage specification in hematopoietic stem cells: a mathematical model for the interaction of transcription factors GATA-1 and PU.1.

    Science.gov (United States)

    Roeder, Ingo; Glauche, Ingmar

    2006-08-21

    In addition to their self-renewal capabilities, hematopoietic stem cells guarantee the continuous supply of fully differentiated, functional cells of various types in the peripheral blood. The process which controls differentiation into the different lineages of the hematopoietic system (erythroid, myeloid, lymphoid) is referred to as lineage specification. It requires a potentially multi-step decision sequence which determines the fate of the cells and their successors. It is generally accepted that lineage specification is regulated by a complex system of interacting transcription factors. However, the underlying principles controlling this regulation are currently unknown. Here, we propose a simple quantitative model describing the interaction of two transcription factors. This model is motivated by experimental observations on the transcription factors GATA-1 and PU.1, both known to act as key regulators and potential antagonists in the erythroid vs. myeloid differentiation processes of hematopoietic progenitor cells. We demonstrate the ability of the model to account for the observed switching behavior of a transition from a state of low expression of both factors (undifferentiated state) to the dominance of one factor (differentiated state). Depending on the parameter choice, the model predicts two different possibilities to explain the experimentally suggested, stem cell characterizing priming state of low level co-expression. Whereas increasing transcription rates are sufficient to induce differentiation in one scenario, an additional system perturbation (by stochastic fluctuations or directed impulses) of transcription factor levels is required in the other case.

  15. Lineage-specific expansions of retroviral insertions within the genomes of African great apes but not humans and orangutans.

    Directory of Open Access Journals (Sweden)

    Chris T Yohn

    2005-04-01

    Full Text Available Retroviral infections of the germline have the potential to episodically alter gene function and genome structure during the course of evolution. Horizontal transmissions between species have been proposed, but little evidence exists for such events in the human/great ape lineage of evolution. Based on analysis of finished BAC chimpanzee genome sequence, we characterize a retroviral element (Pan troglodytes endogenous retrovirus 1 [PTERV1] that has become integrated in the germline of African great ape and Old World monkey species but is absent from humans and Asian ape genomes. We unambiguously map 287 retroviral integration sites and determine that approximately 95.8% of the insertions occur at non-orthologous regions between closely related species. Phylogenetic analysis of the endogenous retrovirus reveals that the gorilla and chimpanzee elements share a monophyletic origin with a subset of the Old World monkey retroviral elements, but that the average sequence divergence exceeds neutral expectation for a strictly nuclear inherited DNA molecule. Within the chimpanzee, there is a significant integration bias against genes, with only 14 of these insertions mapping within intronic regions. Six out of ten of these genes, for which there are expression data, show significant differences in transcript expression between human and chimpanzee. Our data are consistent with a retroviral infection that bombarded the genomes of chimpanzees and gorillas independently and concurrently, 3-4 million years ago. We speculate on the potential impact of such recent events on the evolution of humans and great apes.

  16. Cobalamin-independent methionine synthase (MetE: a face-to-face double barrel that evolved by gene duplication.

    Directory of Open Access Journals (Sweden)

    Robert Pejchal

    2005-02-01

    Full Text Available Cobalamin-independent methionine synthase (MetE catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH, both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two (betaalpha(8 barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys(3Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E.Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

  17. Cobalamin-Independent Methionine Synthase (MetE): A Face-to-Face Double Barrel that Evolved by Gene Duplication

    Energy Technology Data Exchange (ETDEWEB)

    Pejcha, Robert; Ludwig, Martha L. (Michigan)

    2010-03-08

    Cobalamin-independent methionine synthase (MetE) catalyzes the transfer of a methyl group from methyltetrahydrofolate to L-homocysteine (Hcy) without using an intermediate methyl carrier. Although MetE displays no detectable sequence homology with cobalamin-dependent methionine synthase (MetH), both enzymes require zinc for activation and binding of Hcy. Crystallographic analyses of MetE from T. maritima reveal an unusual dual-barrel structure in which the active site lies between the tops of the two ({beta}{alpha}){sub 8} barrels. The fold of the N-terminal barrel confirms that it has evolved from the C-terminal polypeptide by gene duplication; comparisons of the barrels provide an intriguing example of homologous domain evolution in which binding sites are obliterated. The C-terminal barrel incorporates the zinc ion that binds and activates Hcy. The zinc-binding site in MetE is distinguished from the (Cys){sub 3}Zn site in the related enzymes, MetH and betaine-homocysteine methyltransferase, by its position in the barrel and by the metal ligands, which are histidine, cysteine, glutamate, and cysteine in the resting form of MetE. Hcy associates at the face of the metal opposite glutamate, which moves away from the zinc in the binary E {center_dot} Hcy complex. The folate substrate is not intimately associated with the N-terminal barrel; instead, elements from both barrels contribute binding determinants in a binary complex in which the folate substrate is incorrectly oriented for methyl transfer. Atypical locations of the Hcy and folate sites in the C-terminal barrel presumably permit direct interaction of the substrates in a ternary complex. Structures of the binary substrate complexes imply that rearrangement of folate, perhaps accompanied by domain rearrangement, must occur before formation of a ternary complex that is competent for methyl transfer.

  18. The ubiquitous transcription factor CTCF promotes lineage-specific epigenomic remodeling and establishment of transcriptional networks driving cell differentiation.

    Science.gov (United States)

    Dubois-Chevalier, Julie; Staels, Bart; Lefebvre, Philippe; Eeckhoute, Jérôme

    2015-01-01

    Cell differentiation relies on tissue-specific transcription factors (TFs) that cooperate to establish unique transcriptomes and phenotypes. However, the role of ubiquitous TFs in these processes remains poorly defined. Recently, we have shown that the CCCTC-binding factor (CTCF) is required for adipocyte differentiation through epigenomic remodelling of adipose tissue-specific enhancers and transcriptional activation of Peroxisome proliferator-activated receptor gamma (PPARG), the main driver of the adipogenic program (PPARG), and its target genes. Here, we discuss how these findings, together with the recent literature, illuminate a functional role for ubiquitous TFs in lineage-determining transcriptional networks.

  19. CXCR4 and CXCR7 play distinct roles in cardiac lineage specification and pharmacologic β-adrenergic response

    Directory of Open Access Journals (Sweden)

    Delaine K. Ceholski

    2017-08-01

    Full Text Available CXCR4 and CXCR7 are prominent G protein-coupled receptors (GPCRs for chemokine stromal cell-derived factor-1 (SDF-1/CXCL12. This study demonstrates that CXCR4 and CXCR7 induce differential effects during cardiac lineage differentiation and β-adrenergic response in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs. Using lentiviral vectors to ablate CXCR4 and/or CXCR7 expression, hiPSC-CMs were tested for phenotypic and functional properties due to gene knockdown. Gene expression and flow cytometry confirmed the pluripotent and cardiomyocyte phenotype of undifferentiated and differentiated hiPSCs, respectively. Although reduction of CXCR4 and CXCR7 expression resulted in a delayed cardiac phenotype, only knockdown of CXCR4 delayed the spontaneous beating of hiPSC-CMs. Knockdown of CXCR4 and CXCR7 differentially altered calcium transients and β-adrenergic response in hiPSC-CMs. In engineered cardiac tissues, depletion of CXCR4 or CXCR7 had opposing effects on developed force and chronotropic response to β-agonists. This work demonstrates distinct roles for the SDF-1/CXCR4 or CXCR7 network in hiPSC-derived ventricular cardiomyocyte specification, maturation and function.

  20. Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause.

    Science.gov (United States)

    Van Oudenhove, Jennifer J; Grandy, Rodrigo A; Ghule, Prachi N; Del Rio, Roxana; Lian, Jane B; Stein, Janet L; Zaidi, Sayyed K; Stein, Gary S

    2016-07-01

    Human embryonic stem cells (hESCs) have an abbreviated G1 phase of the cell cycle that allows rapid proliferation and maintenance of pluripotency. Lengthening of G1 corresponds to loss of pluripotency during differentiation. However, precise mechanisms that link alterations in the cell cycle and early differentiation remain to be defined. We investigated initial stages of mesendodermal lineage commitment in hESCs, and observed a cell cycle pause. Transcriptome profiling identified several genes with known roles in regulation of the G2/M transition that were differentially expressed early during lineage commitment. WEE1 kinase, which blocks entry into mitosis by phosphorylating CDK1 at Y15, was the most highly expressed of these genes. Inhibition of CDK1 phosphorylation by a specific inhibitor of WEE1 restored cell cycle progression by preventing the G2 pause. Directed differentiation of hESCs revealed that cells paused during commitment to the endo- and mesodermal, but not ectodermal, lineages. Functionally, WEE1 inhibition during meso- and endodermal differentiation selectively decreased expression of definitive endodermal markers SOX17 and FOXA2. Our findings identify a novel G2 cell cycle pause that is required for endodermal differentiation and provide important new mechanistic insights into early events of lineage commitment. Stem Cells 2016;34:1765-1775. © 2016 AlphaMed Press.

  1. Translatomics combined with transcriptomics and proteomics reveals novel functional, recently evolved orphan genes in Escherichia coli O157:H7 (EHEC).

    Science.gov (United States)

    Neuhaus, Klaus; Landstorfer, Richard; Fellner, Lea; Simon, Svenja; Schafferhans, Andrea; Goldberg, Tatyana; Marx, Harald; Ozoline, Olga N; Rost, Burkhard; Kuster, Bernhard; Keim, Daniel A; Scherer, Siegfried

    2016-02-24

    Genomes of E. coli, including that of the human pathogen Escherichia coli O157:H7 (EHEC) EDL933, still harbor undetected protein-coding genes which, apparently, have escaped annotation due to their small size and non-essential function. To find such genes, global gene expression of EHEC EDL933 was examined, using strand-specific RNAseq (transcriptome), ribosomal footprinting (translatome) and mass spectrometry (proteome). Using the above methods, 72 short, non-annotated protein-coding genes were detected. All of these showed signals in the ribosomal footprinting assay indicating mRNA translation. Seven were verified by mass spectrometry. Fifty-seven genes are annotated in other enterobacteriaceae, mainly as hypothetical genes; the remaining 15 genes constitute novel discoveries. In addition, protein structure and function were predicted computationally and compared between EHEC-encoded proteins and 100-times randomly shuffled proteins. Based on this comparison, 61 of the 72 novel proteins exhibit predicted structural and functional features similar to those of annotated proteins. Many of the novel genes show differential transcription when grown under eleven diverse growth conditions suggesting environmental regulation. Three genes were found to confer a phenotype in previous studies, e.g., decreased cattle colonization. These findings demonstrate that ribosomal footprinting can be used to detect novel protein coding genes, contributing to the growing body of evidence that hypothetical genes are not annotation artifacts and opening an additional way to study their functionality. All 72 genes are taxonomically restricted and, therefore, appear to have evolved relatively recently de novo.

  2. Accurate Estimation of Fungal Diversity and Abundance through Improved Lineage-Specific Primers Optimized for Illumina Amplicon Sequencing.

    Science.gov (United States)

    Taylor, D Lee; Walters, William A; Lennon, Niall J; Bochicchio, James; Krohn, Andrew; Caporaso, J Gregory; Pennanen, Taina

    2016-12-15

    While high-throughput sequencing methods are revolutionizing fungal ecology, recovering accurate estimates of species richness and abundance has proven elusive. We sought to design internal transcribed spacer (ITS) primers and an Illumina protocol that would maximize coverage of the kingdom Fungi while minimizing nontarget eukaryotes. We inspected alignments of the 5.8S and large subunit (LSU) ribosomal genes and evaluated potential primers using PrimerProspector. We tested the resulting primers using tiered-abundance mock communities and five previously characterized soil samples. We recovered operational taxonomic units (OTUs) belonging to all 8 members in both mock communities, despite DNA abundances spanning 3 orders of magnitude. The expected and observed read counts were strongly correlated (r = 0.94 to 0.97). However, several taxa were consistently over- or underrepresented, likely due to variation in rRNA gene copy numbers. The Illumina data resulted in clustering of soil samples identical to that obtained with Sanger sequence clone library data using different primers. Furthermore, the two methods produced distance matrices with a Mantel correlation of 0.92. Nonfungal sequences comprised less than 0.5% of the soil data set, with most attributable to vascular plants. Our results suggest that high-throughput methods can produce fairly accurate estimates of fungal abundances in complex communities. Further improvements might be achieved through corrections for rRNA copy number and utilization of standardized mock communities. Fungi play numerous important roles in the environment. Improvements in sequencing methods are providing revolutionary insights into fungal biodiversity, yet accurate estimates of the number of fungal species (i.e., richness) and their relative abundances in an environmental sample (e.g., soil, roots, water, etc.) remain difficult to obtain. We present improved methods for high-throughput Illumina sequencing of the species

  3. Levels and patterns of nucleotide variation in domestication QTL regions on rice chromosome 3 suggest lineage-specific selection.

    Directory of Open Access Journals (Sweden)

    Xianfa Xie

    Full Text Available Oryza sativa or Asian cultivated rice is one of the major cereal grass species domesticated for human food use during the Neolithic. Domestication of this species from the wild grass Oryza rufipogon was accompanied by changes in several traits, including seed shattering, percent seed set, tillering, grain weight, and flowering time. Quantitative trait locus (QTL mapping has identified three genomic regions in chromosome 3 that appear to be associated with these traits. We would like to study whether these regions show signatures of selection and whether the same genetic basis underlies the domestication of different rice varieties. Fragments of 88 genes spanning these three genomic regions were sequenced from multiple accessions of two major varietal groups in O. sativa--indica and tropical japonica--as well as the ancestral wild rice species O. rufipogon. In tropical japonica, the levels of nucleotide variation in these three QTL regions are significantly lower compared to genome-wide levels, and coalescent simulations based on a complex demographic model of rice domestication indicate that these patterns are consistent with selection. In contrast, there is no significant reduction in nucleotide diversity in the homologous regions in indica rice. These results suggest that there are differences in the genetic and selective basis for domestication between these two Asian rice varietal groups.

  4. Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the T(H)17 lineage-specific transcription factor RORgamma t.

    Science.gov (United States)

    Ayyoub, Maha; Deknuydt, Florence; Raimbaud, Isabelle; Dousset, Christelle; Leveque, Lucie; Bioley, Gilles; Valmori, Danila

    2009-05-26

    Recent studies have suggested a close relationship between CD4(+)FOXP3(+) regulatory T cells (Tregs) and proinflammatory IL-17-producing T helper cells (T(H)17) expressing the lineage-specific transcription factor RORgamma t. We report here the unexpected finding that human memory Tregs secrete IL-17 ex vivo and constitutively express RORgamma t. IL-17-secreting Tregs share some phenotypic and functional features with conventional T(H)17 cells, expressing high levels of CCR4 and CCR6 and low levels of CXCR3. However, unlike conventional T(H)17 cells, they express low levels of CD161 and mostly fail to cosecrete IL-22 and TNF-alpha ex vivo. Ex vivo secretion of IL-17 and constitutive expression of RORgamma t by human memory Tregs suggest that, in addition to their well-known suppressive functions, these cells likely play additional, as yet undescribed, proinflammatory functions.

  5. Human memory FOXP3+ Tregs secrete IL-17 ex vivo and constitutively express the TH17 lineage-specific transcription factor RORγt

    Science.gov (United States)

    Ayyoub, Maha; Deknuydt, Florence; Raimbaud, Isabelle; Dousset, Christelle; Leveque, Lucie; Bioley, Gilles; Valmori, Danila

    2009-01-01

    Recent studies have suggested a close relationship between CD4+FOXP3+ regulatory T cells (Tregs) and proinflammatory IL-17-producing T helper cells (TH17) expressing the lineage-specific transcription factor RORγt. We report here the unexpected finding that human memory Tregs secrete IL-17 ex vivo and constitutively express RORγt. IL-17-secreting Tregs share some phenotypic and functional features with conventional TH17 cells, expressing high levels of CCR4 and CCR6 and low levels of CXCR3. However, unlike conventional TH17 cells, they express low levels of CD161 and mostly fail to cosecrete IL-22 and TNF-α ex vivo. Ex vivo secretion of IL-17 and constitutive expression of RORγt by human memory Tregs suggest that, in addition to their well-known suppressive functions, these cells likely play additional, as yet undescribed, proinflammatory functions. PMID:19439651

  6. Lineage-specific responses of tooth shape in murine rodents (murinae, rodentia to late Miocene dietary change in the Siwaliks of Pakistan.

    Directory of Open Access Journals (Sweden)

    Yuri Kimura

    Full Text Available Past ecological responses of mammals to climate change are recognized in the fossil record by adaptive significance of morphological variations. To understand the role of dietary behavior on functional adaptations of dental morphology in rodent evolution, we examine evolutionary change of tooth shape in late Miocene Siwalik murine rodents, which experienced a dietary shift toward C4 diets during late Miocene ecological change indicated by carbon isotopic evidence. Geometric morphometric analysis in the outline of upper first molars captures dichotomous lineages of Siwalik murines, in agreement with phylogenetic hypotheses of previous studies (two distinct clades: the Karnimata and Progonomys clades, and indicates lineage-specific functional responses to mechanical properties of their diets. Tooth shapes of the two clades are similar at their sympatric origin but deviate from each other with decreasing overlap through time. Shape change in the Karnimata clade is associated with greater efficiency of propalinal chewing for tough diets than in the Progonomys clade. Larger body mass in Karnimata may be related to exploitation of lower-quality food items, such as grasses, than in smaller-bodied Progonomys. The functional and ecophysiological aspects of Karnimata exploiting C4 grasses are concordant with their isotopic dietary preference relative to Progonomys. Lineage-specific selection was differentially greater in Karnimata, and a faster rate of shape change toward derived Karnimata facilitated inclusion of C4 grasses in the diet. Sympatric speciation in these clades is most plausibly explained by interspecific competition on resource utilization between the two, based on comparisons of our results with the carbon isotope data. Interspecific competition with Karnimata may have suppressed morphological innovation of the Progonomys clade. Pairwise analyses of morphological and carbon isotope data can uncover ecological causes of sympatric speciation

  7. NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that inhibits GSK3β resulting in the stabilization of MYCN in human neuroblastomas.

    Directory of Open Access Journals (Sweden)

    Yusuke Suenaga

    2014-01-01

    Full Text Available The rearrangement of pre-existing genes has long been thought of as the major mode of new gene generation. Recently, de novo gene birth from non-genic DNA was found to be an alternative mechanism to generate novel protein-coding genes. However, its functional role in human disease remains largely unknown. Here we show that NCYM, a cis-antisense gene of the MYCN oncogene, initially thought to be a large non-coding RNA, encodes a de novo evolved protein regulating the pathogenesis of human cancers, particularly neuroblastoma. The NCYM gene is evolutionally conserved only in the taxonomic group containing humans and chimpanzees. In primary human neuroblastomas, NCYM is 100% co-amplified and co-expressed with MYCN, and NCYM mRNA expression is associated with poor clinical outcome. MYCN directly transactivates both NCYM and MYCN mRNA, whereas NCYM stabilizes MYCN protein by inhibiting the activity of GSK3β, a kinase that promotes MYCN degradation. In contrast to MYCN transgenic mice, neuroblastomas in MYCN/NCYM double transgenic mice were frequently accompanied by distant metastases, behavior reminiscent of human neuroblastomas with MYCN amplification. The NCYM protein also interacts with GSK3β, thereby stabilizing the MYCN protein in the tumors of the MYCN/NCYM double transgenic mice. Thus, these results suggest that GSK3β inhibition by NCYM stabilizes the MYCN protein both in vitro and in vivo. Furthermore, the survival of MYCN transgenic mice bearing neuroblastoma was improved by treatment with NVP-BEZ235, a dual PI3K/mTOR inhibitor shown to destabilize MYCN via GSK3β activation. In contrast, tumors caused in MYCN/NCYM double transgenic mice showed chemo-resistance to the drug. Collectively, our results show that NCYM is the first de novo evolved protein known to act as an oncopromoting factor in human cancer, and suggest that de novo evolved proteins may functionally characterize human disease.

  8. An evolvable oestrogen receptor activity sensor: development of a modular system for integrating multiple genes into the yeast genome

    NARCIS (Netherlands)

    Fox, J.E.; Bridgham, J.T.; Bovee, T.F.H.; Thornton, J.W.

    2007-01-01

    To study a gene interaction network, we developed a gene-targeting strategy that allows efficient and stable genomic integration of multiple genetic constructs at distinct target loci in the yeast genome. This gene-targeting strategy uses a modular plasmid with a recyclable selectable marker and a

  9. Gene expression analysis of parthenogenetic embryonic development of the pea aphid, Acyrthosiphon pisum, suggests that aphid parthenogenesis evolved from meiotic oogenesis.

    Science.gov (United States)

    Srinivasan, Dayalan G; Abdelhady, Ahmed; Stern, David L

    2014-01-01

    Aphids exhibit a form of phenotypic plasticity, called polyphenism, in which genetically identical females reproduce sexually during one part of the life cycle and asexually (via parthenogenesis) during the remainder of the life cycle. The molecular basis for aphid parthenogenesis is unknown. Cytological observations of aphid parthenogenesis suggest that asexual oogenesis evolved either through a modification of meiosis or from a mitotic process. As a test of these alternatives, we assessed the expression levels and expression patterns of canonical meiotic recombination and germline genes in the sexual and asexual ovaries of the pea aphid, Acyrthosiphon pisum. We observed expression of all meiosis genes in similar patterns in asexual and sexual ovaries, with the exception that some genes encoding Argonaute-family members were not expressed in sexual ovaries. In addition, we observed that asexual aphid tissues accumulated unspliced transcripts of Spo11, whereas sexual aphid tissues accumulated primarily spliced transcripts. In situ hybridization revealed Spo11 transcript in sexual germ cells and undetectable levels of Spo11 transcript in asexual germ cells. We also found that an obligately asexual strain of pea aphid produced little spliced Spo11 transcript. Together, these results suggest that parthenogenetic oogenesis evolved from a meiosis-like, and not a mitosis-like, process and that the aphid reproductive polyphenism may involve a modification of Spo11 gene activity.

  10. Intrinsic incompatibilities evolving as a by-product of divergent ecological selection: Considering them in empirical studies on divergence with gene flow.

    Science.gov (United States)

    Kulmuni, J; Westram, A M

    2017-06-01

    The possibility of intrinsic barriers to gene flow is often neglected in empirical research on local adaptation and speciation with gene flow, for example when interpreting patterns observed in genome scans. However, we draw attention to the fact that, even with gene flow, divergent ecological selection may generate intrinsic barriers involving both ecologically selected and other interacting loci. Mechanistically, the link between the two types of barriers may be generated by genes that have multiple functions (i.e., pleiotropy), and/or by gene interaction networks. Because most genes function in complex networks, and their evolution is not independent of other genes, changes evolving in response to ecological selection can generate intrinsic barriers as a by-product. A crucial question is to what extent such by-product barriers contribute to divergence and speciation-that is whether they stably reduce gene flow. We discuss under which conditions by-product barriers may increase isolation. However, we also highlight that, depending on the conditions (e.g., the amount of gene flow and the strength of selection acting on the intrinsic vs. the ecological barrier component), the intrinsic incompatibility may actually destabilize barriers to gene flow. In practice, intrinsic barriers generated as a by-product of divergent ecological selection may generate peaks in genome scans that cannot easily be interpreted. We argue that empirical studies on divergence with gene flow should consider the possibility of both ecological and intrinsic barriers. Future progress will likely come from work combining population genomic studies, experiments quantifying fitness and molecular studies on protein function and interactions. © 2017 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  11. Clustering of two genes putatively involved in cyanate detoxification evolved recently and independently in multiple fungal lineages

    Science.gov (United States)

    Fungi that have the enzymes cyanase and carbonic anhydrase show a limited capacity to detoxify cyanate, a fungicide employed by both plants and humans. Here, we describe a novel two-gene cluster that comprises duplicated cyanase and carbonic anhydrase copies, which we name the CCA gene cluster, trac...

  12. The Asian Rice Gall Midge (Orseolia oryzae Mitogenome Has Evolved Novel Gene Boundaries and Tandem Repeats That Distinguish Its Biotypes.

    Directory of Open Access Journals (Sweden)

    Isha Atray

    Full Text Available The complete mitochondrial genome of the Asian rice gall midge, Orseolia oryzae (Diptera; Cecidomyiidae was sequenced, annotated and analysed in the present study. The circular genome is 15,286 bp with 13 protein-coding genes, 22 tRNAs and 2 ribosomal RNA genes, and a 578 bp non-coding control region. All protein coding genes used conventional start codons and terminated with a complete stop codon. The genome presented many unusual features: (1 rearrangement in the order of tRNAs as well as protein coding genes; (2 truncation and unusual secondary structures of tRNAs; (3 presence of two different repeat elements in separate non-coding regions; (4 presence of one pseudo-tRNA gene; (5 inversion of the rRNA genes; (6 higher percentage of non-coding regions when compared with other insect mitogenomes. Rearrangements of the tRNAs and protein coding genes are explained on the basis of tandem duplication and random loss model and why intramitochondrial recombination is a better model for explaining rearrangements in the O. oryzae mitochondrial genome is discussed. Furthermore, we evaluated the number of iterations of the tandem repeat elements found in the mitogenome. This led to the identification of genetic markers capable of differentiating rice gall midge biotypes and the two Orseolia species investigated.

  13. Clustering of two genes putatively involved in cyanate detoxification evolved recently and independently in multiple fungal lineages.

    Science.gov (United States)

    Elmore, M Holly; McGary, Kriston L; Wisecaver, Jennifer H; Slot, Jason C; Geiser, David M; Sink, Stacy; O'Donnell, Kerry; Rokas, Antonis

    2015-02-06

    Fungi that have the enzymes cyanase and carbonic anhydrase show a limited capacity to detoxify cyanate, a fungicide employed by both plants and humans. Here, we describe a novel two-gene cluster that comprises duplicated cyanase and carbonic anhydrase copies, which we name the CCA gene cluster, trace its evolution across Ascomycetes, and examine the evolutionary dynamics of its spread among lineages of the Fusarium oxysporum species complex (hereafter referred to as the FOSC), a cosmopolitan clade of purportedly clonal vascular wilt plant pathogens. Phylogenetic analysis of fungal cyanase and carbonic anhydrase genes reveals that the CCA gene cluster arose independently at least twice and is now present in three lineages, namely Cochliobolus lunatus, Oidiodendron maius, and the FOSC. Genome-wide surveys within the FOSC indicate that the CCA gene cluster varies in copy number across isolates, is always located on accessory chromosomes, and is absent in FOSC's closest relatives. Phylogenetic reconstruction of the CCA gene cluster in 163 FOSC strains from a wide variety of hosts suggests a recent history of rampant transfers between isolates. We hypothesize that the independent formation of the CCA gene cluster in different fungal lineages and its spread across FOSC strains may be associated with resistance to plant-produced cyanates or to use of cyanate fungicides in agriculture. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  14. Evidence That Loss-of-Function Filaggrin Gene Mutations Evolved in Northern Europeans to Favor Intracutaneous Vitamin D3 Production

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Bikle, Daniel D; Elias, Peter M

    2014-01-01

    Skin pigmentation lightened progressively to a variable extent, as modern humans emigrated out of Africa, but extreme lightening occurred only in northern Europeans. Yet, loss of pigmentation alone cannot suffice to sustain cutaneous vitamin D3 (VD3) formation at the high latitudes of northern...... UV-B penetration and intracutaneous VD3 formation, the latitude-dependent gradient in FLG mutations, likely together with other concurrent mutations in VD3 metabolic pathways, provide a non-pigment-based mechanism that sustains higher levels of circulating VD3 in northern Europeans. At the time...... that FLG mutations evolved, xerosis due to FLG deficiency was a lesser price to pay for enhanced VD3 production. Yet, the increase in FLG mutations has inadvertently contributed to an epidemic of atopic diseases that has emerged in recent decades....

  15. The Insect Chemoreceptor Superfamily in Drosophila pseudoobscura: Molecular Evolution of Ecologically-Relevant Genes Over 25 Million Years

    Science.gov (United States)

    Robertson, Hugh M.

    2009-01-01

    The insect chemoreceptor superfamily, consisting of the odorant receptor (Or) and gustatory receptor (Gr) families, exhibits patterns of evolution ranging from highly conserved proteins to lineage-specific gene subfamily expansions when compared across insect suborders and orders. Here their evolution across the timespan of 25 million years is examined which yield orthologous divergences ranging from 5–50%. They also reveal the beginnings of lineage-specific gene subfamilies as multiple duplications of particular gene lineages in either or both Drosophila melanogaster and D. pseudoobscura (Frolova and Astaurov) (Diptera: Drosophilidae). Gene losses and pseudogenes are similarly evident in both lineages, and even in closer comparisons of D. melanogaster with D. yakuba, leaving these species with roughly similar numbers of chemoreceptors despite considerable gene turnover. The large range of divergences and gene duplications provide abundant raw material for studies of structure and function in this novel superfamily, which contains proteins that evolved to bind specific ligands that mediate much of the ecology and mating behavior of insects. PMID:19613461

  16. Maintaining evolvability

    Indian Academy of Sciences (India)

    2008-12-23

    Dec 23, 2008 ... inherit a disproportionate number of genes acting additively on the trait, thus increasing genetic variance. For these ... Keywords. polygenes; additive genetic variance; epistasis; dominance; selection response; quantitative genetics. Journal of ..... The effect of epistasis on homozygous viability depression in.

  17. AS3MT-mediated tolerance to arsenic evolved by multiple independent horizontal gene transfers from bacteria to eukaryotes

    DEFF Research Database (Denmark)

    Palmgren, Michael Broberg; Engström, Karin; Hallström, Björn M

    2017-01-01

    the evolutionary origin of AS3MT and assessed the ability of different genotypes to produce methylated arsenic metabolites. Phylogenetic analysis suggests that multiple, independent horizontal gene transfers between different bacteria, and from bacteria to eukaryotes, increased tolerance to environmental arsenic...

  18. Targeted disruption in mice of a neural stem cell-maintaining, KRAB-Zn finger-encoding gene that has rapidly evolved in the human lineage.

    Directory of Open Access Journals (Sweden)

    Huan-Chieh Chien

    Full Text Available Understanding the genetic basis of the physical and behavioral traits that separate humans from other primates is a challenging but intriguing topic. The adaptive functions of the expansion and/or reduction in human brain size have long been explored. From a brain transcriptome project we have identified a KRAB-Zn finger protein-encoding gene (M003-A06 that has rapidly evolved since the human-chimpanzee separation. Quantitative RT-PCR analysis of different human tissues indicates that M003-A06 expression is enriched in the human fetal brain in addition to the fetal heart. Furthermore, analysis with use of immunofluorescence staining, neurosphere culturing and Western blotting indicates that the mouse ortholog of M003-A06, Zfp568, is expressed mainly in the embryonic stem (ES cells and fetal as well as adult neural stem cells (NSCs. Conditional gene knockout experiments in mice demonstrates that Zfp568 is both an NSC maintaining- and a brain size-regulating gene. Significantly, molecular genetic analyses show that human M003-A06 consists of 2 equilibrated allelic types, H and C, one of which (H is human-specific. Combined contemporary genotyping and database mining have revealed interesting genetic associations between the different genotypes of M003-A06 and the human head sizes. We propose that M003-A06 is likely one of the genes contributing to the uniqueness of the human brain in comparison to other higher primates.

  19. The Fast-Evolving phy-2 Gene Modulates Sexual Development in Response to Light in the Model Fungus Neurospora crassa

    OpenAIRE

    Wang, Zheng; Li, Ning; Li, Jigang; Dunlap, Jay C.; Trail, Frances; Townsend, Jeffrey P.

    2016-01-01

    ABSTRACT Rapid responses to changes in incident light are critical to the guidance of behavior and development in most species. Phytochrome light receptors in particular play key roles in bacterial physiology and plant development, but their functions and regulation are less well understood in fungi. Nevertheless, genome-wide expression measurements provide key information that can guide experiments that reveal how genes respond to environmental signals and clarify their role in development. ...

  20. Chloroplast biogenesis-associated nuclear genes: Control by plastid signals evolved prior to their regulation as part of photomorphogenesis.

    Directory of Open Access Journals (Sweden)

    Alison C HIlls

    2015-12-01

    Full Text Available The assembly of photosynthetically-competent chloroplasts occurs in angiosperm seedlings when first exposed to light, and is due to the control by light of photosynthesis-associated nuclear genes (PhANGs, also dependent upon plastid-to-nucleus biogenic communication signals. The relationship between light- and plastid signal-regulation of PhANGs is close but poorly understood. In contrast, many conifers green in the dark and the promoter of a pine PhANG, Lhcb, is active in the dark in tobacco. Here we show that the activity of this promoter in tobacco is sensitive to plastid photobleaching, or to the inhibition of plastid translation in the light or the dark, and the same interventions reduce expression of the native gene in pine seedlings, demonstrating classic plastid biogenic signalling in gymnosperms. Furthermore, Arabidopsis mutations causing defective plastid biogenesis suppress the effect in darkness of mutations in COP1 and DET1, repressors of photomorphogenesis, for the expression of several PhANGs but not a photosynthesis-unrelated, light-regulated gene. GLK transcriptional regulators mediate the response of LHCB but not of other tested PhANGs. We propose gain of the ability by repressors of photomorphogenesis to suppress the response of PhANG promoters to positive plastid biogenic signals in the dark to have contributed to the evolution of light control of chloroplast biogenesis.

  1. Evolution of the Vertebrate Resistin Gene Family.

    Directory of Open Access Journals (Sweden)

    Qingda Hu

    Full Text Available Resistin (encoded by Retn was previously identified in rodents as a hormone associated with diabetes; however human resistin is instead linked to inflammation. Resistin is a member of a small gene family that includes the resistin-like peptides (encoded by Retnl genes in mammals. Genomic searches of available genome sequences of diverse vertebrates and phylogenetic analyses were conducted to determine the size and origin of the resistin-like gene family. Genes encoding peptides similar to resistin were found in Mammalia, Sauria, Amphibia, and Actinistia (coelacanth, a lobe-finned fish, but not in Aves or fish from Actinopterygii, Chondrichthyes, or Agnatha. Retnl originated by duplication and transposition from Retn on the early mammalian lineage after divergence of the platypus, but before the placental and marsupial mammal divergence. The resistin-like gene family illustrates an instance where the locus of origin of duplicated genes can be identified, with Retn continuing to reside at this location. Mammalian species typically have a single copy Retn gene, but are much more variable in their numbers of Retnl genes, ranging from 0 to 9. Since Retn is located at the locus of origin, thus likely retained the ancestral expression pattern, largely maintained its copy number, and did not display accelerated evolution, we suggest that it is more likely to have maintained an ancestral function, while Retnl, which transposed to a new location, displays accelerated evolution, and shows greater variability in gene number, including gene loss, likely evolved new, but potentially lineage-specific, functions.

  2. Functional Desaturase Fads1 (Δ5) and Fads2 (Δ6) Orthologues Evolved before the Origin of Jawed Vertebrates

    Science.gov (United States)

    Castro, Luís Filipe Costa; Monroig, Óscar; Leaver, Michael J.; Wilson, Jonathan; Cunha, Isabel; Tocher, Douglas R.

    2012-01-01

    Long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic (ARA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids are essential components of biomembranes, particularly in neural tissues. Endogenous synthesis of ARA, EPA and DHA occurs from precursor dietary essential fatty acids such as linoleic and α-linolenic acid through elongation and Δ5 and Δ6 desaturations. With respect to desaturation activities some noteworthy differences have been noted in vertebrate classes. In mammals, the Δ5 activity is allocated to the Fads1 gene, while Fads2 is a Δ6 desaturase. In contrast, teleosts show distinct combinations of desaturase activities (e.g. bifunctional or separate Δ5 and Δ6 desaturases) apparently allocated to Fads2-type genes. To determine the timing of Fads1-Δ5 and Fads2-Δ6 evolution in vertebrates we used a combination of comparative and functional genomics with the analysis of key phylogenetic species. Our data show that Fads1 and Fads2 genes with Δ5 and Δ6 activities respectively, evolved before gnathostome radiation, since the catshark Scyliorhinus canicula has functional orthologues of both gene families. Consequently, the loss of Fads1 in teleosts is a secondary episode, while the existence of Δ5 activities in the same group most likely occurred through independent mutations into Fads2 type genes. Unexpectedly, we also establish that events of Fads1 gene expansion have taken place in birds and reptiles. Finally, a fourth Fads gene (Fads4) was found with an exclusive occurrence in mammalian genomes. Our findings enlighten the history of a crucially important gene family in vertebrate fatty acid metabolism and physiology and provide an explanation of how observed lineage-specific gene duplications, losses and diversifications might be linked to habitat-specific food web structures in different environments and over geological timescales. PMID:22384110

  3. Functional desaturase Fads1 (Δ5 and Fads2 (Δ6 orthologues evolved before the origin of jawed vertebrates.

    Directory of Open Access Journals (Sweden)

    Luís Filipe Costa Castro

    Full Text Available Long-chain polyunsaturated fatty acids (LC-PUFAs such as arachidonic (ARA, eicosapentaenoic (EPA and docosahexaenoic (DHA acids are essential components of biomembranes, particularly in neural tissues. Endogenous synthesis of ARA, EPA and DHA occurs from precursor dietary essential fatty acids such as linoleic and α-linolenic acid through elongation and Δ5 and Δ6 desaturations. With respect to desaturation activities some noteworthy differences have been noted in vertebrate classes. In mammals, the Δ5 activity is allocated to the Fads1 gene, while Fads2 is a Δ6 desaturase. In contrast, teleosts show distinct combinations of desaturase activities (e.g. bifunctional or separate Δ5 and Δ6 desaturases apparently allocated to Fads2-type genes. To determine the timing of Fads1-Δ5 and Fads2-Δ6 evolution in vertebrates we used a combination of comparative and functional genomics with the analysis of key phylogenetic species. Our data show that Fads1 and Fads2 genes with Δ5 and Δ6 activities respectively, evolved before gnathostome radiation, since the catshark Scyliorhinus canicula has functional orthologues of both gene families. Consequently, the loss of Fads1 in teleosts is a secondary episode, while the existence of Δ5 activities in the same group most likely occurred through independent mutations into Fads2 type genes. Unexpectedly, we also establish that events of Fads1 gene expansion have taken place in birds and reptiles. Finally, a fourth Fads gene (Fads4 was found with an exclusive occurrence in mammalian genomes. Our findings enlighten the history of a crucially important gene family in vertebrate fatty acid metabolism and physiology and provide an explanation of how observed lineage-specific gene duplications, losses and diversifications might be linked to habitat-specific food web structures in different environments and over geological timescales.

  4. Conserved loci of leaf and stem rust fungi of wheat share synteny interrupted by lineage-specific influx of repeat elements

    Directory of Open Access Journals (Sweden)

    Fellers John P

    2013-01-01

    Full Text Available Abstract Background Wheat leaf rust (Puccinia triticina Eriks; Pt and stem rust fungi (P. graminis f.sp. tritici; Pgt are significant economic pathogens having similar host ranges and life cycles, but different alternate hosts. The Pt genome, currently estimated at 135 Mb, is significantly larger than Pgt, at 88 Mb, but the reason for the expansion is unknown. Three genomic loci of Pt conserved proteins were characterized to gain insight into gene content, genome complexity and expansion. Results A bacterial artificial chromosome (BAC library was made from P. triticina race 1, BBBD and probed with Pt homologs of genes encoding two predicted Pgt secreted effectors and a DNA marker mapping to a region of avirulence. Three BACs, 103 Kb, 112 Kb, and 166 Kb, were sequenced, assembled, and open reading frames were identified. Orthologous genes were identified in Pgt and local conservation of gene order (microsynteny was observed. Pairwise protein identities ranged from 26 to 99%. One Pt BAC, containing a RAD18 ortholog, shares syntenic regions with two Pgt scaffolds, which could represent both haplotypes of Pgt. Gene sequence is diverged between the species as well as within the two haplotypes. In all three BAC clones, gene order is locally conserved, however, gene shuffling has occurred relative to Pgt. These regions are further diverged by differing insertion loci of LTR-retrotransposon, Gypsy, Copia, Mutator, and Harbinger mobile elements. Uncharacterized Pt open reading frames were also found; these proteins are high in lysine and similar to multiple proteins in Pgt. Conclusions The three Pt loci are conserved in gene order, with a range of gene sequence divergence. Conservation of predicted haustoria expressed secreted protein genes between Pt and Pgt is extended to the more distant poplar rust, Melampsora larici-populina. The loci also reveal that genome expansion in Pt is in part due to higher occurrence of repeat-elements in this species.

  5. Changes in G+C content of a neutrally evolving gene under a non-reversible dynamics measured by computer simulations based on experimental evolution data

    Directory of Open Access Journals (Sweden)

    Adriana Brunstein

    2004-01-01

    Full Text Available To evaluate the effects of non-reversibility on compositional base changes and the distribution of branch lengths along a phylogeny, we extended, by means of computer simulations, our previous sequential PCR in vitro evolution experiment. In that study a 18S rRNA gene evolved neutrally for 280 generations and a homogeneous non-stationary model of base substitution based on a non-reversible dynamics was built from the in vitro evolution data to describe the observed pattern of nucleotide substitutions. Here, the process was extended to 840 generations without selection, using the model parameters calculated from the in vitro evolution experiment. We observed that under a non-reversible model the G+C content of the sequences significantly increases when compared to simulations with a reversible model. The values of mean and variance of the branch lengths are reduced under a non-reversible dynamics although they follow a Poisson distribution. We conclude that the major implication of non-reversibility is the overall decrease of branch lengths, although no transition from a stochastic to an ordered process is observed. According to our model the result of this neutral process will be the increase in the G+C content of the descendant sequences with an overall decrease in the frequency of substitutions.

  6. Polo-Like Kinase 2 is Dynamically Regulated to Coordinate Proliferation and Early Lineage Specification Downstream of Yes-Associated Protein 1 in Cardiac Progenitor Cells.

    Science.gov (United States)

    Mochizuki, Michika; Lorenz, Vera; Ivanek, Robert; Della Verde, Giacomo; Gaudiello, Emanuele; Marsano, Anna; Pfister, Otmar; Kuster, Gabriela M

    2017-10-24

    Recent studies suggest that adult cardiac progenitor cells (CPCs) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPCs are ill defined. Extracellular matrix components are important instructors of cell fate. Using laminin and fibronectin, we induced two slightly distinct CPC phenotypes differing in proliferation rate and commitment status and analyzed the early transcriptomic response to CPC adhesion (Yes-associated protein (YAP) conserved signature and TEA domain family member 1 (TEAD1)-related genes. This early gene regulation was preceded by the rapid cytosolic sequestration and degradation of YAP on laminin. Among the most strongly regulated genes was polo-like kinase 2 (Plk2). Plk2 expression depended on YAP stability and was enhanced in CPCs transfected with a nuclear-targeted mutant YAP. Phenotypically, the early downregulation of Plk2 on laminin was succeeded by lower cell proliferation, enhanced lineage gene expression (24 hours), and facilitated differentiation (3 weeks) compared with fibronectin. Finally, overexpression of Plk2 enhanced CPC proliferation and knockdown of Plk2 induced the expression of lineage genes. Plk2 acts as coordinator of cell proliferation and early lineage commitment in CPCs. The rapid downregulation of Plk2 on YAP inactivation marks a switch towards enhanced commitment and facilitated differentiation. These findings link early gene regulation to cell fate and provide novel insights into how CPC proliferation and differentiation are orchestrated. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. A genome survey sequencing of the Java mouse deer (Tragulus javanicus) adds new aspects to the evolution of lineage specific retrotransposons in Ruminantia (Cetartiodactyla)

    DEFF Research Database (Denmark)

    Gallus, S; Kumar, V; Bertelsen, Mads Frost

    2015-01-01

    Ruminantia, the ruminating, hoofed mammals (cow, deer, giraffe and allies) are an unranked artiodactylan clade. Around 50-60 million years ago the BovB retrotransposon entered the ancestral ruminantian genome through horizontal gene transfer. A survey genome screen using 454-pyrosequencing...

  8. Clonal analysis of kit ligand a functional expression reveals lineage-specific competence to promote melanocyte rescue in the mutant regenerating caudal fin.

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    Robert C Tryon

    Full Text Available The study of regeneration in an in vivo vertebrate system has the potential to reveal targetable genes and pathways that could improve our ability to heal and repair damaged tissue. We have developed a system for clonal labeling of discrete cell lineages and independently inducing gene expression under control of the heat shock promoter in the zebrafish caudal fin. Consequently we are able to test the affects of overexpressing a single gene in the context of regeneration within each of the nine different cell lineage classes that comprise the caudal fin. This can test which lineage is necessary or sufficient to provide gene function. As a first example to demonstrate this approach, we explored which lineages were competent to functionally express the kit ligand a protein as assessed by the local complementation of the mutation in the sparse-like (kitlgatc244b background. We show that dermal fibroblast expression of kit ligand a robustly supports the rescue of melanocytes in the regenerating caudal fin. kit ligand a expression from skin and osteoblasts results in more modest and variable rescue of melanocytes, while lateral line expression was unable to complement the mutation.

  9. Lineage-specific variations of congruent evolution among DNA sequences from three genomes, and relaxed selective constraints on rbcL in Cryptomonas (Cryptophyceae).

    Science.gov (United States)

    Hoef-Emden, Kerstin; Tran, Hoang-Dung; Melkonian, Michael

    2005-10-18

    Plastid-bearing cryptophytes like Cryptomonas contain four genomes in a cell, the nucleus, the nucleomorph, the plastid genome and the mitochondrial genome. Comparative phylogenetic analyses encompassing DNA sequences from three different genomes were performed on nineteen photosynthetic and four colorless Cryptomonas strains. Twenty-three rbcL genes and fourteen nuclear SSU rDNA sequences were newly sequenced to examine the impact of photosynthesis loss on codon usage in the rbcL genes, and to compare the rbcL gene phylogeny in terms of tree topology and evolutionary rates with phylogenies inferred from nuclear ribosomal DNA (concatenated SSU rDNA, ITS2 and partial LSU rDNA), and nucleomorph SSU rDNA. Largely congruent branching patterns and accelerated evolutionary rates were found in nucleomorph SSU rDNA and rbcL genes in a clade that consisted of photosynthetic and colorless species suggesting a coevolution of the two genomes. The extremely accelerated rates in the rbcL phylogeny correlated with a shift from selection to mutation drift in codon usage of two-fold degenerate NNY codons comprising the amino acids asparagine, aspartate, histidine, phenylalanine, and tyrosine. Cysteine was the sole exception. The shift in codon usage seemed to follow a gradient from early diverging photosynthetic to late diverging photosynthetic or heterotrophic taxa along the branches. In the early branching taxa, codon preferences were changed in one to two amino acids, whereas in the late diverging taxa, including the colorless strains, between four and five amino acids showed changes in codon usage. Nucleomorph and plastid gene phylogenies indicate that loss of photosynthesis in the colorless Cryptomonas strains examined in this study possibly was the result of accelerated evolutionary rates that started already in photosynthetic ancestors. Shifts in codon usage are usually considered to be caused by changes in functional constraints and in gene expression levels. Thus, the

  10. Evolvable synthetic neural system

    Science.gov (United States)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  11. Defects in the synthetic pathway prevent DIF-1 mediated stalk lineage specification cascade in the non-differentiating social amoeba, Acytostelium subglobosum.

    Science.gov (United States)

    Mohri, Kurato; Hata, Takashi; Kikuchi, Haruhisa; Oshima, Yoshiteru; Urushihara, Hideko

    2014-05-29

    Separation of somatic cells from germ-line cells is a crucial event for multicellular organisms, but how this step was achieved during evolution remains elusive. In Dictyostelium discoideum and many other dictyostelid species, solitary amoebae gather and form a multicellular fruiting body in which germ-line spores and somatic stalk cells differentiate, whereas in Acytostelium subglobosum, acellular stalks form and all aggregated amoebae become spores. In this study, because most D. discoideum genes known to be required for stalk cell differentiation have homologs in A. subglobosum, we inferred functional variations in these genes and examined conservation of the stalk cell specification cascade of D. discoideum mediated by the polyketide differentiation-inducing factor-1 (DIF-1) in A. subglobosum. Through heterologous expression of A. subglobosum orthologs of DIF-1 biosynthesis genes in D. discoideum, we confirmed that two of the three genes were functional equivalents, while DIF-methyltransferase (As-dmtA) involved at the final step of DIF-1 synthesis was not. In fact, DIF-1 activity was undetectable in A. subglobosum lysates and amoebae of this species were not responsive to DIF-1, suggesting a lack of DIF-1 production in this species. On the other hand, the molecular function of an A. subglobosum ortholog of DIF-1 responsive transcription factor was equivalent with that of D. discoideum and inhibition of polyketide synthesis caused developmental arrest in A. subglobosum, which could not be rescued by DIF-1 addition. These results suggest that non-DIF-1 polyketide cascades involving downstream transcription factors are required for fruiting body development of A. subglobosum. © 2014. Published by The Company of Biologists Ltd.

  12. The Insect Chemoreceptor Superfamily in Drosophila pseudoobscura: Molecular Evolution of Ecologically-Relevant Genes Over 25 Million Years

    OpenAIRE

    Robertson, Hugh M.

    2009-01-01

    The insect chemoreceptor superfamily, consisting of the odorant receptor (Or) and gustatory receptor (Gr) families, exhibits patterns of evolution ranging from highly conserved proteins to lineage-specific gene subfamily expansions when compared across insect suborders and orders. Here their evolution across the timespan of 25 million years is examined which yield orthologous divergences ranging from 5–50%. They also reveal the beginnings of lineage-specific gene subfamilies as multiple dupli...

  13. A morphogenetic survey on ciliate plankton from a mountain lake pinpoints the necessity of lineage-specific barcode markers in microbial ecology.

    Science.gov (United States)

    Stoeck, Thorsten; Breiner, Hans-Werner; Filker, Sabine; Ostermaier, Veronika; Kammerlander, Barbara; Sonntag, Bettina

    2014-02-01

    Analyses of high-throughput environmental sequencing data have become the 'gold-standard' to address fundamental questions of microbial diversity, ecology and biogeography. Findings that emerged from sequencing are, e.g. the discovery of the extensive 'rare microbial biosphere' and its potential function as a seed-bank. Even though applied since several years, results from high-throughput environmental sequencing have hardly been validated. We assessed how well pyrosequenced amplicons [the hypervariable eukaryotic V4 region of the small subunit ribosomal RNA (SSU rRNA) gene] reflected morphotype ciliate plankton. Moreover, we assessed if amplicon sequencing had the potential to detect the annual ciliate plankton stock. In both cases, we identified significant quantitative and qualitative differences. Our study makes evident that taxon abundance distributions inferred from amplicon data are highly biased and do not mirror actual morphotype abundances at all. Potential reasons included cell losses after fixation, cryptic morphotypes, resting stages, insufficient sequence data availability of morphologically described species and the unsatisfying resolution of the V4 SSU rRNA fragment for accurate taxonomic assignments. The latter two underline the necessity of barcoding initiatives for eukaryotic microbes to better and fully exploit environmental amplicon data sets, which then will also allow studying the potential of seed-bank taxa as a buffer for environmental changes. © 2013 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.

  14. Lineage-specific SoxR-mediated Regulation of an Endoribonuclease Protects Non-enteric Bacteria from Redox-active Compounds.

    Science.gov (United States)

    Kim, Jisun; Park, Chulwoo; Imlay, James A; Park, Woojun

    2017-01-06

    Bacteria use redox-sensitive transcription factors to coordinate responses to redox stress. The [2Fe-2S] cluster-containing transcription factor SoxR is particularly tuned to protect cells against redox-active compounds (RACs). In enteric bacteria, SoxR is paired with a second transcription factor, SoxS, that activates downstream effectors. However, SoxS is absent in non-enteric bacteria, raising questions as to how SoxR functions. Here, we first show that SoxR of Acinetobacter oleivorans displayed similar activation profiles in response to RACs as did its homolog from Escherichia coli but controlled a different set of target genes, including sinE, which encodes an endoribonuclease. Expression, gel mobility shift, and mutational analyses indicated that sinE is a direct target of SoxR. Redox potentials and permeability of RACs determined optimal sinE induction. Bioinformatics suggested that only a few γ- and β-proteobacteria might have SoxR-regulated sinE Purified SinE, in the presence of Mg(2+) ions, degrades rRNAs, thus inhibiting protein synthesis. Similarly, pretreatment of cells with RACs demonstrated a role for SinE in promoting persistence in the presence of antibiotics that inhibit protein synthesis. Our data improve our understanding of the physiology of soil microorganisms by suggesting that both non-enteric SoxR and its target SinE play protective roles in the presence of RACs and antibiotics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Development of a real-time QPCR assay for the detection of RV2 lineage-specific rhadinoviruses in macaques and baboons

    Directory of Open Access Journals (Sweden)

    Thouless Margaret E

    2005-01-01

    Full Text Available Abstract Background Two distinct lineages of rhadinoviruses related to Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8 have been identified in macaques and other Old World non-human primates. We have developed a real-time quantitative PCR (QPCR assay using a TaqMan probe to differentially detect and quantitate members of the rhadinovirus-2 (RV2 lineage. PCR primers were derived from sequences within ORF 60 and the adjacent ORF 59/60 intergenic region which were highly conserved between the macaque RV2 rhadinoviruses, rhesus rhadinovirus (RRV and Macaca nemestrina rhadinovirus-2 (MneRV2. These primers showed little similarity to the corresponding sequences of the macaque RV1 rhadinoviruses, retroperitoneal fibromatosis herpesvirus Macaca nemestrina (RFHVMn and Macaca mulatta (RFHVMm. To determine viral loads per cell, an additional TaqMan QPCR assay was developed to detect the single copy cellular oncostatin M gene. Results We show that the RV2 QPCR assay is linear from less than 2 to more than 300,000 copies using MneRV2 DNA, and is non-reactive with RFHVMn DNA up to 1 billion DNA templates per reaction. RV2 loads ranging from 6 to 2,300 viral genome equivalent copies per 106 cells were detected in PBMC from randomly sampled macaques from the Washington National Primate Research Center. Screening tissue from other primate species, including another macaque, Macaca fascicularis, and a baboon, Papio cynocephalus, revealed the presence of novel rhadinoviruses, MfaRV2 and PcyRV2, respectively. Sequence comparison and phylogenetic analysis confirmed their inclusion within the RV2 lineage of KSHV-like rhadinoviruses. Conclusions We describe a QPCR assay which provides a quick and sensitive method for quantitating rhadinoviruses belonging to the RV2 lineage of KSHV-like rhadinoviruses found in a variety of macaque species commonly used for biomedical research. While this assay broadly detects different RV2 rhadinovirus species, it is unreactive with

  16. Evolution of Hemoglobin and Its Genes

    Science.gov (United States)

    Hardison, Ross C.

    2012-01-01

    Insights into the evolution of hemoglobins and their genes are an abundant source of ideas regarding hemoglobin function and regulation of globin gene expression. This article presents the multiple genes and gene families encoding human globins, summarizes major events in the evolution of the hemoglobin gene clusters, and discusses how these studies provide insights into regulation of globin genes. Although the genes in and around the α-like globin gene complex are relatively stable, the β-like globin gene clusters are more dynamic, showing evidence of transposition to a new locus and frequent lineage-specific expansions and deletions. The cis-regulatory modules controlling levels and timing of gene expression are a mix of conserved and lineage-specific DNA, perhaps reflecting evolutionary constraint on core regulatory functions shared broadly in mammals and adaptive fine-tuning in different orders of mammals. PMID:23209182

  17. Fat: an evolving issue

    Directory of Open Access Journals (Sweden)

    John R. Speakman

    2012-09-01

    Work on obesity is evolving, and obesity is a consequence of our evolutionary history. In the space of 50 years, we have become an obese species. The reasons why can be addressed at a number of different levels. These include separating between whether the primary cause lies on the food intake or energy expenditure side of the energy balance equation, and determining how genetic and environmental effects contribute to weight variation between individuals. Opinion on whether increased food intake or decreased energy expenditure drives the obesity epidemic is still divided, but recent evidence favours the idea that food intake, rather than altered expenditure, is most important. There is more of a consensus that genetics explains most (probably around 65% of weight variation between individuals. Recent advances in genome-wide association studies have identified many polymorphisms that are linked to obesity, yet much of the genetic variance remains unexplained. Finding the causes of this unexplained variation will be an impetus of genetic and epigenetic research on obesity over the next decade. Many environmental factors – including gut microbiota, stress and endocrine disruptors – have been linked to the risk of developing obesity. A better understanding of gene-by-environment interactions will also be key to understanding obesity in the years to come.

  18. Duplicated paralogous genes subject to positive selection in the genome of Trypanosoma brucei.

    Directory of Open Access Journals (Sweden)

    Richard D Emes

    2008-05-01

    Full Text Available Whole genome studies have highlighted duplicated genes as important substrates for adaptive evolution. We have investigated adaptive evolution in this class of genes in the human parasite Trypanosoma brucei, as indicated by the ratio of non-synonymous (amino-acid changing to synonymous (amino acid retaining nucleotide substitution rates.We have identified duplicated genes that are most rapidly evolving in this important human parasite. This is the first attempt to investigate adaptive evolution in this species at the codon level. We identify 109 genes within 23 clusters of paralogous gene expansions to be subject to positive selection.Genes identified include surface antigens in both the mammalian and insect host life cycle stage suggesting that competitive interaction is not solely with the adaptive immune system of the mammalian host. Also surface transporters related to drug resistance and genes related to developmental progression are detected. We discuss how adaptive evolution of these genes may highlight lineage specific processes essential for parasite survival. We also discuss the implications of adaptive evolution of these targets for parasite biology and control.

  19. Lineage specification in the early mouse embryo.

    Science.gov (United States)

    Lanner, Fredrik

    2014-02-01

    Before the mammalian embryo is ready to implant in the uterine wall, the single cell zygote must divide and differentiate into three distinct tissues; trophectoderm (prospective placenta), primitive endoderm (prospective yolk sac), and pluripotent epiblast cells which will form the embryo proper. In this review I will discuss our current understanding of how positional information, cell polarization, signaling pathways, and transcription factor networks converge to drive and regulate the progressive segregation of the first three cell types in the mouse embryo. © 2013 Published by Elsevier Inc.

  20. Evolution of the F-Box Gene Family in Euarchontoglires: Gene Number Variation and Selection Patterns

    Science.gov (United States)

    Wang, Ailan; Fu, Mingchuan; Jiang, Xiaoqian; Mao, Yuanhui; Li, Xiangchen; Tao, Shiheng

    2014-01-01

    F-box proteins are substrate adaptors used by the SKP1–CUL1–F-box protein (SCF) complex, a type of E3 ubiquitin ligase complex in the ubiquitin proteasome system (UPS). SCF-mediated ubiquitylation regulates proteolysis of hundreds of cellular proteins involved in key signaling and disease systems. However, our knowledge of the evolution of the F-box gene family in Euarchontoglires is limited. In the present study, 559 F-box genes and nine related pseudogenes were identified in eight genomes. Lineage-specific gene gain and loss events occurred during the evolution of Euarchontoglires, resulting in varying F-box gene numbers ranging from 66 to 81 among the eight species. Both tandem duplication and retrotransposition were found to have contributed to the increase of F-box gene number, whereas mutation in the F-box domain was the main mechanism responsible for reduction in the number of F-box genes, resulting in a balance of expansion and contraction in the F-box gene family. Thus, the Euarchontoglire F-box gene family evolved under a birth-and-death model. Signatures of positive selection were detected in substrate-recognizing domains of multiple F-box proteins, and adaptive changes played a role in evolution of the Euarchontoglire F-box gene family. In addition, single nucleotide polymorphism (SNP) distributions were found to be highly non-random among different regions of F-box genes in 1092 human individuals, with domain regions having a significantly lower number of non-synonymous SNPs. PMID:24727786

  1. Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens" and "Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans".

    Science.gov (United States)

    Currat, Mathias; Excoffier, Laurent; Maddison, Wayne; Otto, Sarah P; Ray, Nicolas; Whitlock, Michael C; Yeaman, Sam

    2006-07-14

    Mekel-Bobrov et al. and Evans et al. (Reports, 9 Sept. 2005, p. 1720 and p. 1717, respectively) examined sequence data from modern humans within two gene regions associated with brain development, ASPM and microcephalin, and concluded that selection of these genes must be ongoing. We show that models of human history that include both population growth and spatial structure can generate the observed patterns without selection.

  2. Metschnikowia Species Share a Pool of Diverse rRNA Genes Differing in Regions That Determine Hairpin-Loop Structures and Evolve by Reticulation.

    Directory of Open Access Journals (Sweden)

    Matthias Sipiczki

    Full Text Available Modern taxonomy of yeasts is mainly based on phylogenetic analysis of conserved DNA and protein sequences. By far the most frequently used sequences are those of the repeats of the chromosomal rDNA array. It is generally accepted that the rDNA repeats of a genome have identical sequences due to the phenomenon of sequence homogenisation and can thus be used for identification and barcoding of species. Here we show that the rDNA arrays of the type strains of Metschnikowia andauensis and M. fructicola are not homogenised. Both have arrays consisting of diverse repeats that differ from each other in the D1/D2 domains by up to 18 and 25 substitutions. The variable sites are concentrated in two regions that correspond to back-folding stretches of hairpin loops in the predicted secondary structure of the RNA molecules. The substitutions do not alter significantly the overall hairpin-loop structure due to wobble base pairing at sites of C-T transitions and compensatory mutations in the complementary strand of the hairpin stem. The phylogenetic and network analyses of the cloned sequences revealed that the repeats had not evolved in a vertical tree-like way but reticulation might have shaped the rDNA arrays of both strains. The neighbour-net analysis of all cloned sequences of the type strains and the database sequences of different strains further showed that these species share a continuous pool of diverse repeats that appear to evolve by reticulate evolution.

  3. Comparative genomic analysis of SET domain family reveals the origin, expansion, and putative function of the arthropod-specific SmydA genes as histone modifiers in insects

    Science.gov (United States)

    Jiang, Feng; Liu, Qing; Wang, Yanli; Zhang, Jie; Wang, Huimin; Song, Tianqi; Yang, Meiling

    2017-01-01

    Abstract The SET domain is an evolutionarily conserved motif present in histone lysine methyltransferases, which are important in the regulation of chromatin and gene expression in animals. In this study, we searched for SET domain–containing genes (SET genes) in all of the 147 arthropod genomes sequenced at the time of carrying out this experiment to understand the evolutionary history by which SET domains have evolved in insects. Phylogenetic and ancestral state reconstruction analysis revealed an arthropod-specific SET gene family, named SmydA, that is ancestral to arthropod animals and specifically diversified during insect evolution. Considering that pseudogenization is the most probable fate of the new emerging gene copies, we provided experimental and evolutionary evidence to demonstrate their essential functions. Fluorescence in situ hybridization analysis and in vitro methyltransferase activity assays showed that the SmydA-2 gene was transcriptionally active and retained the original histone methylation activity. Expression knockdown by RNA interference significantly increased mortality, implying that the SmydA genes may be essential for insect survival. We further showed predominantly strong purifying selection on the SmydA gene family and a potential association between the regulation of gene expression and insect phenotypic plasticity by transcriptome analysis. Overall, these data suggest that the SmydA gene family retains essential functions that may possibly define novel regulatory pathways in insects. This work provides insights into the roles of lineage-specific domain duplication in insect evolution. PMID:28444351

  4. High mature grain phytase activity in the Triticeae has evolved by duplication followed by neofunctionalization of the purple acid phosphatase phytase (PAPhy) gene

    DEFF Research Database (Denmark)

    Madsen, Claus Krogh; Dionisio, Giuseppe; Holme, Inger

    2013-01-01

    The phytase activity in food and feedstuffs is an important nutritional parameter. Members of the Triticeae tribe accumulate purple acid phosphatase phytases (PAPhy) during grain filling. This accumulation elevates mature grain phytase activities (MGPA) up to levels between ~650 FTU/kg for barley...... maintained the archaic function and drives expression during germination. Brachypodium is the only sequenced Poaceae sharing the PAPhy duplication. As for the Triticeae, the duplication is reflected in a high MGPA of ~4200 FTU/kg in Brachypodium. The sequence conservation of the paralogous loci...... on Brachypodium chromosomes 1 and 2 does not extend beyond the PAPhy gene. The results indicate that a single-gene segmental duplication may have enabled the evolution of high MGPA by creating functional redundancy of the parent PAPhy gene. This implies that similar MGPA levels may be out of reach in breeding...

  5. Evolving digital ecological networks.

    Directory of Open Access Journals (Sweden)

    Miguel A Fortuna

    Full Text Available "It is hard to realize that the living world as we know it is just one among many possibilities" [1]. Evolving digital ecological networks are webs of interacting, self-replicating, and evolving computer programs (i.e., digital organisms that experience the same major ecological interactions as biological organisms (e.g., competition, predation, parasitism, and mutualism. Despite being computational, these programs evolve quickly in an open-ended way, and starting from only one or two ancestral organisms, the formation of ecological networks can be observed in real-time by tracking interactions between the constantly evolving organism phenotypes. These phenotypes may be defined by combinations of logical computations (hereafter tasks that digital organisms perform and by expressed behaviors that have evolved. The types and outcomes of interactions between phenotypes are determined by task overlap for logic-defined phenotypes and by responses to encounters in the case of behavioral phenotypes. Biologists use these evolving networks to study active and fundamental topics within evolutionary ecology (e.g., the extent to which the architecture of multispecies networks shape coevolutionary outcomes, and the processes involved.

  6. Mentoring: An Evolving Relationship.

    Science.gov (United States)

    Block, Michelle; Florczak, Kristine L

    2017-04-01

    The column concerns itself with mentoring as an evolving relationship between mentor and mentee. The collegiate mentoring model, the transformational transcendence model, and the humanbecoming mentoring model are considered in light of a dialogue with mentors at a Midwest university and conclusions are drawn.

  7. Measurably evolving populations

    DEFF Research Database (Denmark)

    Drummond, Alexei James; Pybus, Oliver George; Rambaut, Andrew

    2003-01-01

    processes through time. Populations for which such studies are possible � measurably evolving populations (MEPs) � are characterized by sufficiently long or numerous sampled sequences and a fast mutation rate relative to the available range of sequence sampling times. The impact of sequences sampled through...... understanding of evolutionary processes in diverse organisms, from viruses to vertebrates....

  8. Conserved regulation of p53 network dosage by microRNA-125b occurs through evolving miRNA-target gene pairs.

    Directory of Open Access Journals (Sweden)

    Minh T N Le

    2011-09-01

    Full Text Available MicroRNAs regulate networks of genes to orchestrate cellular functions. MiR-125b, the vertebrate homologue of the Caenorhabditis elegans microRNA lin-4, has been implicated in the regulation of neural and hematopoietic stem cell homeostasis, analogous to how lin-4 regulates stem cells in C. elegans. Depending on the cell context, miR-125b has been proposed to regulate both apoptosis and proliferation. Because the p53 network is a central regulator of both apoptosis and proliferation, the dual roles of miR-125b raise the question of what genes in the p53 network might be regulated by miR-125b. By using a gain- and loss-of-function screen for miR-125b targets in humans, mice, and zebrafish and by validating these targets with the luciferase assay and a novel miRNA pull-down assay, we demonstrate that miR-125b directly represses 20 novel targets in the p53 network. These targets include both apoptosis regulators like Bak1, Igfbp3, Itch, Puma, Prkra, Tp53inp1, Tp53, Zac1, and also cell-cycle regulators like cyclin C, Cdc25c, Cdkn2c, Edn1, Ppp1ca, Sel1l, in the p53 network. We found that, although each miRNA-target pair was seldom conserved, miR-125b regulation of the p53 pathway is conserved at the network level. Our results lead us to propose that miR-125b buffers and fine-tunes p53 network activity by regulating the dose of both proliferative and apoptotic regulators, with implications for tissue stem cell homeostasis and oncogenesis.

  9. Minimal Effect of Ectopic Gene Conversion Among Recent Duplicates in Four Mammalian Genomes

    OpenAIRE

    McGrath, Casey L.; Casola, Claudio; Hahn, Matthew W.

    2009-01-01

    Gene conversion between duplicated genes has been implicated in homogenization of gene families and reassortment of variation among paralogs. If conversion is common, this process could lead to errors in gene tree inference and subsequent overestimation of rates of gene duplication. After performing simulations to assess our power to detect gene conversion events, we determined rates of conversion among young, lineage-specific gene duplicates in four mammal species: human, rhesus macaque, mou...

  10. A case study for effects of operational taxonomic units from intracellular endoparasites and ciliates on the eukaryotic phylogeny: phylogenetic position of the haptophyta in analyses of multiple slowly evolving genes.

    Directory of Open Access Journals (Sweden)

    Hisayoshi Nozaki

    Full Text Available Recent multigene phylogenetic analyses have contributed much to our understanding of eukaryotic phylogeny. However, the phylogenetic positions of various lineages within the eukaryotes have remained unresolved or in conflict between different phylogenetic studies. These phylogenetic ambiguities might have resulted from mixtures or integration from various factors including limited taxon sampling, missing data in the alignment, saturations of rapidly evolving genes, mixed analyses of short- and long-branched operational taxonomic units (OTUs, intracellular endoparasite and ciliate OTUs with unusual substitution etc. In order to evaluate the effects from intracellular endoparasite and ciliate OTUs co-analyzed on the eukaryotic phylogeny and simplify the results, we here used two different sets of data matrices of multiple slowly evolving genes with small amounts of missing data and examined the phylogenetic position of the secondary photosynthetic chromalveolates Haptophyta, one of the most abundant groups of oceanic phytoplankton and significant primary producers. In both sets, a robust sister relationship between Haptophyta and SAR (stramenopiles, alveolates, rhizarians, or SA [stramenopiles and alveolates] was resolved when intracellular endoparasite/ciliate OTUs were excluded, but not in their presence. Based on comparisons of character optimizations on a fixed tree (with a clade composed of haptophytes and SAR or SA, disruption of the monophyly between haptophytes and SAR (or SA in the presence of intracellular endoparasite/ciliate OTUs can be considered to be a result of multiple evolutionary reversals of character positions that supported the synapomorphy of the haptophyte and SAR (or SA clade in the absence of intracellular endoparasite/ciliate OTUs.

  11. EVOLVE 2014 International Conference

    CERN Document Server

    Tantar, Emilia; Sun, Jian-Qiao; Zhang, Wei; Ding, Qian; Schütze, Oliver; Emmerich, Michael; Legrand, Pierrick; Moral, Pierre; Coello, Carlos

    2014-01-01

    This volume encloses research articles that were presented at the EVOLVE 2014 International Conference in Beijing, China, July 1–4, 2014.The book gathers contributions that emerged from the conference tracks, ranging from probability to set oriented numerics and evolutionary computation; all complemented by the bridging purpose of the conference, e.g. Complex Networks and Landscape Analysis, or by the more application oriented perspective. The novelty of the volume, when considering the EVOLVE series, comes from targeting also the practitioner’s view. This is supported by the Machine Learning Applied to Networks and Practical Aspects of Evolutionary Algorithms tracks, providing surveys on new application areas, as in the networking area and useful insights in the development of evolutionary techniques, from a practitioner’s perspective. Complementary to these directions, the conference tracks supporting the volume, follow on the individual advancements of the subareas constituting the scope of the confe...

  12. Unravelling the Evolution of the Allatostatin-Type A, KISS and Galanin Peptide-Receptor Gene Families in Bilaterians: Insights from Anopheles Mosquitoes.

    Directory of Open Access Journals (Sweden)

    Rute C Felix

    Full Text Available Allatostatin type A receptors (AST-ARs are a group of G-protein coupled receptors activated by members of the FGL-amide (AST-A peptide family that inhibit food intake and development in arthropods. Despite their physiological importance the evolution of the AST-A system is poorly described and relatively few receptors have been isolated and functionally characterised in insects. The present study provides a comprehensive analysis of the origin and comparative evolution of the AST-A system. To determine how evolution and feeding modified the function of AST-AR the duplicate receptors in Anopheles mosquitoes, were characterised. Phylogeny and gene synteny suggested that invertebrate AST-A receptors and peptide genes shared a common evolutionary origin with KISS/GAL receptors and ligands. AST-ARs and KISSR emerged from a common gene ancestor after the divergence of GALRs in the bilaterian genome. In arthropods, the AST-A system evolved through lineage-specific events and the maintenance of two receptors in the flies and mosquitoes (Diptera was the result of a gene duplication event. Speciation of Anopheles mosquitoes affected receptor gene organisation and characterisation of AST-AR duplicates (GPRALS1 and 2 revealed that in common with other insects, the mosquito receptors were activated by insect AST-A peptides and the iCa2+-signalling pathway was stimulated. GPRALS1 and 2 were expressed mainly in mosquito midgut and ovaries and transcript abundance of both receptors was modified by feeding. A blood meal strongly up-regulated expression of both GPRALS in the midgut (p < 0.05 compared to glucose fed females. Based on the results we hypothesise that the AST-A system in insects shared a common origin with the vertebrate KISS system and may also share a common function as an integrator of metabolism and reproduction.AST-A and KISS/GAL receptors and ligands shared common ancestry prior to the protostome-deuterostome divergence. Phylogeny and gene

  13. Evolvable Neural Software System

    Science.gov (United States)

    Curtis, Steven A.

    2009-01-01

    The Evolvable Neural Software System (ENSS) is composed of sets of Neural Basis Functions (NBFs), which can be totally autonomously created and removed according to the changing needs and requirements of the software system. The resulting structure is both hierarchical and self-similar in that a given set of NBFs may have a ruler NBF, which in turn communicates with other sets of NBFs. These sets of NBFs may function as nodes to a ruler node, which are also NBF constructs. In this manner, the synthetic neural system can exhibit the complexity, three-dimensional connectivity, and adaptability of biological neural systems. An added advantage of ENSS over a natural neural system is its ability to modify its core genetic code in response to environmental changes as reflected in needs and requirements. The neural system is fully adaptive and evolvable and is trainable before release. It continues to rewire itself while on the job. The NBF is a unique, bilevel intelligence neural system composed of a higher-level heuristic neural system (HNS) and a lower-level, autonomic neural system (ANS). Taken together, the HNS and the ANS give each NBF the complete capabilities of a biological neural system to match sensory inputs to actions. Another feature of the NBF is the Evolvable Neural Interface (ENI), which links the HNS and ANS. The ENI solves the interface problem between these two systems by actively adapting and evolving from a primitive initial state (a Neural Thread) to a complicated, operational ENI and successfully adapting to a training sequence of sensory input. This simulates the adaptation of a biological neural system in a developmental phase. Within the greater multi-NBF and multi-node ENSS, self-similar ENI s provide the basis for inter-NBF and inter-node connectivity.

  14. Evolution and functional divergence of NLRP genes in mammalian reproductive systems

    Directory of Open Access Journals (Sweden)

    Monget Philippe

    2009-08-01

    Full Text Available Abstract Background NLRPs (Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing Proteins are members of NLR (Nod-like receptors protein family. Recent researches have shown that NLRP genes play important roles in both mammalian innate immune system and reproductive system. Several of NLRP genes were shown to be specifically expressed in the oocyte in mammals. The aim of the present work was to study how these genes evolved and diverged after their duplication, as well as whether natural selection played a role during their evolution. Results By using in silico methods, we have evaluated the evolution and functional divergence of NLRP genes, in particular of mouse reproduction-related Nlrp genes. We found that (1 major NLRP genes have been duplicated before the divergence of mammals, with certain lineage-specific duplications in primates (NLRP7 and 11 and in rodents (Nlrp1, 4 and 9 duplicates; (2 tandem duplication events gave rise to a mammalian reproduction-related NLRP cluster including NLRP2, 4, 5, 7, 8, 9, 11, 13 and 14 genes; (3 the function of mammalian oocyte-specific NLRP genes (NLRP4, 5, 9 and 14 might have diverged during gene evolution; (4 recent segmental duplications concerning Nlrp4 copies and vomeronasal 1 receptor encoding genes (V1r have been undertaken in the mouse; and (5 duplicates of Nlrp4 and 9 in the mouse might have been subjected to adaptive evolution. Conclusion In conclusion, this study brings us novel information on the evolution of mammalian reproduction-related NLRPs. On the one hand, NLRP genes duplicated and functionally diversified in mammalian reproductive systems (such as NLRP4, 5, 9 and 14. On the other hand, during evolution, different lineages adapted to develop their own NLRP genes, particularly in reproductive function (such as the specific expansion of Nlrp4 and Nlrp9 in the mouse.

  15. Regolith Evolved Gas Analyzer

    Science.gov (United States)

    Hoffman, John H.; Hedgecock, Jud; Nienaber, Terry; Cooper, Bonnie; Allen, Carlton; Ming, Doug

    2000-01-01

    The Regolith Evolved Gas Analyzer (REGA) is a high-temperature furnace and mass spectrometer instrument for determining the mineralogical composition and reactivity of soil samples. REGA provides key mineralogical and reactivity data that is needed to understand the soil chemistry of an asteroid, which then aids in determining in-situ which materials should be selected for return to earth. REGA is capable of conducting a number of direct soil measurements that are unique to this instrument. These experimental measurements include: (1) Mass spectrum analysis of evolved gases from soil samples as they are heated from ambient temperature to 900 C; and (2) Identification of liberated chemicals, e.g., water, oxygen, sulfur, chlorine, and fluorine. REGA would be placed on the surface of a near earth asteroid. It is an autonomous instrument that is controlled from earth but does the analysis of regolith materials automatically. The REGA instrument consists of four primary components: (1) a flight-proven mass spectrometer, (2) a high-temperature furnace, (3) a soil handling system, and (4) a microcontroller. An external arm containing a scoop or drill gathers regolith samples. A sample is placed in the inlet orifice where the finest-grained particles are sifted into a metering volume and subsequently moved into a crucible. A movable arm then places the crucible in the furnace. The furnace is closed, thereby sealing the inner volume to collect the evolved gases for analysis. Owing to the very low g forces on an asteroid compared to Mars or the moon, the sample must be moved from inlet to crucible by mechanical means rather than by gravity. As the soil sample is heated through a programmed pattern, the gases evolved at each temperature are passed through a transfer tube to the mass spectrometer for analysis and identification. Return data from the instrument will lead to new insights and discoveries including: (1) Identification of the molecular masses of all of the gases

  16. Gene isoform specificity through enhancer-associated antisense transcription.

    Directory of Open Access Journals (Sweden)

    Courtney S Onodera

    Full Text Available Enhancers and antisense RNAs play key roles in transcriptional regulation through differing mechanisms. Recent studies have demonstrated that enhancers are often associated with non-coding RNAs (ncRNAs, yet the functional role of these enhancer:ncRNA associations is unclear. Using RNA-Sequencing to interrogate the transcriptomes of undifferentiated mouse embryonic stem cells (mESCs and their derived neural precursor cells (NPs, we identified two novel enhancer-associated antisense transcripts that appear to control isoform-specific expression of their overlapping protein-coding genes. In each case, an enhancer internal to a protein-coding gene drives an antisense RNA in mESCs but not in NPs. Expression of the antisense RNA is correlated with expression of a shorter isoform of the associated sense gene that is not present when the antisense RNA is not expressed. We demonstrate that expression of the antisense transcripts as well as expression of the short sense isoforms correlates with enhancer activity at these two loci. Further, overexpression and knockdown experiments suggest the antisense transcripts regulate expression of their associated sense genes via cis-acting mechanisms. Interestingly, the protein-coding genes involved in these two examples, Zmynd8 and Brd1, share many functional domains, yet their antisense ncRNAs show no homology to each other and are not present in non-murine mammalian lineages, such as the primate lineage. The lack of homology in the antisense ncRNAs indicates they have evolved independently of each other and suggests that this mode of lineage-specific transcriptional regulation may be more widespread in other cell types and organisms. Our findings present a new view of enhancer action wherein enhancers may direct isoform-specific expression of genes through ncRNA intermediates.

  17. Molecular adaptation of telomere associated genes in mammals.

    Science.gov (United States)

    Morgan, Claire C; Mc Cartney, Ann M; Donoghue, Mark T A; Loughran, Noeleen B; Spillane, Charles; Teeling, Emma C; O'Connell, Mary J

    2013-11-15

    Placental mammals display a huge range of life history traits, including size, longevity, metabolic rate and germ line generation time. Although a number of general trends have been proposed between these traits, there are exceptions that warrant further investigation. Species such as naked mole rat, human and certain bat species all exhibit extreme longevity with respect to body size. It has long been established that telomeres and telomere maintenance have a clear role in ageing but it has not yet been established whether there is evidence for adaptation in telomere maintenance proteins that could account for increased longevity in these species. Here we carry out a molecular investigation of selective pressure variation, specifically focusing on telomere associated genes across placental mammals. In general we observe a large number of instances of positive selection acting on telomere genes. Although these signatures of selection overall are not significantly correlated with either longevity or body size we do identify positive selection in the microbat species Myotis lucifugus in functionally important regions of the telomere maintenance genes DKC1 and TERT, and in naked mole rat in the DNA repair gene BRCA1. These results demonstrate the multifarious selective pressures acting across the mammal phylogeny driving lineage-specific adaptations of telomere associated genes. Our results show that regardless of the longevity of a species, these proteins have evolved under positive selection thereby removing increased longevity as the single selective force driving this rapid rate of evolution. However, evidence of molecular adaptations specific to naked mole rat and Myotis lucifugus highlight functionally significant regions in genes that may alter the way in which telomeres are regulated and maintained in these longer-lived species.

  18. Quantifying evolvability in small biological networks

    Energy Technology Data Exchange (ETDEWEB)

    Nemenman, Ilya [Los Alamos National Laboratory; Mugler, Andrew [COLUMBIA UNIV; Ziv, Etay [COLUMBIA UNIV; Wiggins, Chris H [COLUMBIA UNIV

    2008-01-01

    The authors introduce a quantitative measure of the capacity of a small biological network to evolve. The measure is applied to a stochastic description of the experimental setup of Guet et al. (Science 2002, 296, pp. 1466), treating chemical inducers as functional inputs to biochemical networks and the expression of a reporter gene as the functional output. The authors take an information-theoretic approach, allowing the system to set parameters that optimise signal processing ability, thus enumerating each network's highest-fidelity functions. All networks studied are highly evolvable by the measure, meaning that change in function has little dependence on change in parameters. Moreover, each network's functions are connected by paths in the parameter space along which information is not significantly lowered, meaning a network may continuously change its functionality without completely losing it along the way. This property further underscores the evolvability of the networks.

  19. Evolving Concepts of Asthma

    Science.gov (United States)

    Ray, Anuradha; Wenzel, Sally E.

    2015-01-01

    Our understanding of asthma has evolved over time from a singular disease to a complex of various phenotypes, with varied natural histories, physiologies, and responses to treatment. Early therapies treated most patients with asthma similarly, with bronchodilators and corticosteroids, but these therapies had varying degrees of success. Similarly, despite initial studies that identified an underlying type 2 inflammation in the airways of patients with asthma, biologic therapies targeted toward these type 2 pathways were unsuccessful in all patients. These observations led to increased interest in phenotyping asthma. Clinical approaches, both biased and later unbiased/statistical approaches to large asthma patient cohorts, identified a variety of patient characteristics, but they also consistently identified the importance of age of onset of disease and the presence of eosinophils in determining clinically relevant phenotypes. These paralleled molecular approaches to phenotyping that developed an understanding that not all patients share a type 2 inflammatory pattern. Using biomarkers to select patients with type 2 inflammation, repeated trials of biologics directed toward type 2 cytokine pathways saw newfound success, confirming the importance of phenotyping in asthma. Further research is needed to clarify additional clinical and molecular phenotypes, validate predictive biomarkers, and identify new areas for possible interventions. PMID:26161792

  20. Evolving endoscopic surgery.

    Science.gov (United States)

    Sakai, Paulo; Faintuch, Joel

    2014-06-01

    Since the days of Albukasim in medieval Spain, natural orifices have been regarded not only as a rather repugnant source of bodily odors, fluids and excreta, but also as a convenient invitation to explore and treat the inner passages of the organism. However, surgical ingenuity needed to be matched by appropriate tools and devices. Lack of technologically advanced instrumentation was a strong deterrent during almost a millennium until recent decades when a quantum jump materialized. Endoscopic surgery is currently a vibrant and growing subspecialty, which successfully handles millions of patients every year. Additional opportunities lie ahead which might benefit millions more, however, requiring even more sophisticated apparatuses, particularly in the field of robotics, artificial intelligence, and tissue repair (surgical suturing). This is a particularly exciting and worthwhile challenge, namely of larger and safer endoscopic interventions, followed by seamless and scarless recovery. In synthesis, the future is widely open for those who use together intelligence and creativity to develop new prototypes, new accessories and new techniques. Yet there are many challenges in the path of endoscopic surgery. In this new era of robotic endoscopy, one will likely need a virtual simulator to train and assess the performance of younger doctors. More evidence will be essential in multiple evolving fields, particularly to elucidate whether more ambitious and complex pathways, such as intrathoracic and intraperitoneal surgery via natural orifice transluminal endoscopic surgery (NOTES), are superior or not to conventional techniques. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  1. Asymmetric evolving random networks

    Science.gov (United States)

    Coulomb, S.; Bauer, M.

    2003-10-01

    We generalize the Poissonian evolving random graph model of M. Bauer and D. Bernard (2003), to deal with arbitrary degree distributions. The motivation comes from biological networks, which are well-known to exhibit non Poissonian degree distributions. A node is added at each time step and is connected to the rest of the graph by oriented edges emerging from older nodes. This leads to a statistical asymmetry between incoming and outgoing edges. The law for the number of new edges at each time step is fixed but arbitrary. Thermodynamical behavior is expected when this law has a large time limit. Although (by construction) the incoming degree distributions depend on this law, this is not the case for most qualitative features concerning the size distribution of connected components, as long as the law has a finite variance. As the variance grows above 1/4, the average being < 1/2, a giant component emerges, which connects a finite fraction of the vertices. Below this threshold, the distribution of component sizes decreases algebraically with a continuously varying exponent. The transition is of infinite order, in sharp contrast with the case of static graphs. The local-in-time profiles for the components of finite size allow to give a refined description of the system.

  2. Evolving a photosynthetic organelle

    Directory of Open Access Journals (Sweden)

    Nakayama Takuro

    2012-04-01

    Full Text Available Abstract The evolution of plastids from cyanobacteria is believed to represent a singularity in the history of life. The enigmatic amoeba Paulinella and its 'recently' acquired photosynthetic inclusions provide a fascinating system through which to gain fresh insight into how endosymbionts become organelles. The plastids, or chloroplasts, of algae and plants evolved from cyanobacteria by endosymbiosis. This landmark event conferred on eukaryotes the benefits of photosynthesis - the conversion of solar energy into chemical energy - and in so doing had a huge impact on the course of evolution and the climate of Earth 1. From the present state of plastids, however, it is difficult to trace the evolutionary steps involved in this momentous development, because all modern-day plastids have fully integrated into their hosts. Paulinella chromatophora is a unicellular eukaryote that bears photosynthetic entities called chromatophores that are derived from cyanobacteria and has thus received much attention as a possible example of an organism in the early stages of organellogenesis. Recent studies have unlocked the genomic secrets of its chromatophore 23 and provided concrete evidence that the Paulinella chromatophore is a bona fide photosynthetic organelle 4. The question is how Paulinella can help us to understand the process by which an endosymbiont is converted into an organelle.

  3. Evolutionary expansion and divergence in a large family of primate-specific zinc finger transcription factor genes

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, A T; Huntley, S; Tran-Gyamfi, M; Baggott, D; Gordon, L; Stubbs, L

    2005-09-28

    Although most genes are conserved as one-to-one orthologs in different mammalian orders, certain gene families have evolved to comprise different numbers and types of protein-coding genes through independent series of gene duplications, divergence and gene loss in each evolutionary lineage. One such family encodes KRAB-zinc finger (KRAB-ZNF) genes, which are likely to function as transcriptional repressors. One KRAB-ZNF subfamily, the ZNF91 clade, has expanded specifically in primates to comprise more than 110 loci in the human genome, yielding large gene clusters in human chromosomes 19 and 7 and smaller clusters or isolated copies at other chromosomal locations. Although phylogenetic analysis indicates that many of these genes arose before the split between old world monkeys and new world monkeys, the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. The paralogous loci are distinguished by sequence divergence within their zinc finger arrays indicating a selection for proteins with different DNA binding specificities. RT-PCR and in situ hybridization data show that some of these ZNF genes can have tissue-specific expression patterns, however many KRAB-ZNFs that are near-ubiquitous could also be playing very specific roles in halting target pathways in all tissues except for a few, where the target is released by the absence of its repressor. The number of variant KRAB-ZNF proteins is increased not only because of the large number of loci, but also because many loci can produce multiple splice variants, which because of the modular structure of these genes may have separate and perhaps even conflicting regulatory roles. The lineage-specific duplication and rapid divergence of this family of transcription factor genes suggests a role in determining species-specific biological differences and the evolution of novel primate traits.

  4. Single-Cell Resolution of Temporal Gene Expression during Heart Development.

    Science.gov (United States)

    DeLaughter, Daniel M; Bick, Alexander G; Wakimoto, Hiroko; McKean, David; Gorham, Joshua M; Kathiriya, Irfan S; Hinson, John T; Homsy, Jason; Gray, Jesse; Pu, William; Bruneau, Benoit G; Seidman, J G; Seidman, Christine E

    2016-11-21

    Activation of complex molecular programs in specific cell lineages governs mammalian heart development, from a primordial linear tube to a four-chamber organ. To characterize lineage-specific, spatiotemporal developmental programs, we performed single-cell RNA sequencing of >1,200 murine cells isolated at seven time points spanning embryonic day 9.5 (primordial heart tube) to postnatal day 21 (mature heart). Using unbiased transcriptional data, we classified cardiomyocytes, endothelial cells, and fibroblast-enriched cells, thus identifying markers for temporal and chamber-specific developmental programs. By harnessing these datasets, we defined developmental ages of human and mouse pluripotent stem-cell-derived cardiomyocytes and characterized lineage-specific maturation defects in hearts of mice with heterozygous mutations in Nkx2.5 that cause human heart malformations. This spatiotemporal transcriptome analysis of heart development reveals lineage-specific gene programs underlying normal cardiac development and congenital heart disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. An evolutionary arms race between KRAB zinc finger genes 91/93 and SVA/L1 retrotransposons

    Science.gov (United States)

    Jacobs, Frank MJ; Greenberg, David; Nguyen, Ngan; Haeussler, Maximilian; Ewing, Adam D; Katzman, Sol; Paten, Benedict; Salama, Sofie R; Haussler, David

    2014-01-01

    Summary Throughout evolution, primate genomes have been modified by waves of retrotransposon insertions1,2,3. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells (mESCs), transcriptional silencing of retrotransposons requires TRIM28 (KAP1) and it’s repressive complex, which can be recruited to target sites by KRAB zinc finger proteins such as murine-specific ZFP809 which binds to integrated murine leukemia virus DNA elements and recruits KAP1 to repress them4,5. KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons6,7. However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA)8 and Long Interspersed Nuclear Element-1 (L1)9, is unknown. We find that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8-12 MYA that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until ~12.5 MYA when the L1PA3-subfamily escaped ZNF93’s restriction through purge of the ZNF93 binding site. Our data support a model where KZNF gene expansion limits the activity of newly emerged retrotransposon classes, and this is followed by mutations in these retrotransposons to evade repression, a cycle of events that could explain the rapid expansion of lineage-specific KZNF genes. PMID:25274305

  6. An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons.

    Science.gov (United States)

    Jacobs, Frank M J; Greenberg, David; Nguyen, Ngan; Haeussler, Maximilian; Ewing, Adam D; Katzman, Sol; Paten, Benedict; Salama, Sofie R; Haussler, David

    2014-12-11

    Throughout evolution primate genomes have been modified by waves of retrotransposon insertions. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, transcriptional silencing of retrotransposons requires KAP1 (also known as TRIM28) and its repressive complex, which can be recruited to target sites by KRAB zinc-finger (KZNF) proteins such as murine-specific ZFP809 which binds to integrated murine leukaemia virus DNA elements and recruits KAP1 to repress them. KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons. However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA) and long interspersed nuclear element 1 (L1), is unknown. Here we show that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8-12 million years ago that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until ∼12.5 million years ago when the L1PA3-subfamily of retrotransposons escaped ZNF93's restriction through the removal of the ZNF93-binding site. Our data support a model where KZNF gene expansion limits the activity of newly emerged retrotransposon classes, and this is followed by mutations in these retrotransposons to evade repression, a cycle of events that could explain the rapid expansion of lineage-specific KZNF genes.

  7. Diverse Cis-Regulatory Mechanisms Contribute to Expression Evolution of Tandem Gene Duplicates.

    Science.gov (United States)

    Baudouin-Gonzalez, Luís; Santos, Marília A; Tempesta, Camille; Sucena, Élio; Roch, Fernando; Tanaka, Kohtaro

    2017-12-01

    Pairs of duplicated genes generally display a combination of conserved expression patterns inherited from their unduplicated ancestor and newly acquired domains. However, how the cis-regulatory architecture of duplicated loci evolves to produce these expression patterns is poorly understood. We have directly examined the gene-regulatory evolution of two tandem duplicates, the Drosophila Ly6 genes CG9336 and CG9338, which arose at the base of the drosophilids between 40 and 60 Ma. Comparing the expression patterns of the two paralogs in four Drosophila species with that of the unduplicated ortholog in the tephritid Ceratitis capitata, we show that they diverged from each other as well as from the unduplicated ortholog. Moreover, the expression divergence appears to have occurred close to the duplication event and also more recently in a lineage-specific manner. The comparison of the tissue-specific cis-regulatory modules (CRMs) controlling the paralog expression in the four Drosophila species indicates that diverse cis-regulatory mechanisms, including the novel tissue-specific enhancers, differential inactivation, and enhancer sharing, contributed to the expression evolution. Our analysis also reveals a surprisingly variable cis-regulatory architecture, in which the CRMs driving conserved expression domains change in number, location, and specificity. Altogether, this study provides a detailed historical account that uncovers a highly dynamic picture of how the paralog expression patterns and their underlying cis-regulatory landscape evolve. We argue that our findings will encourage studying cis-regulatory evolution at the whole-locus level to understand how interactions between enhancers and other regulatory levels shape the evolution of gene expression. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  8. Natural selection promotes antigenic evolvability

    NARCIS (Netherlands)

    Graves, C.J.; Ros, V.I.D.; Stevenson, B.; Sniegowski, P.D.; Brisson, D.

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide

  9. Disgust: Evolved function and structure

    NARCIS (Netherlands)

    Tybur, J.M.; Lieberman, D.; Kurzban, R.; DeScioli, P.

    2013-01-01

    Interest in and research on disgust has surged over the past few decades. The field, however, still lacks a coherent theoretical framework for understanding the evolved function or functions of disgust. Here we present such a framework, emphasizing 2 levels of analysis: that of evolved function and

  10. Evolving virtual creatures and catapults.

    Science.gov (United States)

    Chaumont, Nicolas; Egli, Richard; Adami, Christoph

    2007-01-01

    We present a system that can evolve the morphology and the controller of virtual walking and block-throwing creatures (catapults) using a genetic algorithm. The system is based on Sims' work, implemented as a flexible platform with an off-the-shelf dynamics engine. Experiments aimed at evolving Sims-type walkers resulted in the emergence of various realistic gaits while using fairly simple objective functions. Due to the flexibility of the system, drastically different morphologies and functions evolved with only minor modifications to the system and objective function. For example, various throwing techniques evolved when selecting for catapults that propel a block as far as possible. Among the strategies and morphologies evolved, we find the drop-kick strategy, as well as the systematic invention of the principle behind the wheel, when allowing mutations to the projectile.

  11. Metabolic memory: Evolving concepts.

    Science.gov (United States)

    Misra, Anoop; Bloomgarden, Zachary

    2018-03-01

    to standard control. However, the UKPDS blood pressure control trial showed a reduction in complications, but no difference between the intervention and control groups was seen during the follow-up of this portion of the study, suggesting that no such "memory" exists for these interventions. The molecular mechanisms underlying these long-term effects of prior periods of better or worse glycemic control continue to be investigated. Extended periods of exposure to high glucose levels persistently dysregulated fibrotic and inflammatory genes in endothelial and vascular smooth muscle cells. Furthermore, epigenetic processes may contribute to metabolic memory, with evidence that post-translational histone methylation and changes in microRNA may persist after exposure to high glucose levels is terminated. In this context, it is of note that the zebrafish model of T1D exhibits regeneration of the pancreas, becoming euglycemic after a period of hyperglycemia, but with evidence in this model that delay in skin wound healing persists indefinitely even after multiple rounds of fin regeneration, suggesting a long-lasting adverse effect of prior hyperglycemia. Such epigenetic differences were reported in genes related to the nuclear factor-κB inflammatory pathway and to diabetes complications in a study of intensive versus conventional treatment patients followed from the DCCT. A further mechanism that has been suggested is a role of dysregulated mitochondrial biogenesis contributing to deterioration of retinopathy even after a period of good glycemic control continues. Interestingly, in this issue of the Journal, Pantalone et al. present a study that touches upon our first question, failing to find a relationship between the HbA1c level measured at the time of diabetes diagnosis and subsequent outcome. The study analyzed relationships between glycemic control and complications among >30 000 people with newly diagnosed T2D followed for the subsequent decade. Might the level of

  12. The complete genome sequencing of Prevotella intermedia strain OMA14 and a subsequent fine-scale, intra-species genomic comparison reveal an unusual amplification of conjugative and mobile transposons and identify a novel Prevotella-lineage-specific repeat.

    Science.gov (United States)

    Naito, Mariko; Ogura, Yoshitoshi; Itoh, Takehiko; Shoji, Mikio; Okamoto, Masaaki; Hayashi, Tetsuya; Nakayama, Koji

    2016-02-01

    Prevotella intermedia is a pathogenic bacterium involved in periodontal diseases. Here, we present the complete genome sequence of a clinical strain, OMA14, of this bacterium along with the results of comparative genome analysis with strain 17 of the same species whose genome has also been sequenced, but not fully analysed yet. The genomes of both strains consist of two circular chromosomes: the larger chromosomes are similar in size and exhibit a high overall linearity of gene organizations, whereas the smaller chromosomes show a significant size variation and have undergone remarkable genome rearrangements. Unique features of the Pre. intermedia genomes are the presence of a remarkable number of essential genes on the second chromosomes and the abundance of conjugative and mobilizable transposons (CTns and MTns). The CTns/MTns are particularly abundant in the second chromosomes, involved in its extensive genome rearrangement, and have introduced a number of strain-specific genes into each strain. We also found a novel 188-bp repeat sequence that has been highly amplified in Pre. intermedia and are specifically distributed among the Pre. intermedia-related species. These findings expand our understanding of the genetic features of Pre. intermedia and the roles of CTns and MTns in the evolution of bacteria. © The Author 2015. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.

  13. Optimization as side-effect of evolving allelopathic diversity

    NARCIS (Netherlands)

    Pagie, L.; Hogeweg, P.

    2001-01-01

    Many bacteria carry gene complexes that code for a toxin-antidote pair, e.g. colicin systems. Such gene complexes can be advantageous for its host by killing competitor bacteria while the antidote protects the host. However, in order to evolve a novel and useful toxin first a proper antidote must

  14. When did oxygenic photosynthesis evolve?

    National Research Council Canada - National Science Library

    Roger Buick

    2008-01-01

    ...2.4 Ga ago, but when the photosynthetic oxygen production began is debatable. However, geological and geochemical evidence from older sedimentary rocks indicates that oxygenic photosynthesis evolved well before this oxygenation event...

  15. Marshal: Maintaining Evolving Models Project

    Data.gov (United States)

    National Aeronautics and Space Administration — SIFT proposes to design and develop the Marshal system, a mixed-initiative tool for maintaining task models over the course of evolving missions. Marshal-enabled...

  16. Natural selection promotes antigenic evolvability.

    Science.gov (United States)

    Graves, Christopher J; Ros, Vera I D; Stevenson, Brian; Sniegowski, Paul D; Brisson, Dustin

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish chronic infections.

  17. Natural selection promotes antigenic evolvability.

    Directory of Open Access Journals (Sweden)

    Christopher J Graves

    Full Text Available The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide an experimentally tractable system to test whether natural selection has favored mechanisms that increase evolvability. Many antigenic variation systems consist of paralogous unexpressed 'cassettes' that recombine into an expression site to rapidly alter the expressed protein. Importantly, the magnitude of antigenic change is a function of the genetic diversity among the unexpressed cassettes. Thus, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We used the Lyme disease bacterium, Borrelia burgdorferi, as a model to test the prediction that natural selection favors amino acid diversity among unexpressed vls cassettes and thereby promotes evolvability in a primary surface antigen, VlsE. The hypothesis that diversity among vls cassettes is favored by natural selection was supported in each B. burgdorferi strain analyzed using both classical (dN/dS ratios and Bayesian population genetic analyses of genetic sequence data. This hypothesis was also supported by the conservation of highly mutable tandem-repeat structures across B. burgdorferi strains despite a near complete absence of sequence conservation. Diversification among vls cassettes due to natural selection and mutable repeat structures promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation. The molecular evolutionary processes identified here can serve as a model for the evolution of antigenic evolvability in many pathogens which utilize similar strategies to establish

  18. The first complete chloroplast genome of the Genistoid legume Lupinus luteus: evidence for a novel major lineage-specific rearrangement and new insights regarding plastome evolution in the legume family.

    Science.gov (United States)

    Martin, Guillaume E; Rousseau-Gueutin, Mathieu; Cordonnier, Solenn; Lima, Oscar; Michon-Coudouel, Sophie; Naquin, Delphine; de Carvalho, Julie Ferreira; Aïnouche, Malika; Salmon, Armel; Aïnouche, Abdelkader

    2014-06-01

    To date chloroplast genomes are available only for members of the non-protein amino acid-accumulating clade (NPAAA) Papilionoid lineages in the legume family (i.e. Millettioids, Robinoids and the 'inverted repeat-lacking clade', IRLC). It is thus very important to sequence plastomes from other lineages in order to better understand the unusual evolution observed in this model flowering plant family. To this end, the plastome of a lupine species, Lupinus luteus, was sequenced to represent the Genistoid lineage, a noteworthy but poorly studied legume group. The plastome of L. luteus was reconstructed using Roche-454 and Illumina next-generation sequencing. Its structure, repetitive sequences, gene content and sequence divergence were compared with those of other Fabaceae plastomes. PCR screening and sequencing were performed in other allied legumes in order to determine the origin of a large inversion identified in L. luteus. The first sequenced Genistoid plastome (L. luteus: 155 894 bp) resulted in the discovery of a 36-kb inversion, embedded within the already known 50-kb inversion in the large single-copy (LSC) region of the Papilionoideae. This inversion occurs at the base or soon after the Genistoid emergence, and most probably resulted from a flip-flop recombination between identical 29-bp inverted repeats within two trnS genes. Comparative analyses of the chloroplast gene content of L. luteus vs. Fabaceae and extra-Fabales plastomes revealed the loss of the plastid rpl22 gene, and its functional relocation to the nucleus was verified using lupine transcriptomic data. An investigation into the evolutionary rate of coding and non-coding sequences among legume plastomes resulted in the identification of remarkably variable regions. This study resulted in the discovery of a novel, major 36-kb inversion, specific to the Genistoids. Chloroplast mutational hotspots were also identified, which contain novel and potentially informative regions for molecular

  19. Information theory, evolutionary innovations and evolvability.

    Science.gov (United States)

    Wagner, Andreas

    2017-12-05

    How difficult is it to 'discover' an evolutionary adaptation or innovation? I here suggest that information theory, in combination with high-throughput DNA sequencing, can help answer this question by quantifying a new phenotype's information content. I apply this framework to compute the phenotypic information associated with novel gene regulation and with the ability to use novel carbon sources. The framework can also help quantify how DNA duplications affect evolvability, estimate the complexity of phenotypes and clarify the meaning of 'progress' in Darwinian evolution.This article is part of the themed issue 'Process and pattern in innovations from cells to societies'. © 2017 The Author(s).

  20. Adaptation of Escherichia coli to glucose promotes evolvability in lactose.

    Science.gov (United States)

    Phillips, Kelly N; Castillo, Gerardo; Wünsche, Andrea; Cooper, Tim F

    2016-02-01

    The selective history of a population can influence its subsequent evolution, an effect known as historical contingency. We previously observed that five of six replicate populations that were evolved in a glucose-limited environment for 2000 generations, then switched to lactose for 1000 generations, had higher fitness increases in lactose than populations started directly from the ancestor. To test if selection in glucose systematically increased lactose evolvability, we started 12 replay populations--six from a population subsample and six from a single randomly selected clone--from each of the six glucose-evolved founder populations. These replay populations and 18 ancestral populations were evolved for 1000 generations in a lactose-limited environment. We found that replay populations were initially slightly less fit in lactose than the ancestor, but were more evolvable, in that they increased in fitness at a faster rate and to higher levels. This result indicates that evolution in the glucose environment resulted in genetic changes that increased the potential of genotypes to adapt to lactose. Genome sequencing identified four genes--iclR, nadR, spoT, and rbs--that were mutated in most glucose-evolved clones and are candidates for mediating increased evolvability. Our results demonstrate that short-term selective costs during selection in one environment can lead to changes in evolvability that confer longer term benefits. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  1. Evolvability of Amyloidogenic Proteins in Human Brain

    Science.gov (United States)

    Hashimoto, Makoto; Ho, Gilbert; Sugama, Shuei; Takamatsu, Yoshiki; Shimizu, Yuka; Takenouchi, Takato; Waragai, Masaaki; Masliah, Eliezer

    2018-01-01

     Currently, the physiological roles of amyloidogenic proteins (APs) in human brain, such as amyloid-β and α-synuclein, are elusive. Given that many APs arose by gene duplication and have been resistant against the pressures of natural selection, APs may be associated with some functions that are advantageous for survival of offspring. Nonetheless, evolvability is the sole physiological quality of APs that has been characterized in microorganisms such as yeast. Since yeast and human brain may share similar strategies in coping with diverse range of critical environmental stresses, the objective of this paper was to discuss the potential role of evolvability of APs in aging-associated neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. Given the heterogeneity of APs in terms of structure and cytotoxicity, it is argued that APs might be involved in preconditioning against diverse stresses in human brain. It is further speculated that these stress-related APs, most likely protofibrillar forms, might be transmitted to offspring via the germline, conferring preconditioning against forthcoming stresses. Thus, APs might represent a vehicle for the inheritance of the acquired characteristics against environmental stresses. Curiously, such a characteristic of APs is reminiscent of Charles Darwin’s ‘gemmules’, imagined molecules of heritability described in his pangenesis theory. We propose that evolvability might be a physiological function of APs during the reproductive stage and neurodegenerative diseases could be a by-product effect manifested later in aging. Collectively, our evolvability hypothesis may play a complementary role in the pathophysiology of APs with the conventional amyloid cascade hypothesis. PMID:29439348

  2. Evolutionary dynamics of gene and isoform regulation in Mammalian tissues.

    Science.gov (United States)

    Merkin, Jason; Russell, Caitlin; Chen, Ping; Burge, Christopher B

    2012-12-21

    Most mammalian genes produce multiple distinct messenger RNAs through alternative splicing, but the extent of splicing conservation is not clear. To assess tissue-specific transcriptome variation across mammals, we sequenced complementary DNA from nine tissues from four mammals and one bird in biological triplicate, at unprecedented depth. We find that while tissue-specific gene expression programs are largely conserved, alternative splicing is well conserved in only a subset of tissues and is frequently lineage-specific. Thousands of previously unknown, lineage-specific, and conserved alternative exons were identified; widely conserved alternative exons had signatures of binding by MBNL, PTB, RBFOX, STAR, and TIA family splicing factors, implicating them as ancestral mammalian splicing regulators. Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling.

  3. Platypus globin genes and flanking loci suggest a new insertional model for beta-globin evolution in birds and mammals

    Directory of Open Access Journals (Sweden)

    Warren Wesley C

    2008-07-01

    Full Text Available Abstract Background Vertebrate alpha (α- and beta (β-globin gene families exemplify the way in which genomes evolve to produce functional complexity. From tandem duplication of a single globin locus, the α- and β-globin clusters expanded, and then were separated onto different chromosomes. The previous finding of a fossil β-globin gene (ω in the marsupial α-cluster, however, suggested that duplication of the α-β cluster onto two chromosomes, followed by lineage-specific gene loss and duplication, produced paralogous α- and β-globin clusters in birds and mammals. Here we analyse genomic data from an egg-laying monotreme mammal, the platypus (Ornithorhynchus anatinus, to explore haemoglobin evolution at the stem of the mammalian radiation. Results The platypus α-globin cluster (chromosome 21 contains embryonic and adult α- globin genes, a β-like ω-globin gene, and the GBY globin gene with homology to cytoglobin, arranged as 5'-ζ-ζ'-αD-α3-α2-α1-ω-GBY-3'. The platypus β-globin cluster (chromosome 2 contains single embryonic and adult globin genes arranged as 5'-ε-β-3'. Surprisingly, all of these globin genes were expressed in some adult tissues. Comparison of flanking sequences revealed that all jawed vertebrate α-globin clusters are flanked by MPG-C16orf35 and LUC7L, whereas all bird and mammal β-globin clusters are embedded in olfactory genes. Thus, the mammalian α- and β-globin clusters are orthologous to the bird α- and β-globin clusters respectively. Conclusion We propose that α- and β-globin clusters evolved from an ancient MPG-C16orf35-α-β-GBY-LUC7L arrangement 410 million years ago. A copy of the original β (represented by ω in marsupials and monotremes was inserted into an array of olfactory genes before the amniote radiation (>315 million years ago, then duplicated and diverged to form orthologous clusters of β-globin genes with different expression profiles in different lineages.

  4. The Evolving Resource Metadata Infrastructure

    Science.gov (United States)

    Biemesderfer, Chris

    The search and discovery mechanisms that will facilitate and simplify systematic research on the Internet depend on systematic classifications of resources, as well as on standardized access to such metadata. The principles and technologies that will make this possible are evolving in the work of the Internet Engineering Task Force and the digital library initiatives, among others. The desired outcome is a set of standards, tools, and practices that permits both cataloging and retrieval to be comprehensive and efficient.

  5. Ranking in evolving complex networks

    Science.gov (United States)

    Liao, Hao; Mariani, Manuel Sebastian; Medo, Matúš; Zhang, Yi-Cheng; Zhou, Ming-Yang

    2017-05-01

    Complex networks have emerged as a simple yet powerful framework to represent and analyze a wide range of complex systems. The problem of ranking the nodes and the edges in complex networks is critical for a broad range of real-world problems because it affects how we access online information and products, how success and talent are evaluated in human activities, and how scarce resources are allocated by companies and policymakers, among others. This calls for a deep understanding of how existing ranking algorithms perform, and which are their possible biases that may impair their effectiveness. Many popular ranking algorithms (such as Google's PageRank) are static in nature and, as a consequence, they exhibit important shortcomings when applied to real networks that rapidly evolve in time. At the same time, recent advances in the understanding and modeling of evolving networks have enabled the development of a wide and diverse range of ranking algorithms that take the temporal dimension into account. The aim of this review is to survey the existing ranking algorithms, both static and time-aware, and their applications to evolving networks. We emphasize both the impact of network evolution on well-established static algorithms and the benefits from including the temporal dimension for tasks such as prediction of network traffic, prediction of future links, and identification of significant nodes.

  6. Impact of gene family evolutionary histories on phylogenetic species tree inference by gene tree parsimony.

    Science.gov (United States)

    Shi, Tao

    2016-03-01

    Complicated history of gene duplication and loss brings challenge to molecular phylogenetic inference, especially in deep phylogenies. However, phylogenomic approaches, such as gene tree parsimony (GTP), show advantage over some other approaches in its ability to use gene families with duplications. GTP searches the 'optimal' species tree by minimizing the total cost of biological events such as duplications, but accuracy of GTP and phylogenetic signal in the context of different gene families with distinct histories of duplication and loss are unclear. To evaluate how different evolutionary properties of different gene families can impact on species tree inference, 3900 gene families from seven angiosperms encompassing a wide range of gene content, lineage-specific expansions and contractions were analyzed. It was found that the gene content and total duplication number in a gene family strongly influence species tree inference accuracy, with the highest accuracy achieved at either very low or very high gene content (or duplication number) and lowest accuracy centered in intermediate gene content (or duplication number), as the relationship can fit a binomial regression. Besides, for gene families of similar level of average gene content, those with relatively higher lineage-specific expansion or duplication rates tend to show lower accuracy. Additional correlation tests support that high accuracy for those gene families with large gene content may rely on abundant ancestral copies to provide many subtrees to resolve conflicts, whereas high accuracy for single or low copy gene families are just subject to sequence substitution per se. Very low accuracy reached by gene families of intermediate gene content or duplication number can be due to insufficient subtrees to resolve the conflicts from loss of alternative copies. As these evolutionary properties can significantly influence species tree accuracy, I discussed the potential weighting of the duplication cost by

  7. The mammalian PYHIN gene family: Phylogeny, evolution and expression

    Directory of Open Access Journals (Sweden)

    Cridland Jasmyn A

    2012-08-01

    Full Text Available Abstract Background Proteins of the mammalian PYHIN (IFI200/HIN-200 family are involved in defence against infection through recognition of foreign DNA. The family member absent in melanoma 2 (AIM2 binds cytosolic DNA via its HIN domain and initiates inflammasome formation via its pyrin domain. AIM2 lies within a cluster of related genes, many of which are uncharacterised in mouse. To better understand the evolution, orthology and function of these genes, we have documented the range of PYHIN genes present in representative mammalian species, and undertaken phylogenetic and expression analyses. Results No PYHIN genes are evident in non-mammals or monotremes, with a single member found in each of three marsupial genomes. Placental mammals show variable family expansions, from one gene in cow to four in human and 14 in mouse. A single HIN domain appears to have evolved in the common ancestor of marsupials and placental mammals, and duplicated to give rise to three distinct forms (HIN-A, -B and -C in the placental mammal ancestor. Phylogenetic analyses showed that AIM2 HIN-C and pyrin domains clearly diverge from the rest of the family, and it is the only PYHIN protein with orthology across many species. Interestingly, although AIM2 is important in defence against some bacteria and viruses in mice, AIM2 is a pseudogene in cow, sheep, llama, dolphin, dog and elephant. The other 13 mouse genes have arisen by duplication and rearrangement within the lineage, which has allowed some diversification in expression patterns. Conclusions The role of AIM2 in forming the inflammasome is relatively well understood, but molecular interactions of other PYHIN proteins involved in defence against foreign DNA remain to be defined. The non-AIM2 PYHIN protein sequences are very distinct from AIM2, suggesting they vary in effector mechanism in response to foreign DNA, and may bind different DNA structures. The PYHIN family has highly varied gene composition between

  8. Molecular cloning, sequencing and tissue expression of vasotocin and isotocin precursor genes from Ostariophysian catfishes: Phylogeny and evolutionary considerations in teleosts

    Directory of Open Access Journals (Sweden)

    Putul eBanerjee

    2015-05-01

    Full Text Available Basic and neutral neurohypophyseal (NH nonapeptides have evolved from vasotocin (VT by a gene duplication at the base of the gnathostome lineage. In teleosts, VT and IT are the basic and neutral peptides, respectively. In the present study, VT and IT precursor genes of Heteropneustes fossilis and Clarias batrachus (Siluriformes, Ostariophysi were cloned and sequenced. The channel catfish Icatalurus punctatus NH precursor sequences were obtained from EST database. The catfish NH sequences were used along with the available Acanthopterygii and other vertebrate NH precursor sequences to draw phylogenetic inference on the evolutionary history of the teleost NH peptides. Synteny analysis of the NH gene loci in various teleost species was done to complement the phylogenetic analysis. In H. fossilis, the NH transcripts were also sequenced from the ovary. The cloned genes and the deduced precursor proteins showed conserved characteristics of the NH nonapeptide precursors. The genes are expressed in brain and ovary (follicular envelope of H. fossilis with higher transcript abundance in the brain. The addition of the catfish sequences in the phylogenetic analysis revealed that the VT and IT precursors of the species-rich superorders of teleosts have a distinct phylogenetic history with the Acanthopterygii VT and IT precursors sharing a less evolutionary distance and the Ostariophysi VT and IT having a greater evolutionary distance. The genomic location of VT and IT precursors, and synteny analysis of the NH loci lend support to the phylogenetic inference and suggest a footprint of fish- specific whole genome duplication (3R and subsequent diploidization in the NH loci. The VT and IT precursor genes are most likely lineage-specific paralogs resulting from differential losses of the 3R NH paralogs in the two superorders. The independent yet consistent retention of VT and IT in the two superorders might be directed by a stringent ligand-receptor selectivity.

  9. The evolvability of programmable hardware

    Science.gov (United States)

    Raman, Karthik; Wagner, Andreas

    2011-01-01

    In biological systems, individual phenotypes are typically adopted by multiple genotypes. Examples include protein structure phenotypes, where each structure can be adopted by a myriad individual amino acid sequence genotypes. These genotypes form vast connected ‘neutral networks’ in genotype space. The size of such neutral networks endows biological systems not only with robustness to genetic change, but also with the ability to evolve a vast number of novel phenotypes that occur near any one neutral network. Whether technological systems can be designed to have similar properties is poorly understood. Here we ask this question for a class of programmable electronic circuits that compute digital logic functions. The functional flexibility of such circuits is important in many applications, including applications of evolutionary principles to circuit design. The functions they compute are at the heart of all digital computation. We explore a vast space of 1045 logic circuits (‘genotypes’) and 1019 logic functions (‘phenotypes’). We demonstrate that circuits that compute the same logic function are connected in large neutral networks that span circuit space. Their robustness or fault-tolerance varies very widely. The vicinity of each neutral network contains circuits with a broad range of novel functions. Two circuits computing different functions can usually be converted into one another via few changes in their architecture. These observations show that properties important for the evolvability of biological systems exist in a commercially important class of electronic circuitry. They also point to generic ways to generate fault-tolerant, adaptable and evolvable electronic circuitry. PMID:20534598

  10. The 'E' factor -- evolving endodontics.

    Science.gov (United States)

    Hunter, M J

    2013-03-01

    Endodontics is a constantly developing field, with new instruments, preparation techniques and sealants competing with trusted and traditional approaches to tooth restoration. Thus general dental practitioners must question and understand the significance of these developments before adopting new practices. In view of this, the aim of this article, and the associated presentation at the 2013 British Dental Conference & Exhibition, is to provide an overview of endodontic methods and constantly evolving best practice. The presentation will review current preparation techniques, comparing rotary versus reciprocation, and question current trends in restoration of the endodontically treated tooth.

  11. Primordial evolvability: Impasses and challenges.

    Science.gov (United States)

    Vasas, Vera; Fernando, Chrisantha; Szilágyi, András; Zachár, István; Santos, Mauro; Szathmáry, Eörs

    2015-09-21

    While it is generally agreed that some kind of replicating non-living compounds were the precursors of life, there is much debate over their possible chemical nature. Metabolism-first approaches propose that mutually catalytic sets of simple organic molecules could be capable of self-replication and rudimentary chemical evolution. In particular, the graded autocatalysis replication domain (GARD) model, depicting assemblies of amphiphilic molecules, has received considerable interest. The system propagates compositional information across generations and is suggested to be a target of natural selection. However, evolutionary simulations indicate that the system lacks selectability (i.e. selection has negligible effect on the equilibrium concentrations). We elaborate on the lessons learnt from the example of the GARD model and, more widely, on the issue of evolvability, and discuss the implications for similar metabolism-first scenarios. We found that simple incorporation-type chemistry based on non-covalent bonds, as assumed in GARD, is unlikely to result in alternative autocatalytic cycles when catalytic interactions are randomly distributed. An even more serious problem stems from the lognormal distribution of catalytic factors, causing inherent kinetic instability of such loops, due to the dominance of efficiently catalyzed components that fail to return catalytic aid. Accordingly, the dynamics of the GARD model is dominated by strongly catalytic, but not auto-catalytic, molecules. Without effective autocatalysis, stable hereditary propagation is not possible. Many repetitions and different scaling of the model come to no rescue. Despite all attempts to show the contrary, the GARD model is not evolvable, in contrast to reflexively autocatalytic networks, complemented by rare uncatalyzed reactions and compartmentation. The latter networks, resting on the creation and breakage of chemical bonds, can generate novel ('mutant') autocatalytic loops from a given set of

  12. Peripartum hysterectomy: an evolving picture.

    LENUS (Irish Health Repository)

    Turner, Michael J

    2012-02-01

    Peripartum hysterectomy (PH) is one of the obstetric catastrophes. Evidence is emerging that the role of PH in modern obstetrics is evolving. Improving management of postpartum hemorrhage and newer surgical techniques should decrease PH for uterine atony. Rising levels of repeat elective cesarean deliveries should decrease PH following uterine scar rupture in labor. Increasing cesarean rates, however, have led to an increase in the number of PHs for morbidly adherent placenta. In the case of uterine atony or rupture where PH is required, a subtotal PH is often sufficient. In the case of pathological placental localization involving the cervix, however, a total hysterectomy is required. Furthermore, the involvement of other pelvic structures may prospectively make the diagnosis difficult and the surgery challenging. If resources permit, PH for pathological placental localization merits a multidisciplinary approach. Despite advances in clinical practice, it is likely that peripartum hysterectomy will be more challenging for obstetricians in the future.

  13. Extreme evolved solar systems (EESS)

    Science.gov (United States)

    Gaensicke, Boris

    2017-08-01

    In just 20 years, we went from not knowing if the solar system is a fluke of Nature to realising that it is totally normal for stars to have planets. More remarkably, it is now clear that planet formation is a robust process, as rich multi-planet systems are found around stars more massive and less massive than the Sun. More recently, planetary systems have been identified in increasingly complex architectures, including circumbinary planets, wide binaries with planets orbiting one or both stellar components, and planets in triple stellar systems.We have also learned that many planetary systems will survive the evolution of their host stars into the white dwarf phase. Small bodies are scattered by unseen planets into the gravitational field of the white dwarfs, tidally disrupt, form dust discs, and eventually accrete onto the white dwarf, where they can be spectroscopically detected. HST/COS has played a critical role in the study these evolved planetary systems, demonstrating that overall the bulk composition of the debris is rocky and resembles in composition the inner the solar system, including evidence for water-rich planetesimals. Past observations of planetary systems at white dwarfs have focused on single stars with main-sequence progenitors of 1.5 to 2.5Msun. Here we propose to take the study of evolved planetary systems into the extremes of parameter ranges to answer questions such as: * How efficient is planet formation around 4-10Msun stars? * What are the metallicities of the progenitors of debris-accreting white dwarfs?* What is the fate of circumbinary planets?* Can star-planet interactions generate magnetic fields in the white dwarf host?

  14. Epigenetic regulation of gene expression in porcine epiblast, hypoblast, trophectoderm and epiblast-derived neural progenitor cells

    DEFF Research Database (Denmark)

    Gao, Yu; Jammes, Helen; Rasmussen, Mikkel Aabech

    2011-01-01

    After fertilization, lineage specification is governed by a complicated molecular network in which permissiveness and repression of expression of pluripotency- and differentiation-associated genes are regulated by epigenetic modifications. DNA methylation operates as a very stable repressive mark...... of its promoter. In conclusion, DNA methylation is an inconsistently operating epigenetic mechanism in porcine E10 blastocysts, whereas in porcine epiblast-derived NPCs, expression of pluripotency-associated and differentiation genes appear to be regulated by this modification.......After fertilization, lineage specification is governed by a complicated molecular network in which permissiveness and repression of expression of pluripotency- and differentiation-associated genes are regulated by epigenetic modifications. DNA methylation operates as a very stable repressive mark...

  15. Gene

    Data.gov (United States)

    U.S. Department of Health & Human Services — Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes,...

  16. Evolving strategies for cancer and autoimmunity: back to the future

    Directory of Open Access Journals (Sweden)

    Peter John Lane

    2014-04-01

    Full Text Available Although current thinking has focused on genetic variation between individuals and environmental influences as underpinning susceptibility to both autoimmunity and cancer, an alternative view is that human susceptibility to these diseases is a consequence of the way the immune system evolved. It is important to remember that the immunological genes that we inherit and the systems that they control were shaped by the drive for reproductive success rather than for individual survival. It is our view that human susceptibility to autoimmunity and cancer are the evolutionarily acceptable side effects of the immune adaptations that evolved in early placental mammals to accommodate a fundamental change in reproductive strategy. Studies of immune function in mammals shows that high affinity antibodies and CD4 memory, along with its regulation, co-evolved with placentation. By dissection of the immunologically active genes and proteins that evolved to regulate this step change in the mammalian immune system, clues have emerged that may reveal ways of detuning both effector and regulatory arms of the immune system to abrogate autoimmune responses whilst preserving protection against infection. Paradoxically, it appears that such a detuned and deregulated immune system is much better equipped to mount anti-tumor immune responses against cancers.

  17. CERN internal communication is evolving

    CERN Multimedia

    2016-01-01

    CERN news will now be regularly updated on the CERN People page (see here).      Dear readers, All over the world, communication is becoming increasingly instantaneous, with news published in real time on websites and social networks. In order to keep pace with these changes, CERN's internal communication is evolving too. From now on, you will be informed of what’s happening at CERN more often via the “CERN people” page, which will frequently be updated with news. The Bulletin is following this trend too: twice a month, we will compile the most important articles published on the CERN site, with a brand-new layout. You will receive an e-mail every two weeks as soon as this new form of the Bulletin is available. If you have interesting news or stories to share, tell us about them through the form at: https://communications.web.cern.ch/got-story-cern-website​. You can also find out about news from CERN in real time...

  18. Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα.

    Science.gov (United States)

    Dijkstra, Johannes M; Takizawa, Fumio; Fischer, Uwe; Friedrich, Maik; Soto-Lampe, Veronica; Lefèvre, Christophe; Lenk, Matthias; Karger, Axel; Matsui, Taei; Hashimoto, Keiichiro

    2014-02-01

    Interleukins 2 and 15 (IL-2 and IL-15) are highly differentiated but related cytokines with overlapping, yet also distinct functions, and established benefits for medical drug use. The present study identified a gene for an ancient third IL-2/15 family member in reptiles and mammals, interleukin 15-like (IL-15L), which hitherto was only reported in fish. IL-15L genes with intact open reading frames (ORFs) and evidence of transcription, and a recent past of purifying selection, were found for cattle, horse, sheep, pig and rabbit. In human and mouse the IL-15L ORF is incapacitated. Although deduced IL-15L proteins share only ~21 % overall amino acid identity with IL-15, they share many of the IL-15 residues important for binding to receptor chain IL-15Rα, and recombinant bovine IL-15L was shown to interact with IL-15Rα indeed. Comparison of sequence motifs indicates that capacity for binding IL-15Rα is an ancestral characteristic of the IL-2/15/15L family, in accordance with a recent study which showed that in fish both IL-2 and IL-15 can bind IL-15Rα. Evidence reveals that the species lineage leading to mammals started out with three similar cytokines IL-2, IL-15 and IL-15L, and that later in evolution (1) IL-2 and IL-2Rα receptor chain acquired a new and specific binding mode and (2) IL-15L was lost in several but not all groups of mammals. The present study forms an important step forward in understanding this potent family of cytokines, and may help to improve future strategies for their application in veterinarian and human medicine.

  19. On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks

    National Research Council Canada - National Science Library

    Tonelli, Paul; Mouret, Jean-Baptiste

    2013-01-01

    .... It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks...

  20. 5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells.

    Directory of Open Access Journals (Sweden)

    Krzysztof Poterlowicz

    2017-09-01

    Full Text Available Mammalian genomes contain several dozens of large (>0.5 Mbp lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene

  1. 5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells.

    Science.gov (United States)

    Poterlowicz, Krzysztof; Yarker, Joanne L; Malashchuk, Igor; Lajoie, Brian R; Mardaryev, Andrei N; Gdula, Michal R; Sharov, Andrey A; Kohwi-Shigematsu, Terumi; Botchkarev, Vladimir A; Fessing, Michael Y

    2017-09-01

    Mammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and

  2. DNA evolved to minimize frameshift mutations

    OpenAIRE

    Agoni, Valentina

    2013-01-01

    Point mutations can surely be dangerous but what is worst than to lose the reading frame?! Does DNA evolved a strategy to try to limit frameshift mutations?! Here we investigate if DNA sequences effectively evolved a system to minimize frameshift mutations analyzing the transcripts of proteins with high molecular weights.

  3. Gene Expression Data from the Moon Jelly, Aurelia, Provide Insights into the Evolution of the Combinatorial Code Controlling Animal Sense Organ Development.

    Science.gov (United States)

    Nakanishi, Nagayasu; Camara, Anthony C; Yuan, David C; Gold, David A; Jacobs, David K

    2015-01-01

    In Bilateria, Pax6, Six, Eya and Dach families of transcription factors underlie the development and evolution of morphologically and phyletically distinct eyes, including the compound eyes in Drosophila and the camera-type eyes in vertebrates, indicating that bilaterian eyes evolved under the strong influence of ancestral developmental gene regulation. However the conservation in eye developmental genetics deeper in the Eumetazoa, and the origin of the conserved gene regulatory apparatus controlling eye development remain unclear due to limited comparative developmental data from Cnidaria. Here we show in the eye-bearing scyphozoan cnidarian Aurelia that the ectodermal photosensory domain of the developing medusa sensory structure known as the rhopalium expresses sine oculis (so)/six1/2 and eyes absent/eya, but not optix/six3/6 or pax (A&B). In addition, the so and eya co-expression domain encompasses the region of active cell proliferation, neurogenesis, and mechanoreceptor development in rhopalia. Consistent with the role of so and eya in rhopalial development, developmental transcriptome data across Aurelia life cycle stages show upregulation of so and eya, but not optix or pax (A&B), during medusa formation. Moreover, pax6 and dach are absent in the Aurelia genome, and thus are not required for eye development in Aurelia. Our data are consistent with so and eya, but not optix, pax or dach, having conserved functions in sensory structure specification across Eumetazoa. The lability of developmental components including Pax genes relative to so-eya is consistent with a model of sense organ development and evolution that involved the lineage specific modification of a combinatorial code that specifies animal sense organs.

  4. Gene Expression Data from the Moon Jelly, Aurelia, Provide Insights into the Evolution of the Combinatorial Code Controlling Animal Sense Organ Development.

    Directory of Open Access Journals (Sweden)

    Nagayasu Nakanishi

    Full Text Available In Bilateria, Pax6, Six, Eya and Dach families of transcription factors underlie the development and evolution of morphologically and phyletically distinct eyes, including the compound eyes in Drosophila and the camera-type eyes in vertebrates, indicating that bilaterian eyes evolved under the strong influence of ancestral developmental gene regulation. However the conservation in eye developmental genetics deeper in the Eumetazoa, and the origin of the conserved gene regulatory apparatus controlling eye development remain unclear due to limited comparative developmental data from Cnidaria. Here we show in the eye-bearing scyphozoan cnidarian Aurelia that the ectodermal photosensory domain of the developing medusa sensory structure known as the rhopalium expresses sine oculis (so/six1/2 and eyes absent/eya, but not optix/six3/6 or pax (A&B. In addition, the so and eya co-expression domain encompasses the region of active cell proliferation, neurogenesis, and mechanoreceptor development in rhopalia. Consistent with the role of so and eya in rhopalial development, developmental transcriptome data across Aurelia life cycle stages show upregulation of so and eya, but not optix or pax (A&B, during medusa formation. Moreover, pax6 and dach are absent in the Aurelia genome, and thus are not required for eye development in Aurelia. Our data are consistent with so and eya, but not optix, pax or dach, having conserved functions in sensory structure specification across Eumetazoa. The lability of developmental components including Pax genes relative to so-eya is consistent with a model of sense organ development and evolution that involved the lineage specific modification of a combinatorial code that specifies animal sense organs.

  5. High diversity of polyketide synthase genes and the melanin biosynthesis gene cluster in Penicillium marneffei.

    Science.gov (United States)

    Woo, Patrick C Y; Tam, Emily W T; Chong, Ken T K; Cai, James J; Tung, Edward T K; Ngan, Antonio H Y; Lau, Susanna K P; Yuen, Kwok-Yung

    2010-09-01

    Despite the unique phenotypic properties and clinical importance of Penicillium marneffei, the polyketide synthase genes in its genome have never been characterized. Twenty-three putative polyketide synthase genes and two putative polyketide synthase nonribosomal peptide-synthase hybrid genes were identified in the P. marneffei genome, a diversity much higher than found in other pathogenic thermal dimorphic fungi, such as Histoplasma capsulatum (one polyketide synthase gene) and Coccidioides immitis (10 polyketide synthase genes). These genes were evenly distributed on the phylogenetic tree with polyketide synthase genes of Aspergillus and other fungi, indicating that the high diversity was not a result of lineage-specific gene expansion through recent gene duplication. The melanin-biosynthesis gene cluster had gene order and orientations identical to those in the Talaromyces stipitatus (a teleomorph of Penicillium emmonsii) genome. Phylogenetically, all six genes of the melanin-biosynthesis gene cluster in P. marneffei were also most closely related to those in T. stipitatus, with high bootstrap supports. The polyketide synthase gene of the melanin-biosynthesis gene cluster (alb1) in P. marneffei was knocked down, which was accompanied by loss of melanin pigment production and reduced ornamentation in conidia. The survival of mice challenged with the alb1 knockdown mutant was significantly better than those challenged with wild-type P. marneffei (P melanin-biosynthesis gene cluster contributed to virulence through decreased susceptibility to killing by hydrogen peroxide. © 2010 The Authors Journal compilation © 2010 FEBS.

  6. Survival of the fastest: Evolving wings for flapping flight

    Science.gov (United States)

    Ramananarivo, Sophie; Mitchel, Thomas; Ristroph, Leif

    2014-11-01

    To optimize flapping flight with regard to wing shape, we use an evolutionary or genetic algorithm to improve the forward speed of 3d-printed wings or hydrofoils that heave up-and-down and self-propel within water. In this scheme, ``genes'' are mathematical parameters specifying wing shape, and ``breeding'' involves the merging and mutation of genes from two parent wings to form a child. A wing's swimming speed is its ``fitness'', which dictates the likelihood of breeding and thus passing on its genes to the next generation. We find that this iterative process leads to marked improvements in relatively few generations, and several distinct shape features are shared among the fastest wings. We also investigate the favorable flow structures produced by these elite swimmers and compare their shape and performance to biologically evolved wings, fins, tails, and flippers.

  7. Insect sex determination: it all evolves around transformer.

    Science.gov (United States)

    Verhulst, Eveline C; van de Zande, Louis; Beukeboom, Leo W

    2010-08-01

    Insects exhibit a variety of sex determining mechanisms including male or female heterogamety and haplodiploidy. The primary signal that starts sex determination is processed by a cascade of genes ending with the conserved switch doublesex that controls sexual differentiation. Transformer is the doublesex splicing regulator and has been found in all examined insects, indicating its ancestral function as a sex-determining gene. Despite this conserved function, the variation in transformer nucleotide sequence, amino acid composition and protein structure can accommodate a multitude of upstream sex determining signals. Transformer regulation of doublesex and its taxonomic distribution indicate that the doublesex-transformer axis is conserved among all insects and that transformer is the key gene around which variation in sex determining mechanisms has evolved.

  8. WSC-07: Evolving the Web Services Challenge

    NARCIS (Netherlands)

    Blake, M. Brian; Cheung, William K.W.; Jaeger, Michael C.; Wombacher, Andreas

    Service-oriented architecture (SOA) is an evolving architectural paradigm where businesses can expose their capabilities as modular, network-accessible software services. By decomposing capabilities into modular services, organizations can share their offerings at multiple levels of granularity

  9. Satcom access in the evolved packet core

    NARCIS (Netherlands)

    Cano, M.D.; Norp, A.H.J.; Popova, M.P.

    2012-01-01

    Satellite communications (Satcom) networks are increasingly integrating with terrestrial communications networks, namely Next Generation Networks (NGN). In the area of NGN the Evolved Packet Core (EPC) is a new network architecture that can support multiple access technologies. When Satcom is

  10. Acquisition: Acquisition of the Evolved SEASPARROW Missile

    National Research Council Canada - National Science Library

    2002-01-01

    .... The Evolved SEASPARROW Missile, a Navy Acquisition Category II program, is an improved version of the RIM-7P SEASPARROW missile that will intercept high-speed maneuvering, anti-ship cruise missiles...

  11. Cyberspace Operations: Influence Upon Evolving War Theory

    Science.gov (United States)

    2011-03-18

    St ra te gy R es ea rc h Pr oj ec t CYBERSPACE OPERATIONS: INFLUENCE UPON EVOLVING WAR THEORY BY COLONEL KRISTIN BAKER United States...DATES COVERED (From - To) 4. TITLE AND SUBTITLE Cyberspace Operations: Influence Upon Evolving War Theory 5a. CONTRACT NUMBER... Leadership 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S

  12. Evolving effective incremental SAT solvers with GP

    OpenAIRE

    Bader, Mohamed; Poli, R.

    2008-01-01

    Hyper-Heuristics could simply be defined as heuristics to choose other heuristics, and it is a way of combining existing heuristics to generate new ones. In a Hyper-Heuristic framework, the framework is used for evolving effective incremental (Inc*) solvers for SAT. We test the evolved heuristics (IncHH) against other known local search heuristics on a variety of benchmark SAT problems.

  13. Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

    DEFF Research Database (Denmark)

    Bailey, Susan; Hinz, Aaron; Kassen, Rees

    2014-01-01

    Conventional wisdom holds that synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have no detectable effect on phenotype or fitness. However, a growing body of evidence from both comparative and experimental studies suggests otherwise. Synonymous mutations have been...... in an experimentally evolved population of Pseudomonas fluorescens. We show experimentally that these mutations increase fitness by an amount comparable to non-synonymous mutations and that the fitness increases stem from increased gene expression. These results provide unequivocal evidence that synonymous mutations...... can drive adaptive evolution and suggest that this class of mutation may be underappreciated as a cause of adaptation and evolutionary dynamics....

  14. Evolvability Search: Directly Selecting for Evolvability in order to Study and Produce It

    DEFF Research Database (Denmark)

    Mengistu, Henok; Lehman, Joel Anthony; Clune, Jeff

    2016-01-01

    One hallmark of natural organisms is their significant evolvability, i.e.,their increased potential for further evolution. However, reproducing such evolvability in artificial evolution remains a challenge, which both reduces the performance of evolutionary algorithms and inhibits the study...... of evolvable digital phenotypes. Although some types of selection in evolutionary computation indirectly encourage evolvability, one unexplored possibility is to directly select for evolvability. To do so, we estimate an individual's future potential for diversity by calculating the behavioral diversity of its...... immediate offspring, and select organisms with increased offspring variation. While the technique is computationally expensive, we hypothesized that direct selection would better encourage evolvability than indirect methods. Experiments in two evolutionary robotics domains confirm this hypothesis: in both...

  15. Evolved atmospheric entry corridor with safety factor

    Science.gov (United States)

    Liang, Zixuan; Ren, Zhang; Li, Qingdong

    2018-02-01

    Atmospheric entry corridors are established in previous research based on the equilibrium glide condition which assumes the flight-path angle to be zero. To get a better understanding of the highly constrained entry flight, an evolved entry corridor that considers the exact flight-path angle is developed in this study. Firstly, the conventional corridor in the altitude vs. velocity plane is extended into a three-dimensional one in the space of altitude, velocity, and flight-path angle. The three-dimensional corridor is generated by a series of constraint boxes. Then, based on a simple mapping method, an evolved two-dimensional entry corridor with safety factor is obtained. The safety factor is defined to describe the flexibility of the flight-path angle for a state within the corridor. Finally, the evolved entry corridor is simulated for the Space Shuttle and the Common Aero Vehicle (CAV) to demonstrate the effectiveness of the corridor generation approach. Compared with the conventional corridor, the evolved corridor is much wider and provides additional information. Therefore, the evolved corridor would benefit more to the entry trajectory design and analysis.

  16. Interactively Evolving Compositional Sound Synthesis Networks

    DEFF Research Database (Denmark)

    Jónsson, Björn Þór; Hoover, Amy K.; Risi, Sebastian

    2015-01-01

    While the success of electronic music often relies on the uniqueness and quality of selected timbres, many musicians struggle with complicated and expensive equipment and techniques to create their desired sounds. Instead, this paper presents a technique for producing novel timbres that are evolved......, CPPNs can theoretically compute any function and can build on those present in traditional synthesizers (e.g. square, sawtooth, triangle, and sine waves functions) to produce completely novel timbres. Evolved with NeuroEvolution of Augmenting Topologies (NEAT), the aim of this paper is to explore...... the space of potential sounds that can be generated through such compositional sound synthesis networks (CSSNs). To study the effect of evolution on subjective appreciation, participants in a listener study ranked evolved timbres by personal preference, resulting in preferences skewed toward the first...

  17. How the first biopolymers could have evolved.

    Science.gov (United States)

    Abkevich, V I; Gutin, A M; Shakhnovich, E I

    1996-01-01

    In this work, we discuss a possible origin of the first biopolymers with stable unique structures. We suggest that at the prebiotic stage of evolution, long organic polymers had to be compact to avoid hydrolysis and had to be soluble and thus must not be exceedingly hydrophobic. We present an algorithm that generates such sequences for model proteins. The evolved sequences turn out to have a stable unique structure, into which they quickly fold. This result illustrates the idea that the unique three-dimensional native structures of first biopolymers could have evolved as a side effect of nonspecific physicochemical factors acting at the prebiotic stage of evolution. PMID:8570645

  18. Evolving Intelligent Systems Methodology and Applications

    CERN Document Server

    Angelov, Plamen; Kasabov, Nik

    2010-01-01

    From theory to techniques, the first all-in-one resource for EIS. There is a clear demand in advanced process industries, defense, and Internet and communication (VoIP) applications for intelligent yet adaptive/evolving systems. Evolving Intelligent Systems is the first self- contained volume that covers this newly established concept in its entirety, from a systematic methodology to case studies to industrial applications. Featuring chapters written by leading world experts, it addresses the progress, trends, and major achievements in this emerging research field, with a strong emphasis on th

  19. On the Relationships between Generative Encodings, Regularity, and Learning Abilities when Evolving Plastic Artificial Neural Networks: e79138

    National Research Council Canada - National Science Library

    Paul Tonelli; Jean-Baptiste Mouret

    2013-01-01

    .... It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks...

  20. Preface: evolving rotifers, evolving science: Proceedings of the XIV International Rotifer Symposium

    Czech Academy of Sciences Publication Activity Database

    Devetter, Miloslav; Fontaneto, D.; Jersabek, Ch.D.; Welch, D.B.M.; May, L.; Walsh, E.J.

    2017-01-01

    Roč. 796, č. 1 (2017), s. 1-6 ISSN 0018-8158 Institutional support: RVO:60077344 Keywords : evolving rotifers * 14th International Rotifer Symposium * evolving science Subject RIV: EG - Zoology OBOR OECD: Zoology Impact factor: 2.056, year: 2016

  1. Thermal and Evolved-Gas Analyzer Illustration

    Science.gov (United States)

    2008-01-01

    This is a computer-aided drawing of the Thermal and Evolved-Gas Analyzer, or TEGA, on NASA's Phoenix Mars Lander. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  2. Apollo 16 Evolved Lithology Sodic Ferrogabbro

    Science.gov (United States)

    Zeigler, Ryan; Jolliff, B. L.; Korotev, R. L.

    2014-01-01

    Evolved lunar igneous lithologies, often referred to as the alkali suite, are a minor but important component of the lunar crust. These evolved samples are incompatible-element rich samples, and are, not surprisingly, most common in the Apollo sites in (or near) the incompatible-element rich region of the Moon known as the Procellarum KREEP Terrane (PKT). The most commonly occurring lithologies are granites (A12, A14, A15, A17), monzogabbro (A14, A15), alkali anorthosites (A12, A14), and KREEP basalts (A15, A17). The Feldspathic Highlands Terrane is not entirely devoid of evolved lithologies, and rare clasts of alkali gabbronorite and sodic ferrogabbro (SFG) have been identified in Apollo 16 station 11 breccias 67915 and 67016. Curiously, nearly all pristine evolved lithologies have been found as small clasts or soil particles, exceptions being KREEP basalts 15382/6 and granitic sample 12013 (which is itself a breccia). Here we reexamine the petrography and geochemistry of two SFG-like particles found in a survey of Apollo 16 2-4 mm particles from the Cayley Plains 62283,7-15 and 62243,10-3 (hereafter 7-15 and 10-3 respectively). We will compare these to previously reported SFG samples, including recent analyses on the type specimen of SFG from lunar breccia 67915.

  3. Evolution of networks for body plan patterning; interplay of modularity, robustness and evolvability.

    Science.gov (United States)

    Ten Tusscher, Kirsten H; Hogeweg, Paulien

    2011-10-01

    A major goal of evolutionary developmental biology (evo-devo) is to understand how multicellular body plans of increasing complexity have evolved, and how the corresponding developmental programs are genetically encoded. It has been repeatedly argued that key to the evolution of increased body plan complexity is the modularity of the underlying developmental gene regulatory networks (GRNs). This modularity is considered essential for network robustness and evolvability. In our opinion, these ideas, appealing as they may sound, have not been sufficiently tested. Here we use computer simulations to study the evolution of GRNs' underlying body plan patterning. We select for body plan segmentation and differentiation, as these are considered to be major innovations in metazoan evolution. To allow modular networks to evolve, we independently select for segmentation and differentiation. We study both the occurrence and relation of robustness, evolvability and modularity of evolved networks. Interestingly, we observed two distinct evolutionary strategies to evolve a segmented, differentiated body plan. In the first strategy, first segments and then differentiation domains evolve (SF strategy). In the second scenario segments and domains evolve simultaneously (SS strategy). We demonstrate that under indirect selection for robustness the SF strategy becomes dominant. In addition, as a byproduct of this larger robustness, the SF strategy is also more evolvable. Finally, using a combined functional and architectural approach, we determine network modularity. We find that while SS networks generate segments and domains in an integrated manner, SF networks use largely independent modules to produce segments and domains. Surprisingly, we find that widely used, purely architectural methods for determining network modularity completely fail to establish this higher modularity of SF networks. Finally, we observe that, as a free side effect of evolving segmentation and

  4. Chromatin priming of genes in development: Concepts, mechanisms and consequences.

    Science.gov (United States)

    Bonifer, Constanze; Cockerill, Peter N

    2017-05-01

    During ontogeny, cells progress through multiple alternate differentiation states by activating distinct gene regulatory networks. In this review, we highlight the important role of chromatin priming in facilitating gene activation during lineage specification and in maintaining an epigenetic memory of previous gene activation. We show that chromatin priming is part of a hugely diverse repertoire of regulatory mechanisms that genes use to ensure that they are expressed at the correct time, in the correct cell type, and at the correct level, but also that they react to signals. We also emphasize how increasing our knowledge of these principles could inform our understanding of developmental failure and disease. Copyright © 2017 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  5. Histone variant innovation in a rapidly evolving chordate lineage

    Directory of Open Access Journals (Sweden)

    Jansen Pascal WTC

    2011-07-01

    Full Text Available Abstract Background Histone variants alter the composition of nucleosomes and play crucial roles in transcription, chromosome segregation, DNA repair, and sperm compaction. Modification of metazoan histone variant lineages occurs on a background of genome architecture that shows global similarities from sponges to vertebrates, but the urochordate, Oikopleura dioica, a member of the sister group to vertebrates, exhibits profound modification of this ancestral architecture. Results We show that a histone complement of 47 gene loci encodes 31 histone variants, grouped in distinct sets of developmental expression profiles throughout the life cycle. A particularly diverse array of 15 male-specific histone variants was uncovered, including a testes-specific H4t, the first metazoan H4 sequence variant reported. Universal histone variants H3.3, CenH3, and H2A.Z are present but O. dioica lacks homologs of macroH2A and H2AX. The genome encodes many H2A and H2B variants and the repertoire of H2A.Z isoforms is expanded through alternative splicing, incrementally regulating the number of acetylatable lysine residues in the functionally important N-terminal "charge patch". Mass spectrometry identified 40 acetylation, methylation and ubiquitylation posttranslational modifications (PTMs and showed that hallmark PTMs of "active" and "repressive" chromatin were present in O. dioica. No obvious reduction in silent heterochromatic marks was observed despite high gene density in this extraordinarily compacted chordate genome. Conclusions These results show that histone gene complements and their organization differ considerably even over modest phylogenetic distances. Substantial innovation among all core and linker histone variants has evolved in concert with adaptation of specific life history traits in this rapidly evolving chordate lineage.

  6. Evolving wormhole geometries within nonlinear electrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Arellano, Aaron V B [Facultad de Ciencias, Universidad Autonoma del Estado de Mexico, El Cerrillo, Piedras Blancas, CP 50200, Toluca (Mexico); Lobo, Francisco S N [Centro de Astronomia e Astrofisica da Universidade de Lisboa, Campo Grande, Ed C8 1749-016 Lisbon (Portugal)

    2006-10-21

    In this work, we explore the possibility of evolving (2 + 1) and (3 + 1)-dimensional wormhole spacetimes, conformally related to the respective static geometries, within the context of nonlinear electrodynamics. For (3 + 1)-dimensional spacetime, it is found that the Einstein field equation imposes a contracting wormhole solution and the obedience of the weak energy condition. Nevertheless, in the presence of an electric field, the latter presents a singularity at the throat; however, for a pure magnetic field the solution is regular. For (2 + 1)-dimensional case, it is also found that the physical fields are singular at the throat. Thus, taking into account the principle of finiteness, which states that a satisfactory theory should avoid physical quantities becoming infinite, one may rule out evolving (3 + 1)-dimensional wormhole solutions, in the presence of an electric field, and (2 + 1)-dimensional case coupled to nonlinear electrodynamics.

  7. Continual Learning through Evolvable Neural Turing Machines

    DEFF Research Database (Denmark)

    Lüders, Benno; Schläger, Mikkel; Risi, Sebastian

    2016-01-01

    Continual learning, i.e. the ability to sequentially learn tasks without catastrophic forgetting of previously learned ones, is an important open challenge in machine learning. In this paper we take a step in this direction by showing that the recently proposed Evolving Neural Turing Machine (ENT......) approach is able to perform one-shot learning in a reinforcement learning task without catastrophic forgetting of previously stored associations.......Continual learning, i.e. the ability to sequentially learn tasks without catastrophic forgetting of previously learned ones, is an important open challenge in machine learning. In this paper we take a step in this direction by showing that the recently proposed Evolving Neural Turing Machine (ENTM...

  8. Designing Garments to Evolve Over Time

    DEFF Research Database (Denmark)

    Riisberg, Vibeke; Grose, Lynda

    2017-01-01

    This paper proposes a REDO of the current fashion paradigm by investigating how garments might be designed to evolve over time. The purpose is to discuss ways of expanding the traditional role of the designer to include temporal dimensions of creating, producing and using clothes and to suggest a...... to a REDO of design education, to further research and the future fashion and textile industry.......This paper proposes a REDO of the current fashion paradigm by investigating how garments might be designed to evolve over time. The purpose is to discuss ways of expanding the traditional role of the designer to include temporal dimensions of creating, producing and using clothes and to suggest...... a range of potential fashion futures that decouple from declining resources. In the first part literature on 'Past and Present' historical and current aspects of sustainability in fashion and textiles are presented. In the second part, three exploratory case studies are described: Two projects by students...

  9. Antibody therapeutics - the evolving patent landscape.

    Science.gov (United States)

    Petering, Jenny; McManamny, Patrick; Honeyman, Jane

    2011-09-01

    The antibody patent landscape has evolved dramatically over the past 30 years, particularly in areas of technology relating to antibody modification to reduce immunogenicity in humans or improve antibody function. In some cases antibody techniques that were developed in the 1980s are still the subject of patent protection in the United States or Canada. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. The evolving epidemiology of inflammatory bowel disease.

    LENUS (Irish Health Repository)

    Shanahan, Fergus

    2009-07-01

    Epidemiologic studies in inflammatory bowel disease (IBD) include assessments of disease burden and evolving patterns of disease presentation. Although it is hoped that sound epidemiologic studies provide aetiological clues, traditional risk factor-based epidemiology has provided limited insights into either Crohn\\'s disease or ulcerative colitis etiopathogenesis. In this update, we will summarize how the changing epidemiology of IBD associated with modernization can be reconciled with current concepts of disease mechanisms and will discuss studies of clinically significant comorbidity in IBD.

  11. Directional Communication in Evolved Multiagent Teams

    Science.gov (United States)

    2013-06-10

    networks. Artificial Life, 15(2):185– 212, 2009. [23] K. O. Stanley and R. Miikkulainen. Evolving neural networks through augmenting topologies ...paper. 2.2 Neuroevolution of Augmenting Topologies The HyperNEAT approach is itself an extension of the original NEAT (Neu- roevolution of Augmenting ...Gauci and K. O. Stanley. Autonomous evolution of topographic regu- larities in artificial neural networks. Neural Computation, 22(7):1860–1898, 2010

  12. The Evolving Leadership Path of Visual Analytics

    Energy Technology Data Exchange (ETDEWEB)

    Kluse, Michael; Peurrung, Anthony J.; Gracio, Deborah K.

    2012-01-02

    This is a requested book chapter for an internationally authored book on visual analytics and related fields, coordianted by a UK university and to be published by Springer in 2012. This chapter is an overview of the leadship strategies that PNNL's Jim Thomas and other stakeholders used to establish visual analytics as a field, and how those strategies may evolve in the future.

  13. Raeder paratrigeminal neuralgia evolving to hemicrania continua.

    Science.gov (United States)

    Porzukowiak, Tina Renae

    2015-04-01

    Raeder paratrigeminal neuralgia is most commonly characterized as deep, boring, nonpulsatile, severe, unilateral facial and head pain in the distribution of the V1 area combined with ipsilateral oculosympathetic palsy and autonomic symptoms. Raeder paratrigeminal neuralgia evolving into hemicrania continua, a rare primary, chronic headache syndrome characterized by unilateral pain and response to indomethacin, has rarely been documented. The purpose of this case report is to contribute to the medical literature a single case of Raeder paratrigeminal neuralgia presenting as multiple cranial nerve palsies that evolved into hemicrania continua that was successfully treated with onabotulinumtoxinA. A 52-year-old white woman presented to the emergency department with the complaint of severe, aching, constant eye pain radiating to the V1 area for 1 week with associated ptosis and photophobia of the left eye. Ocular examination revealed involvement of cranial nerves II, III, V, and VI. Additional symptoms included ipsilateral lacrimation, eyelid edema, and rhinorrhea. Extensive medical work-up showed normal results. Raeder paratrigeminal neuralgia was diagnosed with multiple cranial nerve involvement; the headache component became chronic with periodic exacerbations of autonomic symptoms evolving to a diagnosis of hemicrania continua. The patient was intolerant to traditional indomethacin treatment, and the headache was successfully treated with onabotulinumtoxinA injections. Recognition of ipsilateral signs such as miosis, ptosis, hydrosis, eyelid edema, hyperemia, rhinorrhea, or nasal congestion is useful in the differential diagnosis of painful ophthalmoplegia, particularly in the diagnosis of Raeder paratrigeminal neuralgia and hemicrania continua. This case study illustrates a rare presentation of Raeder paratrigeminal neuralgia evolving into hemicrania continua presenting as a painful ophthalmoplegia with multiple cranial nerve involvement. The example supports the

  14. High-order evolving surface finite element method for parabolic problems on evolving surfaces

    OpenAIRE

    Kovács, Balázs

    2016-01-01

    High-order spatial discretisations and full discretisations of parabolic partial differential equations on evolving surfaces are studied. We prove convergence of the high-order evolving surface finite element method, by showing high-order versions of geometric approximation errors and perturbation error estimates and by the careful error analysis of a modified Ritz map. Furthermore, convergence of full discretisations using backward difference formulae and implicit Runge-Kutta methods are als...

  15. Parallel embryonic transcriptional programs evolve under distinct constraints and may enable morphological conservation amidst adaptation.

    Science.gov (United States)

    Malik, Assaf; Gildor, Tsvia; Sher, Noa; Layous, Majed; Ben-Tabou de-Leon, Smadar

    2017-10-01

    Embryonic development evolves by balancing stringent morphological constraints with genetic and environmental variation. The design principle that allows developmental transcriptional programs to conserve embryonic morphology while adapting to environmental changes is still not fully understood. To address this fundamental challenge, we compare developmental transcriptomes of two sea urchin species, Paracentrotus lividus and Strongylocentrotus purpuratus, that shared a common ancestor about 40 million years ago and are geographically distant yet show similar morphology. We find that both developmental and housekeeping genes show highly dynamic and strongly conserved temporal expression patterns. The expression of other gene sets, including homeostasis and response genes, show divergent expression which could result from either evolutionary drift or adaptation to local environmental conditions. The interspecies correlations of developmental gene expressions are highest between morphologically similar developmental time points whereas the interspecies correlations of housekeeping gene expression are high between all the late zygotic time points. Relatedly, the position of the phylotypic stage varies between these two groups of genes: developmental gene expression shows highest conservation at mid-developmental stage, in agreement with the hourglass model while the conservation of housekeeping genes keeps increasing with developmental time. When all genes are combined, the relationship between conservation of gene expression and morphological similarity is partially masked by housekeeping genes and genes with diverged expression. Our study illustrates various transcriptional programs that coexist in the developing embryo and evolve under different constraints. Apparently, morphological constraints underlie the conservation of developmental gene expression while embryonic fitness requires the conservation of housekeeping gene expression and the species

  16. Functional modules of sigma factor regulons guarantee adaptability and evolvability

    Science.gov (United States)

    Binder, Sebastian C.; Eckweiler, Denitsa; Schulz, Sebastian; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Häussler, Susanne; Meyer-Hermann, Michael

    2016-02-01

    The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability.

  17. Evolving roles of circadian rhythms in liver homeostasis and pathology

    Science.gov (United States)

    Chen, Lu; Jia, Leijuan; Yuan, Jie; Sun, Mei; Zhang, Wen; Wang, Peipei; Zuo, Jian; Xu, Zhenyu; Luan, Jiajie

    2016-01-01

    Circadian clock in mammals is determined by a core oscillator in the suprachiasmatic nucleus (SCN) of the hypothalamus and synchronized peripheral clocks in other tissues. The coherent timing systems could sustain robust output of circadian rhythms in response to the entrainment controlled environmentally. Disparate approaches have discovered that clock genes and clock-controlled genes (CCGs) exist in nearly all mammalian cell types and are essential for establishing the mechanisms and complexity of internal time-keeping systems. Accumulating evidence demonstrates that the control of homeostasis and pathology in the liver involves intricate loops of transcriptional and post-translational regulation of clock genes expression. This review will focus on the recent advances with great importance concerning clock rhythms linking liver homeostasis and diseases. We particularly highlight what is currently known of the evolving insights into the mechanisms underlying circadian clock. Eventually, findings during recent years in the field might prompt new circadian-related chronotherapeutic strategies for the diagnosis and treatment of liver diseases by coupling these processes PMID:26843619

  18. Modeling promoter grammars with evolving hidden Markov models

    DEFF Research Database (Denmark)

    Won, Kyoung-Jae; Sandelin, Albin; Marstrand, Troels Torben

    2008-01-01

    factors are involved in the regulation of a set of co-regulated genes. If so, promoters can be modeled with connected regulatory features, where the network of connections is characteristic for a particular mode of regulation. RESULTS: With the goal of automatically deciphering such regulatory structures......MOTIVATION: Describing and modeling biological features of eukaryotic promoters remains an important and challenging problem within computational biology. The promoters of higher eukaryotes in particular display a wide variation in regulatory features, which are difficult to model. Often several......, we present a method that iteratively evolves an ensemble of regulatory grammars using a hidden Markov Model (HMM) architecture composed of interconnected blocks representing transcription factor binding sites (TFBSs) and background regions of promoter sequences. The ensemble approach reduces the risk...

  19. Convergent losses of decay mechanisms and rapid turnover of symbiosis genes in mycorrhizal mutualists.

    Science.gov (United States)

    Kohler, Annegret; Kuo, Alan; Nagy, Laszlo G; Morin, Emmanuelle; Barry, Kerrie W; Buscot, Francois; Canbäck, Björn; Choi, Cindy; Cichocki, Nicolas; Clum, Alicia; Colpaert, Jan; Copeland, Alex; Costa, Mauricio D; Doré, Jeanne; Floudas, Dimitrios; Gay, Gilles; Girlanda, Mariangela; Henrissat, Bernard; Herrmann, Sylvie; Hess, Jaqueline; Högberg, Nils; Johansson, Tomas; Khouja, Hassine-Radhouane; LaButti, Kurt; Lahrmann, Urs; Levasseur, Anthony; Lindquist, Erika A; Lipzen, Anna; Marmeisse, Roland; Martino, Elena; Murat, Claude; Ngan, Chew Y; Nehls, Uwe; Plett, Jonathan M; Pringle, Anne; Ohm, Robin A; Perotto, Silvia; Peter, Martina; Riley, Robert; Rineau, Francois; Ruytinx, Joske; Salamov, Asaf; Shah, Firoz; Sun, Hui; Tarkka, Mika; Tritt, Andrew; Veneault-Fourrey, Claire; Zuccaro, Alga; Tunlid, Anders; Grigoriev, Igor V; Hibbett, David S; Martin, Francis

    2015-04-01

    To elucidate the genetic bases of mycorrhizal lifestyle evolution, we sequenced new fungal genomes, including 13 ectomycorrhizal (ECM), orchid (ORM) and ericoid (ERM) species, and five saprotrophs, which we analyzed along with other fungal genomes. Ectomycorrhizal fungi have a reduced complement of genes encoding plant cell wall-degrading enzymes (PCWDEs), as compared to their ancestral wood decayers. Nevertheless, they have retained a unique array of PCWDEs, thus suggesting that they possess diverse abilities to decompose lignocellulose. Similar functional categories of nonorthologous genes are induced in symbiosis. Of induced genes, 7-38% are orphan genes, including genes that encode secreted effector-like proteins. Convergent evolution of the mycorrhizal habit in fungi occurred via the repeated evolution of a 'symbiosis toolkit', with reduced numbers of PCWDEs and lineage-specific suites of mycorrhiza-induced genes.

  20. De novo ORFs in Drosophila are important to organismal fitness and evolved rapidly from previously non-coding sequences.

    Directory of Open Access Journals (Sweden)

    Josephine A Reinhardt

    Full Text Available How non-coding DNA gives rise to new protein-coding genes (de novo genes is not well understood. Recent work has revealed the origins and functions of a few de novo genes, but common principles governing the evolution or biological roles of these genes are unknown. To better define these principles, we performed a parallel analysis of the evolution and function of six putatively protein-coding de novo genes described in Drosophila melanogaster. Reconstruction of the transcriptional history of de novo genes shows that two de novo genes emerged from novel long non-coding RNAs that arose at least 5 MY prior to evolution of an open reading frame. In contrast, four other de novo genes evolved a translated open reading frame and transcription within the same evolutionary interval suggesting that nascent open reading frames (proto-ORFs, while not required, can contribute to the emergence of a new de novo gene. However, none of the genes arose from proto-ORFs that existed long before expression evolved. Sequence and structural evolution of de novo genes was rapid compared to nearby genes and the structural complexity of de novo genes steadily increases over evolutionary time. Despite the fact that these genes are transcribed at a higher level in males than females, and are most strongly expressed in testes, RNAi experiments show that most of these genes are essential in both sexes during metamorphosis. This lethality suggests that protein coding de novo genes in Drosophila quickly become functionally important.

  1. Evolvability Is an Evolved Ability: The Coding Concept as the Arch-Unit of Natural Selection.

    Science.gov (United States)

    Janković, Srdja; Ćirković, Milan M

    2016-03-01

    Physical processes that characterize living matter are qualitatively distinct in that they involve encoding and transfer of specific types of information. Such information plays an active part in the control of events that are ultimately linked to the capacity of the system to persist and multiply. This algorithmicity of life is a key prerequisite for its Darwinian evolution, driven by natural selection acting upon stochastically arising variations of the encoded information. The concept of evolvability attempts to define the total capacity of a system to evolve new encoded traits under appropriate conditions, i.e., the accessible section of total morphological space. Since this is dependent on previously evolved regulatory networks that govern information flow in the system, evolvability itself may be regarded as an evolved ability. The way information is physically written, read and modified in living cells (the "coding concept") has not changed substantially during the whole history of the Earth's biosphere. This biosphere, be it alone or one of many, is, accordingly, itself a product of natural selection, since the overall evolvability conferred by its coding concept (nucleic acids as information carriers with the "rulebook of meanings" provided by codons, as well as all the subsystems that regulate various conditional information-reading modes) certainly played a key role in enabling this biosphere to survive up to the present, through alterations of planetary conditions, including at least five catastrophic events linked to major mass extinctions. We submit that, whatever the actual prebiotic physical and chemical processes may have been on our home planet, or may, in principle, occur at some time and place in the Universe, a particular coding concept, with its respective potential to give rise to a biosphere, or class of biospheres, of a certain evolvability, may itself be regarded as a unit (indeed the arch-unit) of natural selection.

  2. Survivability is more fundamental than evolvability.

    Directory of Open Access Journals (Sweden)

    Michael E Palmer

    Full Text Available For a lineage to survive over long time periods, it must sometimes change. This has given rise to the term evolvability, meaning the tendency to produce adaptive variation. One lineage may be superior to another in terms of its current standing variation, or it may tend to produce more adaptive variation. However, evolutionary outcomes depend on more than standing variation and produced adaptive variation: deleterious variation also matters. Evolvability, as most commonly interpreted, is not predictive of evolutionary outcomes. Here, we define a predictive measure of the evolutionary success of a lineage that we call the k-survivability, defined as the probability that the lineage avoids extinction for k generations. We estimate the k-survivability using multiple experimental replicates. Because we measure evolutionary outcomes, the initial standing variation, the full spectrum of generated variation, and the heritability of that variation are all incorporated. Survivability also accounts for the decreased joint likelihood of extinction of sub-lineages when they 1 disperse in space, or 2 diversify in lifestyle. We illustrate measurement of survivability with in silico models, and suggest that it may also be measured in vivo using multiple longitudinal replicates. The k-survivability is a metric that enables the quantitative study of, for example, the evolution of 1 mutation rates, 2 dispersal mechanisms, 3 the genotype-phenotype map, and 4 sexual reproduction, in temporally and spatially fluctuating environments. Although these disparate phenomena evolve by well-understood microevolutionary rules, they are also subject to the macroevolutionary constraint of long-term survivability.

  3. Will the Amaranthus tuberculatus Resistance Mechanism to PPO-Inhibiting Herbicides Evolve in Other Amaranthus Species?

    Directory of Open Access Journals (Sweden)

    Chance W. Riggins

    2012-01-01

    Full Text Available Resistance to herbicides that inhibit protoporphyrinogen oxidase (PPO has been slow to evolve and, to date, is confirmed for only four weed species. Two of these species are members of the genus Amaranthus L. Previous research has demonstrated that PPO-inhibitor resistance in A. tuberculatus (Moq. Sauer, the first weed to have evolved this type of resistance, involves a unique codon deletion in the PPX2 gene. Our hypothesis is that A. tuberculatus may have been predisposed to evolving this resistance mechanism due to the presence of a repetitive motif at the mutation site and that lack of this motif in other amaranth species is why PPO-inhibitor resistance has not become more common despite strong herbicide selection pressure. Here we investigate inter- and intraspecific variability of the PPX2 gene—specifically exon 9, which includes the mutation site—in ten amaranth species via sequencing and a PCR-RFLP assay. Few polymorphisms were observed in this region of the gene, and intraspecific variation was observed only in A. quitensis. However, sequencing revealed two distinct repeat patterns encompassing the mutation site. Most notably, A. palmeri S. Watson possesses the same repetitive motif found in A. tuberculatus. We thus predict that A. palmeri will evolve resistance to PPO inhibitors via the same PPX2 codon deletion that evolved in A. tuberculatus.

  4. Present weather and climate: evolving conditions

    Science.gov (United States)

    Hoerling, Martin P; Dettinger, Michael; Wolter, Klaus; Lukas, Jeff; Eischeid, Jon K.; Nemani, Rama; Liebmann, Brant; Kunkel, Kenneth E.

    2013-01-01

    This chapter assesses weather and climate variability and trends in the Southwest, using observed climate and paleoclimate records. It analyzes the last 100 years of climate variability in comparison to the last 1,000 years, and links the important features of evolving climate conditions to river flow variability in four of the region’s major drainage basins. The chapter closes with an assessment of the monitoring and scientific research needed to increase confidence in understanding when climate episodes, events, and phenomena are attributable to human-caused climate change.

  5. f( R) gravity solutions for evolving wormholes

    Science.gov (United States)

    Bhattacharya, Subhra; Chakraborty, Subenoy

    2017-08-01

    The scalar-tensor f( R) theory of gravity is considered in the framework of a simple inhomogeneous space-time model. In this research we use the reconstruction technique to look for possible evolving wormhole solutions within viable f( R) gravity formalism. These f( R) models are then constrained so that they are consistent with existing experimental data. Energy conditions related to the matter threading the wormhole are analyzed graphically and are in general found to obey the null energy conditions (NEC) in regions around the throat, while in the limit f(R)=R, NEC can be violated at large in regions around the throat.

  6. Evolving Random Forest for Preference Learning

    DEFF Research Database (Denmark)

    Abou-Zleikha, Mohamed; Shaker, Noor

    2015-01-01

    This paper introduces a novel approach for pairwise preference learning through a combination of an evolutionary method and random forest. Grammatical evolution is used to describe the structure of the trees in the Random Forest (RF) and to handle the process of evolution. Evolved random forests ...... obtained for predicting pairwise self-reports of users for the three emotional states engagement, frustration and challenge show very promising results that are comparable and in some cases superior to those obtained from state-of-the-art methods....

  7. Sampling Daphnia's expressed genes: preservation, expansion and invention of crustacean genes with reference to insect genomes

    Directory of Open Access Journals (Sweden)

    Bauer Darren J

    2007-07-01

    Full Text Available Abstract Background Functional and comparative studies of insect genomes have shed light on the complement of genes, which in part, account for shared morphologies, developmental programs and life-histories. Contrasting the gene inventories of insects to those of the nematodes provides insight into the genomic changes responsible for their diversification. However, nematodes have weak relationships to insects, as each belongs to separate animal phyla. A better outgroup to distinguish lineage specific novelties would include other members of Arthropoda. For example, crustaceans are close allies to the insects (together forming Pancrustacea and their fascinating aquatic lifestyle provides an important comparison for understanding the genetic basis of adaptations to life on land versus life in water. Results This study reports on the first characterization of cDNA libraries and sequences for the model crustacean Daphnia pulex. We analyzed 1,546 ESTs of which 1,414 represent approximately 787 nuclear genes, by measuring their sequence similarities with insect and nematode proteomes. The provisional annotation of genes is supported by expression data from microarray studies described in companion papers. Loci expected to be shared between crustaceans and insects because of their mutual biological features are identified, including genes for reproduction, regulation and cellular processes. We identify genes that are likely derived within Pancrustacea or lost within the nematodes. Moreover, lineage specific gene family expansions are identified, which suggest certain biological demands associated with their ecological setting. In particular, up to seven distinct ferritin loci are found in Daphnia compared to three in most insects. Finally, a substantial fraction of the sampled gene transcripts shares no sequence similarity with those from other arthropods. Genes functioning during development and reproduction are comparatively well conserved between

  8. Sampling Daphnia's expressed genes: preservation, expansion and invention of crustacean genes with reference to insect genomes.

    Science.gov (United States)

    Colbourne, John K; Eads, Brian D; Shaw, Joseph; Bohuski, Elizabeth; Bauer, Darren J; Andrews, Justen

    2007-07-06

    Functional and comparative studies of insect genomes have shed light on the complement of genes, which in part, account for shared morphologies, developmental programs and life-histories. Contrasting the gene inventories of insects to those of the nematodes provides insight into the genomic changes responsible for their diversification. However, nematodes have weak relationships to insects, as each belongs to separate animal phyla. A better outgroup to distinguish lineage specific novelties would include other members of Arthropoda. For example, crustaceans are close allies to the insects (together forming Pancrustacea) and their fascinating aquatic lifestyle provides an important comparison for understanding the genetic basis of adaptations to life on land versus life in water. This study reports on the first characterization of cDNA libraries and sequences for the model crustacean Daphnia pulex. We analyzed 1,546 ESTs of which 1,414 represent approximately 787 nuclear genes, by measuring their sequence similarities with insect and nematode proteomes. The provisional annotation of genes is supported by expression data from microarray studies described in companion papers. Loci expected to be shared between crustaceans and insects because of their mutual biological features are identified, including genes for reproduction, regulation and cellular processes. We identify genes that are likely derived within Pancrustacea or lost within the nematodes. Moreover, lineage specific gene family expansions are identified, which suggest certain biological demands associated with their ecological setting. In particular, up to seven distinct ferritin loci are found in Daphnia compared to three in most insects. Finally, a substantial fraction of the sampled gene transcripts shares no sequence similarity with those from other arthropods. Genes functioning during development and reproduction are comparatively well conserved between crustaceans and insects. By contrast, genes that

  9. The monosaccharide transporter gene family in land plants is ancient and shows differential subfamily expression and expansion across lineages

    Directory of Open Access Journals (Sweden)

    Thomas Michael A

    2006-08-01

    Full Text Available Abstract Background In plants, tandem, segmental and whole-genome duplications are prevalent, resulting in large numbers of duplicate loci. Recent studies suggest that duplicate genes diverge predominantly through the partitioning of expression and that breadth of gene expression is related to the rate of gene duplication and protein sequence evolution. Here, we utilize expressed sequence tag (EST data to study gene duplication and expression patterns in the monosaccharide transporter (MST gene family across the land plants. In Arabidopsis, there are 53 MST genes that form seven distinct subfamilies. We created profile hidden Markov models of each subfamily and searched EST databases representing diverse land plant lineages to address the following questions: 1 Are homologs of each Arabidopsis subfamily present in the earliest land plants? 2 Do expression patterns among subfamilies and individual genes within subfamilies differ across lineages? 3 Has gene duplication within each lineage resulted in lineage-specific expansion patterns? We also looked for correlations between relative EST database representation in Arabidopsis and similarity to orthologs in early lineages. Results Homologs of all seven MST subfamilies were present in land plants at least 400 million years ago. Subfamily expression levels vary across lineages with greater relative expression of the STP, ERD6-like, INT and PLT subfamilies in the vascular plants. In the large EST databases of the moss, gymnosperm, monocot and eudicot lineages, EST contig construction reveals that MST subfamilies have experienced lineage-specific expansions. Large subfamily expansions appear to be due to multiple gene duplications arising from single ancestral genes. In Arabidopsis, one or a few genes within most subfamilies have much higher EST database representation than others. Most highly represented (broadly expressed genes in Arabidopsis have best match orthologs in early divergent lineages

  10. Netgram: Visualizing Communities in Evolving Networks.

    Directory of Open Access Journals (Sweden)

    Raghvendra Mall

    Full Text Available Real-world complex networks are dynamic in nature and change over time. The change is usually observed in the interactions within the network over time. Complex networks exhibit community like structures. A key feature of the dynamics of complex networks is the evolution of communities over time. Several methods have been proposed to detect and track the evolution of these groups over time. However, there is no generic tool which visualizes all the aspects of group evolution in dynamic networks including birth, death, splitting, merging, expansion, shrinkage and continuation of groups. In this paper, we propose Netgram: a tool for visualizing evolution of communities in time-evolving graphs. Netgram maintains evolution of communities over 2 consecutive time-stamps in tables which are used to create a query database using the sql outer-join operation. It uses a line-based visualization technique which adheres to certain design principles and aesthetic guidelines. Netgram uses a greedy solution to order the initial community information provided by the evolutionary clustering technique such that we have fewer line cross-overs in the visualization. This makes it easier to track the progress of individual communities in time evolving graphs. Netgram is a generic toolkit which can be used with any evolutionary community detection algorithm as illustrated in our experiments. We use Netgram for visualization of topic evolution in the NIPS conference over a period of 11 years and observe the emergence and merging of several disciplines in the field of information processing systems.

  11. Evolving MEMS Resonator Designs for Fabrication

    Science.gov (United States)

    Hornby, Gregory S.; Kraus, William F.; Lohn, Jason D.

    2008-01-01

    Because of their small size and high reliability, microelectromechanical (MEMS) devices have the potential to revolution many areas of engineering. As with conventionally-sized engineering design, there is likely to be a demand for the automated design of MEMS devices. This paper describes our current status as we progress toward our ultimate goal of using an evolutionary algorithm and a generative representation to produce designs of a MEMS device and successfully demonstrate its transfer to an actual chip. To produce designs that are likely to transfer to reality, we present two ways to modify evaluation of designs. The first is to add location noise, differences between the actual dimensions of the design and the design blueprint, which is a technique we have used for our work in evolving antennas and robots. The second method is to add prestress to model the warping that occurs during the extreme heat of fabrication. In future we expect to fabricate and test some MEMS resonators that are evolved in this way.

  12. Netgram: Visualizing Communities in Evolving Networks

    Science.gov (United States)

    Mall, Raghvendra; Langone, Rocco; Suykens, Johan A. K.

    2015-01-01

    Real-world complex networks are dynamic in nature and change over time. The change is usually observed in the interactions within the network over time. Complex networks exhibit community like structures. A key feature of the dynamics of complex networks is the evolution of communities over time. Several methods have been proposed to detect and track the evolution of these groups over time. However, there is no generic tool which visualizes all the aspects of group evolution in dynamic networks including birth, death, splitting, merging, expansion, shrinkage and continuation of groups. In this paper, we propose Netgram: a tool for visualizing evolution of communities in time-evolving graphs. Netgram maintains evolution of communities over 2 consecutive time-stamps in tables which are used to create a query database using the sql outer-join operation. It uses a line-based visualization technique which adheres to certain design principles and aesthetic guidelines. Netgram uses a greedy solution to order the initial community information provided by the evolutionary clustering technique such that we have fewer line cross-overs in the visualization. This makes it easier to track the progress of individual communities in time evolving graphs. Netgram is a generic toolkit which can be used with any evolutionary community detection algorithm as illustrated in our experiments. We use Netgram for visualization of topic evolution in the NIPS conference over a period of 11 years and observe the emergence and merging of several disciplines in the field of information processing systems. PMID:26356538

  13. BOOK REVIEW: OPENING SCIENCE, THE EVOLVING GUIDE ...

    Science.gov (United States)

    The way we get our funding, collaborate, do our research, and get the word out has evolved over hundreds of years but we can imagine a more open science world, largely facilitated by the internet. The movement towards this more open way of doing and presenting science is coming, and it is not taking hundreds of years. If you are interested in these trends, and would like to find out more about where this is all headed and what it means to you, consider downloding Opening Science, edited by Sönke Bartling and Sascha Friesike, subtitled The Evolving Guide on How the Internet is Changing Research, Collaboration, and Scholarly Publishing. In 26 chapters by various authors from a range of disciplines the book explores the developing world of open science, starting from the first scientific revolution and bringing us to the next scientific revolution, sometimes referred to as “Science 2.0”. Some of the articles deal with the impact of the changing landscape of how science is done, looking at the impact of open science on Academia, or journal publishing, or medical research. Many of the articles look at the uses, pitfalls, and impact of specific tools, like microblogging (think Twitter), social networking, and reference management. There is lots of discussion and definition of terms you might use or misuse like “altmetrics” and “impact factor”. Science will probably never be completely open, and Twitter will probably never replace the journal article,

  14. Protein coalitions in a core mammalian biochemical network linked by rapidly evolving proteins

    Directory of Open Access Journals (Sweden)

    Tsoka Sophia

    2011-05-01

    Full Text Available Abstract Background Cellular ATP levels are generated by glucose-stimulated mitochondrial metabolism and determine metabolic responses, such as glucose-stimulated insulin secretion (GSIS from the β-cells of pancreatic islets. We describe an analysis of the evolutionary processes affecting the core enzymes involved in glucose-stimulated insulin secretion in mammals. The proteins involved in this system belong to ancient enzymatic pathways: glycolysis, the TCA cycle and oxidative phosphorylation. Results We identify two sets of proteins, or protein coalitions, in this group of 77 enzymes with distinct evolutionary patterns. Members of the glycolysis, TCA cycle, metabolite transport, pyruvate and NADH shuttles have low rates of protein sequence evolution, as inferred from a human-mouse comparison, and relatively high rates of evolutionary gene duplication. Respiratory chain and glutathione pathway proteins evolve faster, exhibiting lower rates of gene duplication. A small number of proteins in the system evolve significantly faster than co-pathway members and may serve as rapidly evolving adapters, linking groups of co-evolving genes. Conclusions Our results provide insights into the evolution of the involved proteins. We find evidence for two coalitions of proteins and the role of co-adaptation in protein evolution is identified and could be used in future research within a functional context.

  15. The evolving genetic risk for sporadic ALS.

    Science.gov (United States)

    Gibson, Summer B; Downie, Jonathan M; Tsetsou, Spyridoula; Feusier, Julie E; Figueroa, Karla P; Bromberg, Mark B; Jorde, Lynn B; Pulst, Stefan M

    2017-07-18

    To estimate the genetic risk conferred by known amyotrophic lateral sclerosis (ALS)-associated genes to the pathogenesis of sporadic ALS (SALS) using variant allele frequencies combined with predicted variant pathogenicity. Whole exome sequencing and repeat expansion PCR of C9orf72 and ATXN2 were performed on 87 patients of European ancestry with SALS seen at the University of Utah. DNA variants that change the protein coding sequence of 31 ALS-associated genes were annotated to determine which were rare and deleterious as predicted by MetaSVM. The percentage of patients with SALS with a rare and deleterious variant or repeat expansion in an ALS-associated gene was calculated. An odds ratio analysis was performed comparing the burden of ALS-associated genes in patients with SALS vs 324 normal controls. Nineteen rare nonsynonymous variants in an ALS-associated gene, 2 of which were found in 2 different individuals, were identified in 21 patients with SALS. Further, 5 deleterious C9orf72 and 2 ATXN2 repeat expansions were identified. A total of 17.2% of patients with SALS had a rare and deleterious variant or repeat expansion in an ALS-associated gene. The genetic burden of ALS-associated genes in patients with SALS as predicted by MetaSVM was significantly higher than in normal controls. Previous analyses have identified SALS-predisposing variants only in terms of their rarity in normal control populations. By incorporating variant pathogenicity as well as variant frequency, we demonstrated that the genetic risk contributed by these genes for SALS is substantially lower than previous estimates. © 2017 American Academy of Neurology.

  16. Unresolved orthology and peculiar coding sequence properties of lamprey genes: the KCNA gene family as test case

    Directory of Open Access Journals (Sweden)

    Kuraku Shigehiro

    2011-06-01

    Full Text Available Abstract Background In understanding the evolutionary process of vertebrates, cyclostomes (hagfishes and lamprey occupy crucial positions. Resolving molecular phylogenetic relationships of cyclostome genes with gnathostomes (jawed vertebrates genes is indispensable in deciphering both the species tree and gene trees. However, molecular phylogenetic analyses, especially those including lamprey genes, have produced highly discordant results between gene families. To efficiently scrutinize this problem using partial genome assemblies of early vertebrates, we focused on the potassium voltage-gated channel, shaker-related (KCNA family, whose members are mostly single-exon. Results Seven sea lamprey KCNA genes as well as six elephant shark genes were identified, and their orthologies to bony vertebrate subgroups were assessed. In contrast to robustly supported orthology of the elephant shark genes to gnathostome subgroups, clear orthology of any sea lamprey gene could not be established. Notably, sea lamprey KCNA sequences displayed unique codon usage pattern and amino acid composition, probably associated with exceptionally high GC-content in their coding regions. This lamprey-specific property of coding sequences was also observed generally for genes outside this gene family. Conclusions Our results suggest that secondary modifications of sequence properties unique to the lamprey lineage may be one of the factors preventing robust orthology assessments of lamprey genes, which deserves further genome-wide validation. The lamprey lineage-specific alteration of protein-coding sequence properties needs to be taken into consideration in tackling the key questions about early vertebrate evolution.

  17. The Evolving Diagnostic and Genetic Landscapes of Autism Spectrum Disorder.

    Science.gov (United States)

    Ziats, Mark N; Rennert, Owen M

    2016-01-01

    The autism spectrum disorders (ASD) are a heterogeneous set of neurodevelopmental syndromes defined by impairments in verbal and non-verbal communication, restricted social interaction, and the presence of stereotyped patterns of behavior. The prevalence of ASD is rising, and the diagnostic criteria and clinical perspectives on the disorder continue to evolve in parallel. Although the majority of individuals with ASD will not have an identifiable genetic cause, almost 25% of cases have identifiable causative DNA variants. The rapidly improving ability to identify genetic mutations because of advances in next generation sequencing, coupled with previous epidemiological studies demonstrating high heritability of ASD, have led to many recent attempts to identify causative genetic mutations underlying the ASD phenotype. However, although hundreds of mutations have been identified to date, they are either rare variants affecting only a handful of ASD patients, or are common variants in the general population conferring only a small risk for ASD. Furthermore, the genes implicated thus far are heterogeneous in their structure and function, hampering attempts to understand shared molecular mechanisms among all ASD patients; an understanding that is crucial for the development of targeted diagnostics and therapies. However, new work is beginning to suggest that the heterogeneous set of genes implicated in ASD may ultimately converge on a few common pathways. In this review, we discuss the parallel evolution of our diagnostic and genetic understanding of autism spectrum disorders, and highlight recent attempts to infer common biology underlying this complicated syndrome.

  18. The evolving diagnostic and genetic landscapes of autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Mark Nicholas Ziats

    2016-04-01

    Full Text Available The autism spectrum disorders (ASD are a heterogeneous set of neurodevelopmental syndromes defined by impairments in verbal and non-verbal communication, restricted social interaction, and the presence of stereotyped patterns of behavior. The prevalence of ASD is rising, and the diagnostic criteria and clinical perspectives on the disorder continue to evolve in parallel. Although the majority of individuals with ASD will not have an identifiable genetic cause, almost 25% of cases have identifiable causative DNA variants. The rapidly improving ability to identify genetic mutations because of advances in next generation sequencing, coupled with previous epidemiological studies demonstrating high heritability of ASD, have led to many recent attempts to identify causative genetic mutations underlying the ASD phenotype. However, although hundreds of mutations have been identified to date, they are either rare variants affecting only a handful of ASD patients, or are common variants in the general population conferring only a small risk for ASD. Furthermore, the genes implicated thus far are heterogeneous in their structure and function, hampering attempts to understand shared molecular mechanisms among all ASD patients; an understanding that is crucial for the development of targeted diagnostics and therapies. However, new work is beginning to suggest that the heterogeneous set of genes implicated in ASD may ultimately converge on a few common pathways. In this review, we discuss the parallel evolution of our diagnostic and genetic understanding of autism spectrum disorders, and highlight recent attempts to infer common biology underlying this complicated syndrome.

  19. Forces shaping the fastest evolving regions in the human genome.

    Directory of Open Access Journals (Sweden)

    Katherine S Pollard

    2006-10-01

    Full Text Available Comparative genomics allow us to search the human genome for segments that were extensively changed in the last approximately 5 million years since divergence from our common ancestor with chimpanzee, but are highly conserved in other species and thus are likely to be functional. We found 202 genomic elements that are highly conserved in vertebrates but show evidence of significantly accelerated substitution rates in human. These are mostly in non-coding DNA, often near genes associated with transcription and DNA binding. Resequencing confirmed that the five most accelerated elements are dramatically changed in human but not in other primates, with seven times more substitutions in human than in chimp. The accelerated elements, and in particular the top five, show a strong bias for adenine and thymine to guanine and cytosine nucleotide changes and are disproportionately located in high recombination and high guanine and cytosine content environments near telomeres, suggesting either biased gene conversion or isochore selection. In addition, there is some evidence of directional selection in the regions containing the two most accelerated regions. A combination of evolutionary forces has contributed to accelerated evolution of the fastest evolving elements in the human genome.

  20. Tumor biology and cancer therapy – an evolving relationship

    Directory of Open Access Journals (Sweden)

    Lother Ulrike

    2009-08-01

    Full Text Available Abstract The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pathways underlie cancer, and not just altered genes. Thus, an effective therapeutic agent will sometimes have to target downstream parts of a signaling pathway or physiological effects rather than individual genes. In addition, over the past few years increasing evidence has suggested that solid tumors represent a very heterogeneous group of cells with different susceptibility to cancer therapy. Thus, since therapeutic concepts and pathophysiological understanding are continuously evolving a combination of current concepts in tumor therapy and tumor biology is needed. This review aims to present current problems of cancer therapy by highlighting exemplary results from recent clinical trials with colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying reasons.

  1. Meiosis evolves: adaptation to external and internal environments.

    Science.gov (United States)

    Bomblies, Kirsten; Higgins, James D; Yant, Levi

    2015-10-01

    306 I. 306 II. 307 III. 312 IV. 317 V. 318 319 References 319 SUMMARY: Meiosis is essential for the fertility of most eukaryotes and its structures and progression are conserved across kingdoms. Yet many of its core proteins show evidence of rapid or adaptive evolution. What drives the evolution of meiosis proteins? How can constrained meiotic processes be modified in response to challenges without compromising their essential functions? In surveying the literature, we found evidence of two especially potent challenges to meiotic chromosome segregation that probably necessitate adaptive evolutionary responses: whole-genome duplication and abiotic environment, especially temperature. Evolutionary solutions to both kinds of challenge are likely to involve modification of homologous recombination and synapsis, probably via adjustments of core structural components important in meiosis I. Synthesizing these findings with broader patterns of meiosis gene evolution suggests that the structural components of meiosis coevolve as adaptive modules that may change in primary sequence and function while maintaining three-dimensional structures and protein interactions. The often sharp divergence of these genes among species probably reflects periodic modification of entire multiprotein complexes driven by genomic or environmental changes. We suggest that the pressures that cause meiosis to evolve to maintain fertility may cause pleiotropic alterations of global crossover rates. We highlight several important areas for future research. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  2. Glycerol stress in Saccharomyces cerevisiae: Cellular responses and evolved adaptations.

    Science.gov (United States)

    Mattenberger, Florian; Sabater-Muñoz, Beatriz; Hallsworth, John E; Fares, Mario A

    2017-03-01

    Glycerol synthesis is key to central metabolism and stress biology in Saccharomyces cerevisiae, yet the cellular adjustments needed to respond and adapt to glycerol stress are little understood. Here, we determined impacts of acute and chronic exposures to glycerol stress in S. cerevisiae. Glycerol stress can result from an increase of glycerol concentration in the medium due to the S. cerevisiae fermenting activity or other metabolic activities. Acute glycerol-stress led to a 50% decline in growth rate and altered transcription of more than 40% of genes. The increased genetic diversity in S. cerevisiae population, which had evolved in the standard nutrient medium for hundreds of generations, led to an increase in growth rate and altered transcriptome when such population was transferred to stressful media containing a high concentration of glycerol; 0.41 M (0.990 water activity). Evolution of S. cerevisiae populations during a 10-day period in the glycerol-containing medium led to transcriptome changes and readjustments to improve control of glycerol flux across the membrane, regulation of cell cycle, and more robust stress response; and a remarkable increase of growth rate under glycerol stress. Most of the observed regulatory changes arose in duplicated genes. These findings elucidate the physiological mechanisms, which underlie glycerol-stress response, and longer-term adaptations, in S. cerevisiae; they also have implications for enigmatic aspects of the ecology of this otherwise well-characterized yeast. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Evolvability as a Quality Attribute of Software Architectures

    NARCIS (Netherlands)

    Ciraci, S.; van den Broek, P.M.; Duchien, Laurence; D'Hondt, Maja; Mens, Tom

    We review the definition of evolvability as it appears on the literature. In particular, the concept of software evolvability is compared with other system quality attributes, such as adaptability, maintainability and modifiability.

  4. A rapidly evolving secretome builds and patterns a sea shell

    Directory of Open Access Journals (Sweden)

    Green Kathryn

    2006-11-01

    Full Text Available Abstract Background Instructions to fabricate mineralized structures with distinct nanoscale architectures, such as seashells and coral and vertebrate skeletons, are encoded in the genomes of a wide variety of animals. In mollusks, the mantle is responsible for the extracellular production of the shell, directing the ordered biomineralization of CaCO3 and the deposition of architectural and color patterns. The evolutionary origins of the ability to synthesize calcified structures across various metazoan taxa remain obscure, with only a small number of protein families identified from molluskan shells. The recent sequencing of a wide range of metazoan genomes coupled with the analysis of gene expression in non-model animals has allowed us to investigate the evolution and process of biomineralization in gastropod mollusks. Results Here we show that over 25% of the genes expressed in the mantle of the vetigastropod Haliotis asinina encode secreted proteins, indicating that hundreds of proteins are likely to be contributing to shell fabrication and patterning. Almost 85% of the secretome encodes novel proteins; remarkably, only 19% of these have identifiable homologues in the full genome of the patellogastropod Lottia scutum. The spatial expression profiles of mantle genes that belong to the secretome is restricted to discrete mantle zones, with each zone responsible for the fabrication of one of the structural layers of the shell. Patterned expression of a subset of genes along the length of the mantle is indicative of roles in shell ornamentation. For example, Has-sometsuke maps precisely to pigmentation patterns in the shell, providing the first case of a gene product to be involved in molluskan shell pigmentation. We also describe the expression of two novel genes involved in nacre (mother of pearl deposition. Conclusion The unexpected complexity and evolvability of this secretome and the modular design of the molluskan mantle enables

  5. Tracking correlated, simultaneously evolving target populations, II

    Science.gov (United States)

    Mahler, Ronald

    2017-05-01

    This paper is the sixth in a series aimed at weakening the independence assumptions that are typically presumed in multitarget tracking. Earlier papers investigated Bayes …lters that propagate the correlations between two evolving multitarget systems. Last year at this conference we attempted to derive PHD …lter-type approximations that account for both spatial correlation and cardinality correlation (i.e., correlation between the target numbers of the two systems). Unfortunately, this approach required heuristic models of both clutter and target appearance in order to incorporate both spatial and cardinality correlation. This paper describes a fully rigorous approach- provided, however, that spatial correlation between the two populations is ignored and only their cardinality correlations are taken into account. We derive the time-update and measurement-update equations for a CPHD …lter describing the evolution of such correlated multitarget populations.

  6. Resiliently evolving supply-demand networks.

    Science.gov (United States)

    Rubido, Nicolás; Grebogi, Celso; Baptista, Murilo S

    2014-01-01

    The ability to design a transport network such that commodities are brought from suppliers to consumers in a steady, optimal, and stable way is of great importance for distribution systems nowadays. In this work, by using the circuit laws of Kirchhoff and Ohm, we provide the exact capacities of the edges that an optimal supply-demand network should have to operate stably under perturbations, i.e., without overloading. The perturbations we consider are the evolution of the connecting topology, the decentralization of hub sources or sinks, and the intermittence of supplier and consumer characteristics. We analyze these conditions and the impact of our results, both on the current United Kingdom power-grid structure and on numerically generated evolving archetypal network topologies.

  7. A local-world evolving hypernetwork model

    Science.gov (United States)

    Yang, Guang-Yong; Liu, Jian-Guo

    2014-01-01

    Complex hypernetworks are ubiquitous in the real system. It is very important to investigate the evolution mechanisms. In this paper, we present a local-world evolving hypernetwork model by taking into account the hyperedge growth and local-world hyperedge preferential attachment mechanisms. At each time step, a newly added hyperedge encircles a new coming node and a number of nodes from a randomly selected local world. The number of the selected nodes from the local world obeys the uniform distribution and its mean value is m. The analytical and simulation results show that the hyperdegree approximately obeys the power-law form and the exponent of hyperdegree distribution is γ = 2 + 1/m. Furthermore, we numerically investigate the node degree, hyperedge degree, clustering coefficient, as well as the average distance, and find that the hypernetwork model shares the scale-free and small-world properties, which shed some light for deeply understanding the evolution mechanism of the real systems.

  8. The Evolving Theory of Evolutionary Radiations.

    Science.gov (United States)

    Simões, M; Breitkreuz, L; Alvarado, M; Baca, S; Cooper, J C; Heins, L; Herzog, K; Lieberman, B S

    2016-01-01

    Evolutionary radiations have intrigued biologists for more than 100 years, and our understanding of the patterns and processes associated with these radiations continues to grow and evolve. Recently it has been recognized that there are many different types of evolutionary radiation beyond the well-studied adaptive radiations. We focus here on multifarious types of evolutionary radiations, paying special attention to the abiotic factors that might trigger diversification in clades. We integrate concepts such as exaptation, species selection, coevolution, and the turnover-pulse hypothesis (TPH) into the theoretical framework of evolutionary radiations. We also discuss other phenomena that are related to, but distinct from, evolutionary radiations that have relevance for evolutionary biology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Epidemic spreading on evolving signed networks

    CERN Document Server

    Saeedian, M; Jafari, G R; Kertesz, J

    2016-01-01

    Most studies of disease spreading consider the underlying social network as obtained without the contagion, though epidemic influences peoples willingness to contact others: A friendly contact may be turned to unfriendly to avoid infection. We study the susceptible-infected (SI) disease spreading model on signed networks, in which each edge is associated with a positive or negative sign representing the friendly or unfriendly relation between its end nodes. In a signed network, according to Heiders theory, edge signs evolve such that finally a state of structural balance is achieved, corresponding to no frustration in physics terms. However, the danger of infection affects the evolution of its edge signs. To describe the coupled problem of the sign evolution and disease spreading, we generalize the notion of structural balance by taking into account the state of the nodes. We introduce an energy function and carry out Monte-Carlo simulations on complete networks to test the energy landscape, where we find loc...

  10. Finch: A System for Evolving Java (Bytecode)

    Science.gov (United States)

    Orlov, Michael; Sipper, Moshe

    The established approach in genetic programming (GP) involves the definition of functions and terminals appropriate to the problem at hand, after which evolution of expressions using these definitions takes place. We have recently developed a system, dubbed FINCH (Fertile Darwinian Bytecode Harvester), to evolutionarily improve actual, extant software, which was not intentionally written for the purpose of serving as a GP representation in particular, nor for evolution in general. This is in contrast to existing work that uses restricted subsets of the Java bytecode instruction set as a representation language for individuals in genetic programming. The ability to evolve Java programs will hopefully lead to a valuable new tool in the software engineer's toolkit.

  11. Key role of lipid management in nitrogen and aroma metabolism in an evolved wine yeast strain.

    Science.gov (United States)

    Rollero, Stéphanie; Mouret, Jean-Roch; Sanchez, Isabelle; Camarasa, Carole; Ortiz-Julien, Anne; Sablayrolles, Jean-Marie; Dequin, Sylvie

    2016-02-09

    Fermentative aromas play a key role in the organoleptic profile of young wines. Their production depends both on yeast strain and fermentation conditions. A present-day trend in the wine industry consists in developing new strains with aromatic properties using adaptive evolution approaches. An evolved strain, Affinity™ ECA5, overproducing esters, was recently obtained. In this study, dynamics of nitrogen consumption and of the fermentative aroma synthesis of the evolved and its ancestral strains were compared and coupled with a transcriptomic analysis approach to better understand the metabolic reshaping of Affinity™ ECA5. Nitrogen assimilation was different between the two strains, particularly amino acids transported by carriers regulated by nitrogen catabolite repression. We also observed differences in the kinetics of fermentative aroma production, especially in the bioconversion of higher alcohols into acetate esters. Finally, transcriptomic data showed that the enhanced bioconversion into acetate esters by the evolved strain was associated with the repression of genes involved in sterol biosynthesis rather than an enhanced expression of ATF1 and ATF2 (genes coding for the enzymes responsible for the synthesis of acetate esters from higher alcohols). An integrated approach to yeast metabolism-combining transcriptomic analyses and online monitoring data-showed differences between the two strains at different levels. Differences in nitrogen source consumption were observed suggesting modifications of NCR in the evolved strain. Moreover, the evolved strain showed a different way of managing the lipid source, which notably affected the production of acetate esters, likely because of a greater availability of acetyl-CoA for the evolved strain.

  12. The evolving energy budget of accretionary wedges

    Science.gov (United States)

    McBeck, Jessica; Cooke, Michele; Maillot, Bertrand; Souloumiac, Pauline

    2017-04-01

    The energy budget of evolving accretionary systems reveals how deformational processes partition energy as faults slip, topography uplifts, and layer-parallel shortening produces distributed off-fault deformation. The energy budget provides a quantitative framework for evaluating the energetic contribution or consumption of diverse deformation mechanisms. We investigate energy partitioning in evolving accretionary prisms by synthesizing data from physical sand accretion experiments and numerical accretion simulations. We incorporate incremental strain fields and cumulative force measurements from two suites of experiments to design numerical simulations that represent accretionary wedges with stronger and weaker detachment faults. One suite of the physical experiments includes a basal glass bead layer and the other does not. Two physical experiments within each suite implement different boundary conditions (stable base versus moving base configuration). Synthesizing observations from the differing base configurations reduces the influence of sidewall friction because the force vector produced by sidewall friction points in opposite directions depending on whether the base is fixed or moving. With the numerical simulations, we calculate the energy budget at two stages of accretion: at the maximum force preceding the development of the first thrust pair, and at the minimum force following the development of the pair. To identify the appropriate combination of material and fault properties to apply in the simulations, we systematically vary the Young's modulus and the fault static and dynamic friction coefficients in numerical accretion simulations, and identify the set of parameters that minimizes the misfit between the normal force measured on the physical backwall and the numerically simulated force. Following this derivation of the appropriate material and fault properties, we calculate the components of the work budget in the numerical simulations and in the

  13. Relationship among phenotypic plasticity, phenotypic fluctuations, robustness, and evolvability; Waddington's legacy revisited under the spirit of Einstein.

    Science.gov (United States)

    Kaneko, Kunihiko

    2009-10-01

    Questions on possible relationship between phenotypic plasticity and evolvability, and that between robustness and evolution have been addressed over decades in the field of evolution-development. Based on laboratory evolution experiments and numerical simulations of gene expression dynamics model with an evolving transcription network, we propose quantitative relationships on plasticity, phenotypic fluctuations, and evolvability. By introducing an evolutionary stability assumption on the distribution of phenotype and genotype, the proportionality among phenotypic plasticity against environmental change, variances of phenotype fluctuations of genetic and developmental origins, and evolution speed is obtained. The correlation between developmental robustness to noise and evolutionary robustness to mutation is analysed by simulations of the gene network model. These results provide quantitative formulation on canalization and genetic assimilation, in terms of fluctuations of gene expression levels.

  14. On the Critical Role of Divergent Selection in Evolvability

    Directory of Open Access Journals (Sweden)

    Joel Lehman

    2016-08-01

    Full Text Available An ambitious goal in evolutionary robotics is to evolve increasingly complex robotic behaviors with minimal human design effort. Reaching this goal requires evolutionary algorithms that can unlock from genetic encodings their latent potential for evolvability. One issue clouding this goal is conceptual confusion about evolvability, which often obscures the aspects of evolvability that are important or desirable. The danger from such confusion is that it may establish unrealistic goals for evolvability that prove unproductive in practice. An important issue separate from conceptual confusion is the common misalignment between selection and evolvability in evolutionary robotics. While more expressive encodings can represent higher-level adaptations (e.g. sexual reproduction or developmental systems that increase long-term evolutionary potential (i.e. evolvability, realizing such potential requires gradients of fitness and evolvability to align. In other words, selection is often a critical factor limiting increasing evolvability. Thus, drawing from a series of recent papers, this article seeks to both (1 clarify and focus the ways in which the term evolvability is used within artificial evolution, and (2 argue for the importance of one type of selection, i.e. divergent selection, for enabling evolvability. The main argument is that there is a fundamental connection between divergent selection and evolvability (on both the individual and population level that does not hold for typical goal-oriented selection. The conclusion is that selection pressure plays a critical role in realizing the potential for evolvability, and that divergent selection in particular provides a principled mechanism for encouraging evolvability in artificial evolution.

  15. How does cognition evolve? Phylogenetic comparative psychology

    Science.gov (United States)

    Matthews, Luke J.; Hare, Brian A.; Nunn, Charles L.; Anderson, Rindy C.; Aureli, Filippo; Brannon, Elizabeth M.; Call, Josep; Drea, Christine M.; Emery, Nathan J.; Haun, Daniel B. M.; Herrmann, Esther; Jacobs, Lucia F.; Platt, Michael L.; Rosati, Alexandra G.; Sandel, Aaron A.; Schroepfer, Kara K.; Seed, Amanda M.; Tan, Jingzhi; van Schaik, Carel P.; Wobber, Victoria

    2014-01-01

    Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution. PMID:21927850

  16. Approximating centrality in evolving graphs: toward sublinearity

    Science.gov (United States)

    Priest, Benjamin W.; Cybenko, George

    2017-05-01

    The identification of important nodes is a ubiquitous problem in the analysis of social networks. Centrality indices (such as degree centrality, closeness centrality, betweenness centrality, PageRank, and others) are used across many domains to accomplish this task. However, the computation of such indices is expensive on large graphs. Moreover, evolving graphs are becoming increasingly important in many applications. It is therefore desirable to develop on-line algorithms that can approximate centrality measures using memory sublinear in the size of the graph. We discuss the challenges facing the semi-streaming computation of many centrality indices. In particular, we apply recent advances in the streaming and sketching literature to provide a preliminary streaming approximation algorithm for degree centrality utilizing CountSketch and a multi-pass semi-streaming approximation algorithm for closeness centrality leveraging a spanner obtained through iteratively sketching the vertex-edge adjacency matrix. We also discuss possible ways forward for approximating betweenness centrality, as well as spectral measures of centrality. We provide a preliminary result using sketched low-rank approximations to approximate the output of the HITS algorithm.

  17. How does cognition evolve? Phylogenetic comparative psychology.

    Science.gov (United States)

    MacLean, Evan L; Matthews, Luke J; Hare, Brian A; Nunn, Charles L; Anderson, Rindy C; Aureli, Filippo; Brannon, Elizabeth M; Call, Josep; Drea, Christine M; Emery, Nathan J; Haun, Daniel B M; Herrmann, Esther; Jacobs, Lucia F; Platt, Michael L; Rosati, Alexandra G; Sandel, Aaron A; Schroepfer, Kara K; Seed, Amanda M; Tan, Jingzhi; van Schaik, Carel P; Wobber, Victoria

    2012-03-01

    Now more than ever animal studies have the potential to test hypotheses regarding how cognition evolves. Comparative psychologists have developed new techniques to probe the cognitive mechanisms underlying animal behavior, and they have become increasingly skillful at adapting methodologies to test multiple species. Meanwhile, evolutionary biologists have generated quantitative approaches to investigate the phylogenetic distribution and function of phenotypic traits, including cognition. In particular, phylogenetic methods can quantitatively (1) test whether specific cognitive abilities are correlated with life history (e.g., lifespan), morphology (e.g., brain size), or socio-ecological variables (e.g., social system), (2) measure how strongly phylogenetic relatedness predicts the distribution of cognitive skills across species, and (3) estimate the ancestral state of a given cognitive trait using measures of cognitive performance from extant species. Phylogenetic methods can also be used to guide the selection of species comparisons that offer the strongest tests of a priori predictions of cognitive evolutionary hypotheses (i.e., phylogenetic targeting). Here, we explain how an integration of comparative psychology and evolutionary biology will answer a host of questions regarding the phylogenetic distribution and history of cognitive traits, as well as the evolutionary processes that drove their evolution.

  18. On the Discovery of Evolving Truth.

    Science.gov (United States)

    Li, Yaliang; Li, Qi; Gao, Jing; Su, Lu; Zhao, Bo; Fan, Wei; Han, Jiawei

    2015-08-01

    In the era of big data, information regarding the same objects can be collected from increasingly more sources. Unfortunately, there usually exist conflicts among the information coming from different sources. To tackle this challenge, truth discovery, i.e., to integrate multi-source noisy information by estimating the reliability of each source, has emerged as a hot topic. In many real world applications, however, the information may come sequentially, and as a consequence, the truth of objects as well as the reliability of sources may be dynamically evolving. Existing truth discovery methods, unfortunately, cannot handle such scenarios. To address this problem, we investigate the temporal relations among both object truths and source reliability, and propose an incremental truth discovery framework that can dynamically update object truths and source weights upon the arrival of new data. Theoretical analysis is provided to show that the proposed method is guaranteed to converge at a fast rate. The experiments on three real world applications and a set of synthetic data demonstrate the advantages of the proposed method over state-of-the-art truth discovery methods.

  19. Sexual regret: evidence for evolved sex differences.

    Science.gov (United States)

    Galperin, Andrew; Haselton, Martie G; Frederick, David A; Poore, Joshua; von Hippel, William; Buss, David M; Gonzaga, Gian C

    2013-10-01

    Regret and anticipated regret enhance decision quality by helping people avoid making and repeating mistakes. Some of people's most intense regrets concern sexual decisions. We hypothesized evolved sex differences in women's and men's experiences of sexual regret. Because of women's higher obligatory costs of reproduction throughout evolutionary history, we hypothesized that sexual actions, particularly those involving casual sex, would be regretted more intensely by women than by men. In contrast, because missed sexual opportunities historically carried higher reproductive fitness costs for men than for women, we hypothesized that poorly chosen sexual inactions would be regretted more by men than by women. Across three studies (Ns = 200, 395, and 24,230), we tested these hypotheses using free responses, written scenarios, detailed checklists, and Internet sampling to achieve participant diversity, including diversity in sexual orientation. Across all data sources, results supported predicted psychological sex differences and these differences were localized in casual sex contexts. These findings are consistent with the notion that the psychology of sexual regret was shaped by recurrent sex differences in selection pressures operating over deep time.

  20. Extracting evolving pathologies via spectral clustering.

    Science.gov (United States)

    Bernardis, Elena; Pohl, Kilian M; Davatzikos, Christos

    2013-01-01

    A bottleneck in the analysis of longitudinal MR scans with white matter brain lesions is the temporally consistent segmentation of the pathology. We identify pathologies in 3D+t(ime) within a spectral graph clustering framework. Our clustering approach simultaneously segments and tracks the evolving lesions by identifying characteristic image patterns at each time-point and voxel correspondences across time-points. For each 3D image, our method constructs a graph where weights between nodes capture the likeliness of two voxels belonging to the same region. Based on these weights, we then establish rough correspondences between graph nodes at different time-points along estimated pathology evolution directions. We combine the graphs by aligning the weights to a reference time-point, thus integrating temporal information across the 3D images, and formulate the 3D+t segmentation problem as a binary partitioning of this graph. The resulting segmentation is very robust to local intensity fluctuations and yields better results than segmentations generated for each time-point.

  1. Functional Topology of Evolving Urban Drainage Networks

    Science.gov (United States)

    Yang, Soohyun; Paik, Kyungrock; McGrath, Gavan S.; Urich, Christian; Krueger, Elisabeth; Kumar, Praveen; Rao, P. Suresh C.

    2017-11-01

    We investigated the scaling and topology of engineered urban drainage networks (UDNs) in two cities, and further examined UDN evolution over decades. UDN scaling was analyzed using two power law scaling characteristics widely employed for river networks: (1) Hack's law of length (L)-area (A) [L∝Ah] and (2) exceedance probability distribution of upstream contributing area (δ) [P>(A≥δ>)˜aδ-ɛ]. For the smallest UDNs ((A≥δ>) plots for river networks are abruptly truncated, those for UDNs display exponential tempering [P>(A≥δ>)=aδ-ɛexp⁡>(-cδ>)]. The tempering parameter c decreases as the UDNs grow, implying that the distribution evolves in time to resemble those for river networks. However, the power law exponent ɛ for large UDNs tends to be greater than the range reported for river networks. Differences in generative processes and engineering design constraints contribute to observed differences in the evolution of UDNs and river networks, including subnet heterogeneity and nonrandom branching.

  2. The Evolving Classification of Pulmonary Hypertension.

    Science.gov (United States)

    Foshat, Michelle; Boroumand, Nahal

    2017-05-01

    - An explosion of information on pulmonary hypertension has occurred during the past few decades. The perception of this disease has shifted from purely clinical to incorporate new knowledge of the underlying pathology. This transfer has occurred in light of advancements in pathophysiology, histology, and molecular medical diagnostics. - To update readers about the evolving understanding of the etiology and pathogenesis of pulmonary hypertension and to demonstrate how pathology has shaped the current classification. - Information presented at the 5 World Symposia on pulmonary hypertension held since 1973, with the last meeting occurring in 2013, was used in this review. - Pulmonary hypertension represents a heterogeneous group of disorders that are differentiated based on differences in clinical, hemodynamic, and histopathologic features. Early concepts of pulmonary hypertension were largely influenced by pharmacotherapy, hemodynamic function, and clinical presentation of the disease. The initial nomenclature for pulmonary hypertension segregated the clinical classifications from pathologic subtypes. Major restructuring of this disease classification occurred between the first and second symposia, which was the first to unite clinical and pathologic information in the categorization scheme. Additional changes were introduced in subsequent meetings, particularly between the third and fourth World Symposia meetings, when additional pathophysiologic information was gained. Discoveries in molecular diagnostics significantly progressed the understanding of idiopathic pulmonary arterial hypertension. Continued advancements in imaging modalities, mechanistic pathogenicity, and molecular biomarkers will enable physicians to define pulmonary hypertension phenotypes based on the pathobiology and allow for treatment customization.

  3. Evolving application of biomimetic nanostructured hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Norberto Roveri

    2010-11-01

    Full Text Available Norberto Roveri, Michele IafiscoLaboratory of Environmental and Biological Structural Chemistry (LEBSC, Dipartimento di Chimica ‘G. Ciamician’, Alma Mater Studiorum, Università di Bologna, Bologna, ItalyAbstract: By mimicking Nature, we can design and synthesize inorganic smart materials that are reactive to biological tissues. These smart materials can be utilized to design innovative third-generation biomaterials, which are able to not only optimize their interaction with biological tissues and environment, but also mimic biogenic materials in their functionalities. The biomedical applications involve increasing the biomimetic levels from chemical composition, structural organization, morphology, mechanical behavior, nanostructure, and bulk and surface chemical–physical properties until the surface becomes bioreactive and stimulates cellular materials. The chemical–physical characteristics of biogenic hydroxyapatites from bone and tooth have been described, in order to point out the elective sides, which are important to reproduce the design of a new biomimetic synthetic hydroxyapatite. This review outlines the evolving applications of biomimetic synthetic calcium phosphates, details the main characteristics of bone and tooth, where the calcium phosphates are present, and discusses the chemical–physical characteristics of biomimetic calcium phosphates, methods of synthesizing them, and some of their biomedical applications.Keywords: hydroxyapatite, nanocrystals, biomimetism, biomaterials, drug delivery, remineralization

  4. Evolving application of biomimetic nanostructured hydroxyapatite.

    Science.gov (United States)

    Roveri, Norberto; Iafisco, Michele

    2010-11-09

    By mimicking Nature, we can design and synthesize inorganic smart materials that are reactive to biological tissues. These smart materials can be utilized to design innovative third-generation biomaterials, which are able to not only optimize their interaction with biological tissues and environment, but also mimic biogenic materials in their functionalities. The biomedical applications involve increasing the biomimetic levels from chemical composition, structural organization, morphology, mechanical behavior, nanostructure, and bulk and surface chemical-physical properties until the surface becomes bioreactive and stimulates cellular materials. The chemical-physical characteristics of biogenic hydroxyapatites from bone and tooth have been described, in order to point out the elective sides, which are important to reproduce the design of a new biomimetic synthetic hydroxyapatite. This review outlines the evolving applications of biomimetic synthetic calcium phosphates, details the main characteristics of bone and tooth, where the calcium phosphates are present, and discusses the chemical-physical characteristics of biomimetic calcium phosphates, methods of synthesizing them, and some of their biomedical applications.

  5. Epidemic spreading on evolving signed networks

    Science.gov (United States)

    Saeedian, M.; Azimi-Tafreshi, N.; Jafari, G. R.; Kertesz, J.

    2017-02-01

    Most studies of disease spreading consider the underlying social network as obtained without the contagion, though epidemic influences people's willingness to contact others: A "friendly" contact may be turned to "unfriendly" to avoid infection. We study the susceptible-infected disease-spreading model on signed networks, in which each edge is associated with a positive or negative sign representing the friendly or unfriendly relation between its end nodes. In a signed network, according to Heider's theory, edge signs evolve such that finally a state of structural balance is achieved, corresponding to no frustration in physics terms. However, the danger of infection affects the evolution of its edge signs. To describe the coupled problem of the sign evolution and disease spreading, we generalize the notion of structural balance by taking into account the state of the nodes. We introduce an energy function and carry out Monte Carlo simulations on complete networks to test the energy landscape, where we find local minima corresponding to the so-called jammed states. We study the effect of the ratio of initial friendly to unfriendly connections on the propagation of disease. The steady state can be balanced or a jammed state such that a coexistence occurs between susceptible and infected nodes in the system.

  6. Orbital Decay in Binaries with Evolved Stars

    Science.gov (United States)

    Sun, Meng; Arras, Phil; Weinberg, Nevin N.; Troup, Nicholas; Majewski, Steven R.

    2018-01-01

    Two mechanisms are often invoked to explain tidal friction in binary systems. The ``dynamical tide” is the resonant excitation of internal gravity waves by the tide, and their subsequent damping by nonlinear fluid processes or thermal diffusion. The ``equilibrium tide” refers to non-resonant excitation of fluid motion in the star’s convection zone, with damping by interaction with the turbulent eddies. There have been numerous studies of these processes in main sequence stars, but less so on the subgiant and red giant branches. Motivated by the newly discovered close binary systems in the Apache Point Observatory Galactic Evolution Experiment (APOGEE-1), we have performed calculations of both the dynamical and equilibrium tide processes for stars over a range of mass as the star’s cease core hydrogen burning and evolve to shell burning. Even for stars which had a radiative core on the main sequence, the dynamical tide may have very large amplitude in the newly radiative core in post-main sequence, giving rise to wave breaking. The resulting large dynamical tide dissipation rate is compared to the equilibrium tide, and the range of secondary masses and orbital periods over which rapid orbital decay may occur will be discussed, as well as applications to close APOGEE binaries.

  7. UKAEA'S evolving contract philosophy

    Energy Technology Data Exchange (ETDEWEB)

    Nicol, R. D. [UK Atomic Energy Authority, UKAEA, Harwell, Oxfordshire (United Kingdom)

    2003-07-01

    The United Kingdom Atomic Energy Authority (UKAEA) has gone through fundamental change over the last ten years. At the heart of this change has been UKAEA's relationship with the contracting and supply market. This paper describes the way in which UKAEA actively developed the market to support the decommissioning programme, and how the approach to contracting has evolved as external pressures and demands have changed. UKAEA's pro-active approach to industry has greatly assisted the development of a healthy, competitive market for services supporting decommissioning in the UK. There have been difficult changes and many challenges along the way, and some retrenchment was necessary to meet regulatory requirements. Nevertheless, UKAEA has sustained a high level of competition - now measured in terms of competed spend as a proportion of competable spend - with annual out-turns consistently over 80%. The prime responsibility for market development will pass to the new Nuclear Decommissioning Authority (NDA) in 2005, as the owner, on behalf of the Government, of the UK's civil nuclear liabilities. The preparatory work for the NDA indicates that the principles established by UKAEA will be carried forward. (author)

  8. An evolving model of online bipartite networks

    Science.gov (United States)

    Zhang, Chu-Xu; Zhang, Zi-Ke; Liu, Chuang

    2013-12-01

    Understanding the structure and evolution of online bipartite networks is a significant task since they play a crucial role in various e-commerce services nowadays. Recently, various attempts have been tried to propose different models, resulting in either power-law or exponential degree distributions. However, many empirical results show that the user degree distribution actually follows a shifted power-law distribution, the so-called Mandelbrot’s law, which cannot be fully described by previous models. In this paper, we propose an evolving model, considering two different user behaviors: random and preferential attachment. Extensive empirical results on two real bipartite networks, Delicious and CiteULike, show that the theoretical model can well characterize the structure of real networks for both user and object degree distributions. In addition, we introduce a structural parameter p, to demonstrate that the hybrid user behavior leads to the shifted power-law degree distribution, and the region of power-law tail will increase with the increment of p. The proposed model might shed some lights in understanding the underlying laws governing the structure of real online bipartite networks.

  9. Did gene family expansions during the Eocene-Oligocene boundary climate cooling play a role in Pooideae adaptation to cool climates?

    Science.gov (United States)

    Sandve, Simen Rød; Fjellheim, Siri

    2010-05-01

    Adaptation to cool environments is a common feature in the core group of the grass subfamily Pooideae (Triticeae and Poeae). This suggest an ancient evolutionary origin of low temperature stress tolerance dating back prior to the initiation of taxonomic divergence of core Pooideae species. Viewing the Pooideae evolution in a palaeo-climatic perspective reveals that taxonomic divergence of the core Pooideae group initiated shortly after a global super-cooling period at the Eocene-Oligocene boundary (approximately 33.5-26 Ma). This global climate cooling altered distributions of plants and animals and must have imposed selection pressure for improved low temperature stress responses. Lineage-specific gene family expansions are known to be involved in adaptation to new environmental stresses. In Pooideae, two gene families involved in low temperature stress response, the C-repeat binding factor (CBF) and fructosyl transferase (FT) gene families, has undergone lineage-specific expansions. We investigated the timing of these gene family expansions by molecular dating and found that Pooideae-specific expansion events in CBF and FT gene families took place during Eocene-Oligocene super-cooling period. We hypothesize that the E-O super-cooling exerted selection pressure for improved low temperature stress response and frost tolerance in a core Pooideae ancestor, and that those individuals with multiple copies of CBF and FT genes were favoured.

  10. Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser

    Science.gov (United States)

    2010-01-01

    Background Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB), an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1) and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae). Saccharomyces cerevisiae is also included as a reference genome. Results CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine) and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans. Conclusions Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http://cgob.ucd.ie. PMID:20459735

  11. Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser

    Directory of Open Access Journals (Sweden)

    Byrne Kevin P

    2010-05-01

    Full Text Available Abstract Background Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB, an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1 and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae. Saccharomyces cerevisiae is also included as a reference genome. Results CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans. Conclusions Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http://cgob.ucd.ie.

  12. Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser.

    Science.gov (United States)

    Fitzpatrick, David A; O'Gaora, Peadar; Byrne, Kevin P; Butler, Geraldine

    2010-05-10

    Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB), an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1) and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae). Saccharomyces cerevisiae is also included as a reference genome. CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine) and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans. Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http://cgob.ucd.ie.

  13. Analysis of gene evolution and metabolic pathways using the Candida Gene Order Browser

    LENUS (Irish Health Repository)

    Fitzpatrick, David A

    2010-05-10

    Abstract Background Candida species are the most common cause of opportunistic fungal infection worldwide. Recent sequencing efforts have provided a wealth of Candida genomic data. We have developed the Candida Gene Order Browser (CGOB), an online tool that aids comparative syntenic analyses of Candida species. CGOB incorporates all available Candida clade genome sequences including two Candida albicans isolates (SC5314 and WO-1) and 8 closely related species (Candida dubliniensis, Candida tropicalis, Candida parapsilosis, Lodderomyces elongisporus, Debaryomyces hansenii, Pichia stipitis, Candida guilliermondii and Candida lusitaniae). Saccharomyces cerevisiae is also included as a reference genome. Results CGOB assignments of homology were manually curated based on sequence similarity and synteny. In total CGOB includes 65617 genes arranged into 13625 homology columns. We have also generated improved Candida gene sets by merging\\/removing partial genes in each genome. Interrogation of CGOB revealed that the majority of tandemly duplicated genes are under strong purifying selection in all Candida species. We identified clusters of adjacent genes involved in the same metabolic pathways (such as catabolism of biotin, galactose and N-acetyl glucosamine) and we showed that some clusters are species or lineage-specific. We also identified one example of intron gain in C. albicans. Conclusions Our analysis provides an important resource that is now available for the Candida community. CGOB is available at http:\\/\\/cgob.ucd.ie.

  14. Evolution of TWIN SISTER of FT (TSF Genes in Brassicaceae

    Directory of Open Access Journals (Sweden)

    Yunyan Hu

    2016-01-01

    Full Text Available FT and its homolog, TWIN SISTER OF FT (TSF, act redundantly as integrators in floral transition pathways in Arabidopsis thaliana. The evolution of these key flowering regulatory genes during Brassicaceae speciation has not been well studied; therefore, we investigated their evolution in 13 sequenced Brassicaceae species. While the phylogenetic analysis indicated that FT gene evolution has followed two independent lineage-specific routes, TSF evolution does not appear to have been completely consistent within the Brassicaceae lineage I and lineage II division. The two TSF copies in the Thellungiella genus were divided into A and B groups in the phylogenetic analysis. Examination of conserved non-coding sequences and conserved domains within a 5 kb region upstream of the TSF start codon revealed the same group division inferred by the phylogenetic analysis. In addition, TSF genes retained syntenic relationships among genes in the same group, but not between group A and group B. The two copies of the TSF gene in the Thellungiella species were syntenic to the TSF genes in group A and group B, respectively. We also identified TSF-A gene residues in the syntenic region of group B species, but no TSF-B residues could be found in the group A syntenic region. Therefore, we inferred that the TSF genes in lineage II species experienced a duplication event after diversification from lineage I. Following their split from Thellungiella, Brassica species lost the ancestral TSF gene and retained the duplicated copy.

  15. Quantum mechanics in an evolving Hilbert space

    Science.gov (United States)

    Artacho, Emilio; O'Regan, David D.

    2017-03-01

    Many basis sets for electronic structure calculations evolve with varying external parameters, such as moving atoms in dynamic simulations, giving rise to extra derivative terms in the dynamical equations. Here we revisit these derivatives in the context of differential geometry, thereby obtaining a more transparent formalization, and a geometrical perspective for better understanding the resulting equations. The effect of the evolution of the basis set within the spanned Hilbert space separates explicitly from the effect of the turning of the space itself when moving in parameter space, as the tangent space turns when moving in a curved space. New insights are obtained using familiar concepts in that context such as the Riemann curvature. The differential geometry is not strictly that for curved spaces as in general relativity, a more adequate mathematical framework being provided by fiber bundles. The language used here, however, will be restricted to tensors and basic quantum mechanics. The local gauge implied by a smoothly varying basis set readily connects with Berry's formalism for geometric phases. Generalized expressions for the Berry connection and curvature are obtained for a parameter-dependent occupied Hilbert space spanned by nonorthogonal Wannier functions. The formalism is applicable to basis sets made of atomic-like orbitals and also more adaptative moving basis functions (such as in methods using Wannier functions as intermediate or support bases), but should also apply to other situations in which nonorthogonal functions or related projectors should arise. The formalism is applied to the time-dependent quantum evolution of electrons for moving atoms. The geometric insights provided here allow us to propose new finite-difference time integrators, and also better understand those already proposed.

  16. The evolving role of tiotropium in asthma

    Directory of Open Access Journals (Sweden)

    McIvor ER

    2017-08-01

    Full Text Available Emma R McIvor,1 R Andrew McIvor2 1Queen’s University, Belfast, UK; 2Department of Medicine, McMaster University, Firestone Institute for Respiratory Health, Hamilton, Ontario, Canada Abstract: Tiotropium is a long-acting muscarinic antagonist (LAMA that exerts its bronchodilatory effect by blocking endogenous acetylcholine receptors in the airways. Its safety and efficacy are well established for the treatment of COPD, and it is now being recognized for its role in improving lung function and control in asthma. This review discusses the evolving role of tiotropium delivered by the Respimat® in patients across the range of asthma severities and ages, and provides an overview of safety and efficacy data. Tiotropium is the only LAMA currently approved for the treatment of asthma, and evidence from a large-scale clinical trial program, including several Phase III studies in adults, has demonstrated that tiotropium improves lung function and asthma control, with a safety profile comparable with that of placebo. Clinical trials in adolescent patients (aged 12–17 years have also shown improvements in lung function and trends toward improved asthma control. Of note, the efficacy and safety profiles are consistent regardless of baseline characteristics and phenotype. Given the large and growing body of evidence, it is likely that as clinical experience with tiotropium increases, this treatment may possibly emerge as the key choice for add-on therapy to inhaled corticosteroids/long-acting β2-agonists, and in patients who do not tolerate long-acting bronchodilators or other medications, in the future. Keywords: tiotropium, anticholinergics, asthma, efficacy

  17. Emergent spacetime in stochastically evolving dimensions

    Energy Technology Data Exchange (ETDEWEB)

    Afshordi, Niayesh [Perimeter Institute for Theoretical Physics, 31 Caroline St. N., Waterloo, ON, N2L 2Y5 (Canada); Department of Physics and Astronomy, University of Waterloo, Waterloo, ON, N2L 3G1 (Canada); HEPCOS, Department of Physics, SUNY at Buffalo, Buffalo, NY 14260-1500 (United States); Stojkovic, Dejan, E-mail: ds77@buffalo.edu [Perimeter Institute for Theoretical Physics, 31 Caroline St. N., Waterloo, ON, N2L 2Y5 (Canada); HEPCOS, Department of Physics, SUNY at Buffalo, Buffalo, NY 14260-1500 (United States)

    2014-12-12

    Changing the dimensionality of the space–time at the smallest and largest distances has manifold theoretical advantages. If the space is lower dimensional in the high energy regime, then there are no ultraviolet divergencies in field theories, it is possible to quantize gravity, and the theory of matter plus gravity is free of divergencies or renormalizable. If the space is higher dimensional at cosmological scales, then some cosmological problems (including the cosmological constant problem) can be attacked from a completely new perspective. In this paper, we construct an explicit model of “evolving dimensions” in which the dimensions open up as the temperature of the universe drops. We adopt the string theory framework in which the dimensions are fields that live on the string worldsheet, and add temperature dependent mass terms for them. At the Big Bang, all the dimensions are very heavy and are not excited. As the universe cools down, dimensions open up one by one. Thus, the dimensionality of the space we live in depends on the energy or temperature that we are probing. In particular, we provide a kinematic Brandenberger–Vafa argument for how a discrete causal set, and eventually a continuum (3+1)-dim spacetime along with Einstein gravity emerges in the Infrared from the worldsheet action. The (3+1)-dim Planck mass and the string scale become directly related, without any compactification. Amongst other predictions, we argue that LHC might be blind to new physics even if it comes at the TeV scale. In contrast, cosmic ray experiments, especially those that can register the very beginning of the shower, and collisions with high multiplicity and density of particles, might be sensitive to the dimensional cross-over.

  18. Emergent spacetime in stochastically evolving dimensions

    Science.gov (United States)

    Afshordi, Niayesh; Stojkovic, Dejan

    2014-12-01

    Changing the dimensionality of the space-time at the smallest and largest distances has manifold theoretical advantages. If the space is lower dimensional in the high energy regime, then there are no ultraviolet divergencies in field theories, it is possible to quantize gravity, and the theory of matter plus gravity is free of divergencies or renormalizable. If the space is higher dimensional at cosmological scales, then some cosmological problems (including the cosmological constant problem) can be attacked from a completely new perspective. In this paper, we construct an explicit model of ;evolving dimensions; in which the dimensions open up as the temperature of the universe drops. We adopt the string theory framework in which the dimensions are fields that live on the string worldsheet, and add temperature dependent mass terms for them. At the Big Bang, all the dimensions are very heavy and are not excited. As the universe cools down, dimensions open up one by one. Thus, the dimensionality of the space we live in depends on the energy or temperature that we are probing. In particular, we provide a kinematic Brandenberger-Vafa argument for how a discrete causal set, and eventually a continuum (3 + 1)-dim spacetime along with Einstein gravity emerges in the Infrared from the worldsheet action. The (3 + 1)-dim Planck mass and the string scale become directly related, without any compactification. Amongst other predictions, we argue that LHC might be blind to new physics even if it comes at the TeV scale. In contrast, cosmic ray experiments, especially those that can register the very beginning of the shower, and collisions with high multiplicity and density of particles, might be sensitive to the dimensional cross-over.

  19. Emergent spacetime in stochastically evolving dimensions

    Directory of Open Access Journals (Sweden)

    Niayesh Afshordi

    2014-12-01

    Full Text Available Changing the dimensionality of the space–time at the smallest and largest distances has manifold theoretical advantages. If the space is lower dimensional in the high energy regime, then there are no ultraviolet divergencies in field theories, it is possible to quantize gravity, and the theory of matter plus gravity is free of divergencies or renormalizable. If the space is higher dimensional at cosmological scales, then some cosmological problems (including the cosmological constant problem can be attacked from a completely new perspective. In this paper, we construct an explicit model of “evolving dimensions” in which the dimensions open up as the temperature of the universe drops. We adopt the string theory framework in which the dimensions are fields that live on the string worldsheet, and add temperature dependent mass terms for them. At the Big Bang, all the dimensions are very heavy and are not excited. As the universe cools down, dimensions open up one by one. Thus, the dimensionality of the space we live in depends on the energy or temperature that we are probing. In particular, we provide a kinematic Brandenberger–Vafa argument for how a discrete causal set, and eventually a continuum (3+1-dim spacetime along with Einstein gravity emerges in the Infrared from the worldsheet action. The (3+1-dim Planck mass and the string scale become directly related, without any compactification. Amongst other predictions, we argue that LHC might be blind to new physics even if it comes at the TeV scale. In contrast, cosmic ray experiments, especially those that can register the very beginning of the shower, and collisions with high multiplicity and density of particles, might be sensitive to the dimensional cross-over.

  20. Evolvable Cryogenics (ECRYO) Pressure Transducer Calibration Test

    Science.gov (United States)

    Diaz, Carlos E., Jr.

    2015-01-01

    This paper provides a summary of the findings of recent activities conducted by Marshall Space Flight Center's (MSFC) In-Space Propulsion Branch and MSFC's Metrology and Calibration Lab to assess the performance of current "state of the art" pressure transducers for use in long duration storage and transfer of cryogenic propellants. A brief historical narrative in this paper describes the Evolvable Cryogenics program and the relevance of these activities to the program. This paper also provides a review of three separate test activities performed throughout this effort, including: (1) the calibration of several pressure transducer designs in a liquid nitrogen cryogenic environmental chamber, (2) the calibration of a pressure transducer in a liquid helium Dewar, and (3) the calibration of several pressure transducers at temperatures ranging from 20 to 70 degrees Kelvin (K) using a "cryostat" environmental chamber. These three separate test activities allowed for study of the sensors along a temperature range from 4 to 300 K. The combined data shows that both the slope and intercept of the sensor's calibration curve vary as a function of temperature. This homogeneous function is contrary to the linearly decreasing relationship assumed at the start of this investigation. Consequently, the data demonstrates the need for lookup tables to change the slope and intercept used by any data acquisition system. This ultimately would allow for more accurate pressure measurements at the desired temperature range. This paper concludes with a review of a request for information (RFI) survey conducted amongst different suppliers to determine the availability of current "state of the art" flight-qualified pressure transducers. The survey identifies requirements that are most difficult for the suppliers to meet, most notably the capability to validate the sensor's performance at temperatures below 70 K.

  1. Evolving Concepts and Translational Relevance of Enteroendocrine Cell Biology.

    Science.gov (United States)

    Drucker, Daniel J

    2016-03-01

    Classical enteroenteroendocrine cell (EEC) biology evolved historically from identification of scattered hormone-producing endocrine cells within the epithelial mucosa of the stomach, small and large intestine. Purification of functional EEC hormones from intestinal extracts, coupled with molecular cloning of cDNAs and genes expressed within EECs has greatly expanded the complexity of EEC endocrinology, with implications for understanding the contribution of EECs to disease pathophysiology. Pubmed searches identified manuscripts highlighting new concepts illuminating the molecular biology, classification and functional role(s) of EECs and their hormonal products. Molecular interrogation of EECs has been transformed over the past decade, raising multiple new questions that challenge historical concepts of EEC biology. Evidence for evolution of the EEC from a unihormonal cell type with classical endocrine actions, to a complex plurihormonal dynamic cell with pleiotropic interactive functional networks within the gastrointestinal mucosa is critically assessed. We discuss gaps in understanding how EECs sense and respond to nutrients, cytokines, toxins, pathogens, the microbiota, and the microbial metabolome, and highlight the expanding translational relevance of EECs in the pathophysiology and therapy of metabolic and inflammatory disorders. The EEC system represents the largest specialized endocrine network in human physiology, integrating environmental and nutrient cues, enabling neural and hormonal control of metabolic homeostasis. Updating EEC classification systems will enable more accurate comparative analyses of EEC subpopulations and endocrine networks in multiple regions of the gastrointestinal tract.

  2. Pangenome evidence for extensive interdomain horizontal transfer affecting lineage core and shell genes in uncultured planktonic thaumarchaeota and euryarchaeota.

    Science.gov (United States)

    Deschamps, Philippe; Zivanovic, Yvan; Moreira, David; Rodriguez-Valera, Francisco; López-García, Purificación

    2014-06-12

    Horizontal gene transfer (HGT) is an important force in evolution, which may lead, among other things, to the adaptation to new environments by the import of new metabolic functions. Recent studies based on phylogenetic analyses of a few genome fragments containing archaeal 16S rRNA genes and fosmid-end sequences from deep-sea metagenomic libraries have suggested that marine planktonic archaea could be affected by high HGT frequency. Likewise, a composite genome of an uncultured marine euryarchaeote showed high levels of gene sequence similarity to bacterial genes. In this work, we ask whether HGT is frequent and widespread in genomes of these marine archaea, and whether HGT is an ancient and/or recurrent phenomenon. To answer these questions, we sequenced 997 fosmid archaeal clones from metagenomic libraries of deep-Mediterranean waters (1,000 and 3,000 m depth) and built comprehensive pangenomes for planktonic Thaumarchaeota (Group I archaea) and Euryarchaeota belonging to the uncultured Groups II and III Euryarchaeota (GII/III-Euryarchaeota). Comparison with available reference genomes of Thaumarchaeota and a composite marine surface euryarchaeote genome allowed us to define sets of core, lineage-specific core, and shell gene ortholog clusters for the two archaeal lineages. Molecular phylogenetic analyses of all gene clusters showed that 23.9% of marine Thaumarchaeota genes and 29.7% of GII/III-Euryarchaeota genes had been horizontally acquired from bacteria. HGT is not only extensive and directional but also ongoing, with high HGT levels in lineage-specific core (ancient transfers) and shell (recent transfers) genes. Many of the acquired genes are related to metabolism and membrane biogenesis, suggesting an adaptive value for life in cold, oligotrophic oceans. We hypothesize that the acquisition of an important amount of foreign genes by the ancestors of these archaeal groups significantly contributed to their divergence and ecological success. © The Author

  3. Orthogonally Evolved AI to Improve Difficulty Adjustment in Video Games

    DEFF Research Database (Denmark)

    Hintze, Arend; Olson, Randal; Lehman, Joel Anthony

    2016-01-01

    (i.e. agents subject to fewer generations of evolution) make for easier opponents, while highly-evolved agents are more challenging to overcome. In this publication we test a new approach for difficulty adjustment in games: orthogonally evolved AI, where the player receives support from collaborating...... opponents. Furthermore, human interaction can modulate (and be informed by) the performance and behavior of collaborating agents. In this way, orthogonally evolved AI both facilitates smoother difficulty adjustment and enables new game experiences....

  4. Evolving R Coronae Borealis Stars with MESA

    Science.gov (United States)

    Clayton, Geoffrey C.; Lauer, Amber; Chatzopoulos, Emmanouil; Frank, Juhan

    2018-01-01

    being a WD. Solving the mystery of how the RCB stars evolve will lead to a better understanding of other important types of stellar merger events such as Type Ia SNe.

  5. Gastrointestinal Stromal Tumor – An Evolving Concept

    Science.gov (United States)

    Tornillo, Luigi

    2014-01-01

    Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. The discovery that these tumors, formerly thought of smooth muscle origin, are indeed better characterized by specific activating mutation in genes coding for the receptor tyrosine kinases (RTKs) CKIT and PDGFRA and that these mutations are strongly predictive for the response to targeted therapy with RTK inhibitors has made GISTs the typical example of the integration of basic molecular knowledge in the daily clinical activity. The information on the mutational status of these tumors is essential to predict (and subsequently to plan) the therapy. As resistant cases are frequently wild type, other possible oncogenic events, defining other “entities,” have been discovered (e.g., succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, and mutations in the RAS-RAF-MAPK pathway). The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data. PMID:25593916

  6. Gastrointestinal stromal tumor - an evolving concept.

    Science.gov (United States)

    Tornillo, Luigi

    2014-01-01

    Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. The discovery that these tumors, formerly thought of smooth muscle origin, are indeed better characterized by specific activating mutation in genes coding for the receptor tyrosine kinases (RTKs) CKIT and PDGFRA and that these mutations are strongly predictive for the response to targeted therapy with RTK inhibitors has made GISTs the typical example of the integration of basic molecular knowledge in the daily clinical activity. The information on the mutational status of these tumors is essential to predict (and subsequently to plan) the therapy. As resistant cases are frequently wild type, other possible oncogenic events, defining other "entities," have been discovered (e.g., succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, and mutations in the RAS-RAF-MAPK pathway). The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data.

  7. Ancestral and derived attributes of the dlx gene repertoire, cluster structure and expression patterns in an African cichlid fish

    Directory of Open Access Journals (Sweden)

    Renz Adina J

    2011-01-01

    Full Text Available Abstract Background Cichlid fishes have undergone rapid, expansive evolutionary radiations that are manifested in the diversification of their trophic morphologies, tooth patterning and coloration. Understanding the molecular mechanisms that underlie the cichlids' unique patterns of evolution requires a thorough examination of genes that pattern the neural crest, from which these diverse phenotypes are derived. Among those genes, the homeobox-containing Dlx gene family is of particular interest since it is involved in the patterning of the brain, jaws and teeth. Results In this study, we characterized the dlx genes of an African cichlid fish, Astatotilapia burtoni, to provide a baseline to later allow cross-species comparison within Cichlidae. We identified seven dlx paralogs (dlx1a, -2a, -4a, -3b, -4b, -5a and -6a, whose orthologies were validated with molecular phylogenetic trees. The intergenic regions of three dlx gene clusters (dlx1a-2a, dlx3b-4b, and dlx5a-6a were amplified with long PCR. Intensive cross-species comparison revealed a number of conserved non-coding elements (CNEs that are shared with other percomorph fishes. This analysis highlighted additional lineage-specific gains/losses of CNEs in different teleost fish lineages and a novel CNE that had previously not been identified. Our gene expression analyses revealed overlapping but distinct expression of dlx orthologs in the developing brain and pharyngeal arches. Notably, four of the seven A. burtoni dlx genes, dlx2a, dlx3b, dlx4a and dlx5a, were expressed in the developing pharyngeal teeth. Conclusion This comparative study of the dlx genes of A. burtoni has deepened our knowledge of the diversity of the Dlx gene family, in terms of gene repertoire, expression patterns and non-coding elements. We have identified possible cichlid lineage-specific changes, including losses of a subset of dlx expression domains in the pharyngeal teeth, which will be the targets of future functional

  8. Gene family expansions and contractions are associated with host range in plant pathogens of the genus Colletotrichum.

    Science.gov (United States)

    Baroncelli, Riccardo; Amby, Daniel Buchvaldt; Zapparata, Antonio; Sarrocco, Sabrina; Vannacci, Giovanni; Le Floch, Gaétan; Harrison, Richard J; Holub, Eric; Sukno, Serenella A; Sreenivasaprasad, Surapareddy; Thon, Michael R

    2016-08-05

    Many species belonging to the genus Colletotrichum cause anthracnose disease on a wide range of plant species. In addition to their economic impact, the genus Colletotrichum is a useful model for the study of the evolution of host specificity, speciation and reproductive behaviors. Genome projects of Colletotrichum species have already opened a new era for studying the evolution of pathogenesis in fungi. We sequenced and annotated the genomes of four strains in the Colletotrichum acutatum species complex (CAsc), a clade of broad host range pathogens within the genus. The four CAsc proteomes and secretomes along with those representing an additional 13 species (six Colletotrichum spp. and seven other Sordariomycetes) were classified into protein families using a variety of tools. Hierarchical clustering of gene family and functional domain assignments, and phylogenetic analyses revealed lineage specific losses of carbohydrate-active enzymes (CAZymes) and proteases encoding genes in Colletotrichum species that have narrow host range as well as duplications of these families in the CAsc. We also found a lineage specific expansion of necrosis and ethylene-inducing peptide 1 (Nep1)-like protein (NLPs) families within the CAsc. This study illustrates the plasticity of Colletotrichum genomes, and shows that major changes in host range are associated with relatively recent changes in gene content.

  9. Network Centrality Analysis in Fungi Reveals Complex Regulation of Lost and Gained Genes.

    Science.gov (United States)

    Coulombe-Huntington, Jasmin; Xia, Yu

    2017-01-01

    Gene gain and loss shape both proteomes and the networks they form. The increasing availability of closely related sequenced genomes and of genome-wide network data should enable a better understanding of the evolutionary forces driving gene gain, gene loss and evolutionary network rewiring. Using orthology mappings across 23 ascomycete fungi genomes, we identified proteins that were lost, gained or universally conserved across the tree, enabling us to compare genes across all stages of their life-cycle. Based on a collection of genome-wide network and gene expression datasets from baker's yeast, as well as a few from fission yeast, we found that gene loss is more strongly associated with network and expression features of closely related species than that of distant species, consistent with the evolutionary modulation of gene loss propensity through network rewiring. We also discovered that lost and gained genes, as compared to universally conserved "core" genes, have more regulators, more complex expression patterns and are much more likely to encode for transcription factors. Finally, we found that the relative rate of network integration of new genes into the different types of networks agrees with experimentally measured rates of network rewiring. This systems-level view of the life-cycle of eukaryotic genes suggests that the gain and loss of genes is tightly coupled to the gain and loss of network interactions, that lineage-specific adaptations drive regulatory complexity and that the relative rates of integration of new genes are consistent with network rewiring rates.

  10. Loops and autonomy promote evolvability of ecosystem networks.

    Science.gov (United States)

    Luo, Jianxi

    2014-09-29

    The structure of ecological networks, in particular food webs, determines their ability to evolve further, i.e. evolvability. The knowledge about how food web evolvability is determined by the structures of diverse ecological networks can guide human interventions purposefully to either promote or limit evolvability of ecosystems. However, the focus of prior food web studies was on stability and robustness; little is known regarding the impact of ecological network structures on their evolvability. To correlate ecosystem structure and evolvability, we adopt the NK model originally from evolutionary biology to generate and assess the ruggedness of fitness landscapes of a wide spectrum of model food webs with gradual variation in the amount of feeding loops and link density. The variation in network structures is controlled by linkage rewiring. Our results show that more feeding loops and lower trophic link density, i.e. higher autonomy of species, of food webs increase the potential for the ecosystem to generate heritable variations with improved fitness. Our findings allow the prediction of the evolvability of actual food webs according to their network structures, and provide guidance to enhancing or controlling the evolvability of specific ecosystems.

  11. Protein structural modularity and robustness are associated with evolvability.

    Science.gov (United States)

    Rorick, Mary M; Wagner, Günter P

    2011-01-01

    Theory suggests that biological modularity and robustness allow for maintenance of fitness under mutational change, and when this change is adaptive, for evolvability. Empirical demonstrations that these traits promote evolvability in nature remain scant however. This is in part because modularity, robustness, and evolvability are difficult to define and measure in real biological systems. Here, we address whether structural modularity and/or robustness confer evolvability at the level of proteins by looking for associations between indices of protein structural modularity, structural robustness, and evolvability. We propose a novel index for protein structural modularity: the number of regular secondary structure elements (helices and strands) divided by the number of residues in the structure. We index protein evolvability as the proportion of sites with evidence of being under positive selection multiplied by the average rate of adaptive evolution at these sites, and we measure this as an average over a phylogeny of 25 mammalian species. We use contact density as an index of protein designability, and thus, structural robustness. We find that protein evolvability is positively associated with structural modularity as well as structural robustness and that the effect of structural modularity on evolvability is independent of the structural robustness index. We interpret these associations to be the result of reduced constraints on amino acid substitutions in highly modular and robust protein structures, which results in faster adaptation through natural selection.

  12. RNA Structural Analysis by Evolving SHAPE Chemistry

    Science.gov (United States)

    Spitale, Robert C.; Flynn, Ryan A.; Torre, Eduardo A.; Kool, Eric T.; Chang, Howard Y.

    2017-01-01

    RNA is central to the flow of biological information. From transcription to splicing, RNA localization, translation, and decay, RNA is intimately involved in regulating every step of the gene expression program, and is thus essential for health and understanding disease. RNA has the unique ability to base-pair with itself and other nucleic acids to form complex structures. Hence the information content in RNA is not simply its linear sequence of bases, but is also encoded in complex folding of RNA molecules. A general chemical functionality that all RNAs have is a 2’-hydroxyl group in the ribose ring, and the reactivity of the 2'-hydroxyl in RNA is gated by local nucleotide flexibility. In other words, the 2'-hydroxyl is reactive at single-stranded and conformationally flexible positions but is unreactive at nucleotides constrained by base pairing. Recent efforts have been focused on developing reagents that modify RNA as a function of RNA 2’ hydroxyl group flexibility. Such RNA structure probing techniques can be read out by primer extension in experiments termed RNA SHAPE (Selective 2’ Hydroxyl Acylation and Primer Extension). Herein we describe the efforts devoted to the design and utilization of SHAPE probes for characterizing RNA structure. We also describe current technological advances that are being used to utilize SHAPE chemistry with deep sequencing to probe many RNAs in parallel. The merger of chemistry with genomics is sure to open the door to genome-wide exploration of RNA structure and function. PMID:25132067

  13. Microbiota and diabetes: an evolving relationship.

    Science.gov (United States)

    Tilg, Herbert; Moschen, Alexander R

    2014-09-01

    The gut microbiota affects numerous biological functions throughout the body and its characterisation has become a major research area in biomedicine. Recent studies have suggested that gut bacteria play a fundamental role in diseases such as obesity, diabetes and cardiovascular disease. Data are accumulating in animal models and humans suggesting that obesity and type 2 diabetes (T2D) are associated with a profound dysbiosis. First human metagenome-wide association studies demonstrated highly significant correlations of specific intestinal bacteria, certain bacterial genes and respective metabolic pathways with T2D. Importantly, especially butyrate-producing bacteria such as Roseburia intestinalis and Faecalibacterium prausnitzii concentrations were lower in T2D subjects. This supports the increasing evidence, that butyrate and other short-chain fatty acids are able to exert profound immunometabolic effects. Endotoxaemia, most likely gut-derived has also been observed in patients with metabolic syndrome and T2D and might play a key role in metabolic inflammation. A further hint towards an association between microbiota and T2D has been derived from studies in pregnancy showing that major gut microbial shifts occurring during pregnancy affect host metabolism. Interestingly, certain antidiabetic drugs such as metformin also interfere with the intestinal microbiota. Specific members of the microbiota such as Akkermansia muciniphila might be decreased in diabetes and when administered to murines exerted antidiabetic effects. Therefore, as a 'gut signature' becomes more evident in T2D, a better understanding of the role of the microbiota in diabetes might provide new aspects regarding its pathophysiological relevance and pave the way for new therapeutic principles. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Evolving science enhanced with iPS

    Directory of Open Access Journals (Sweden)

    Editor

    2007-11-01

    Full Text Available Dear friends, Greetings from all in the team. With the stage set for online submissions and the review-response-revision-resubmission process standardized, we have come with the first regular issue and from now there will be quarterly issues of the journal. Since the starting of the JSRM in a short span there have been a lot of developments, which we would rather say as "evolutions" keeping in mind, the recent iPS! This evolution we would like you to see from a background of the various developments in the art and science of medicine throughout in the past three centuries. We have come across the era of investigative tools such as bamboo made laryngoscopes to era of vaccines and antibiotics followed by the era of revolutionary non-invasive procedures and recently the nano technology based drugs and now the iPS! Macro to Micro, but still more to go. All through the influence of the society, religions, philosophies have been playing a very important role in every step the science of biology moves ahead. Starting with the contraception, assisted reproduction then the gene modified plants....and now the embryonic stem cells! With the advent of the iPS, though the issues of oncogenes, teratoma yet to be ruled out, we have found there is a way which can bypass the ES cells! Hats off to those scientists who have burnt their midnight oil to have found this way out! The lesson we learn is to explore things with an open mind and continue to proceed further without spending much time fingers crossed. Yours sincerely,The Editorial team.

  15. Diverse CRISPRs evolving in human microbiomes.

    Directory of Open Access Journals (Sweden)

    Mina Rho

    Full Text Available CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats loci, together with cas (CRISPR-associated genes, form the CRISPR/Cas adaptive immune system, a primary defense strategy that eubacteria and archaea mobilize against foreign nucleic acids, including phages and conjugative plasmids. Short spacer sequences separated by the repeats are derived from foreign DNA and direct interference to future infections. The availability of hundreds of shotgun metagenomic datasets from the Human Microbiome Project (HMP enables us to explore the distribution and diversity of known CRISPRs in human-associated microbial communities and to discover new CRISPRs. We propose a targeted assembly strategy to reconstruct CRISPR arrays, which whole-metagenome assemblies fail to identify. For each known CRISPR type (identified from reference genomes, we use its direct repeat consensus sequence to recruit reads from each HMP dataset and then assemble the recruited reads into CRISPR loci; the unique spacer sequences can then be extracted for analysis. We also identified novel CRISPRs or new CRISPR variants in contigs from whole-metagenome assemblies and used targeted assembly to more comprehensively identify these CRISPRs across samples. We observed that the distributions of CRISPRs (including 64 known and 86 novel ones are largely body-site specific. We provide detailed analysis of several CRISPR loci, including novel CRISPRs. For example, known streptococcal CRISPRs were identified in most oral microbiomes, totaling ∼8,000 unique spacers: samples resampled from the same individual and oral site shared the most spacers; different oral sites from the same individual shared significantly fewer, while different individuals had almost no common spacers, indicating the impact of subtle niche differences on the evolution of CRISPR defenses. We further demonstrate potential applications of CRISPRs to the tracing of rare species and the virus exposure of individuals

  16. NASA's Space Launch System: An Evolving Capability for Exploration An Evolving Capability for Exploration

    Science.gov (United States)

    Creech, Stephen D.; Crumbly, Christopher M.; Robinson, Kimerly F.

    2016-01-01

    A foundational capability for international human deep-space exploration, NASA's Space Launch System (SLS) vehicle represents a new spaceflight infrastructure asset, creating opportunities for mission profiles and space systems that cannot currently be executed. While the primary purpose of SLS, which is making rapid progress towards initial launch readiness in two years, will be to support NASA's Journey to Mars, discussions are already well underway regarding other potential utilization of the vehicle's unique capabilities. In its initial Block 1 configuration, capable of launching 70 metric tons (t) to low Earth orbit (LEO), SLS is capable of propelling the Orion crew vehicle to cislunar space, while also delivering small CubeSat-class spacecraft to deep-space destinations. With the addition of a more powerful upper stage, the Block 1B configuration of SLS will be able to deliver 105 t to LEO and enable more ambitious human missions into the proving ground of space. This configuration offers opportunities for launching co-manifested payloads with the Orion crew vehicle, and a class of secondary payloads, larger than today's CubeSats. Further upgrades to the vehicle, including advanced boosters, will evolve its performance to 130 t in its Block 2 configuration. Both Block 1B and Block 2 also offer the capability to carry 8.4- or 10-m payload fairings, larger than any contemporary launch vehicle. With unmatched mass-lift capability, payload volume, and C3, SLS not only enables spacecraft or mission designs currently impossible with contemporary EELVs, it also offers enhancing benefits, such as reduced risk, operational costs and/or complexity, shorter transit time to destination or launching large systems either monolithically or in fewer components. This paper will discuss both the performance and capabilities of Space Launch System as it evolves, and the current state of SLS utilization planning.

  17. Differential gene transfers and gene duplications in primary and secondary endosymbioses

    Directory of Open Access Journals (Sweden)

    McFadden Geoffrey I

    2006-04-01

    Full Text Available Abstract Background Most genes introduced into phototrophic eukaryotes during the process of endosymbiosis are either lost or relocated into the host nuclear genome. In contrast, groEL homologues are found in different genome compartments among phototrophic eukaryotes. Comparative sequence analyses of recently available genome data, have allowed us to reconstruct the evolutionary history of these genes and propose a hypothesis that explains the unusual genome distribution of groEL homologues. Results Our analyses indicate that while two distinct groEL genes were introduced into eukaryotes by a progenitor of plastids, these particular homologues have not been maintained in all evolutionary lineages. This is of significant interest, because two chaperone proteins always co-occur in oxygenic photosynthetic organisms. We infer strikingly different lineage specific processes of evolution involving deletion, duplication and targeting of groEL proteins. Conclusion The requirement of two groEL homologues for chaperon function in phototrophs has provided a constraint that has shaped convergent evolutionary scenarios in divergent evolutionary lineages. GroEL provides a general evolutionary model for studying gene transfers and convergent evolutionary processes among eukaryotic lineages.

  18. Lineage-specific variations in the trigger loop modulate RNA proofreading by bacterial RNA polymerases.

    Science.gov (United States)

    Esyunina, Daria; Turtola, Matti; Pupov, Danil; Bass, Irina; Klimašauskas, Saulius; Belogurov, Georgiy; Kulbachinskiy, Andrey

    2016-02-18

    RNA cleavage by bacterial RNA polymerase (RNAP) has been implicated in transcriptional proofreading and reactivation of arrested transcription elongation complexes but its molecular mechanism is less understood than the mechanism of nucleotide addition, despite both reactions taking place in the same active site. RNAP from the radioresistant bacterium Deinococcus radiodurans is characterized by highly efficient intrinsic RNA cleavage in comparison with Escherichia coli RNAP. We find that the enhanced RNA cleavage activity largely derives from amino acid substitutions in the trigger loop (TL), a mobile element of the active site involved in various RNAP activities. The differences in RNA cleavage between these RNAPs disappear when the TL is deleted, or in the presence of GreA cleavage factors, which replace the TL in the active site. We propose that the TL substitutions modulate the RNA cleavage activity by altering the TL folding and its contacts with substrate RNA and that the resulting differences in transcriptional proofreading may play a role in bacterial stress adaptation. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Phyletic distribution and lineage-specific domain architectures of archaeal two-component signal transduction systems.

    Science.gov (United States)

    Galperin, Michael Y; Makarova, Kira S; Wolf, Yuri I; Koonin, Eugene V

    2017-12-20

    The two-component signal transduction (TCS) machinery is a key mechanism of sensing environmental changes in the prokaryotic world. The TCS systems have been thoroughly characterized in bacteria but to a much lesser extent, in archaea. Here, we provide an updated census of more than 2,000 histidine kinases and response regulators encoded in 218 complete archaeal genomes as well as unfinished genomes available from metagenomic data. We describe the domain architectures of the archaeal TCS components, including several novel output domains, and discuss the evolution of the archaeal TCS machinery. The distribution of TCS systems in archaea is strongly biased, with a high abundance in haloarchaea and thaumarchaea but none detected in the sequenced genomes from the phyla Crenarchaeota, Nanoarchaeota or Korarchaeota. The archaeal sensor histidine kinases are generally similar to their well-studied bacterial counterparts but often located in the cytoplasm and carry multiple PAS and/or GAF domains. In contrast, archaeal response regulators dramatically differ from the bacterial ones. Most archaeal genomes do not encode any of the major classes of bacterial response regulators, such as the DNA-binding transcriptional regulators of the OmpR/PhoB, NarL/FixJ, NtrC, AgrA/LytR, and ActR/PrrA families and the response regulators with GGDEF and/or EAL output domains. Instead, archaea encode multiple copies of response regulators containing either the stand-alone receiver (REC) domain or combinations of REC with PAS and/or GAF domains. Therefore, the prevailing mechanism of archaeal TCS signaling appears to be via a variety of protein-protein interactions, rather than direct transcriptional regulation.IMPORTANCE Although archaea represent a separate domain of life, their signaling systems have been assumed to be closely similar to the bacterial ones. A study of the domain architectures of the archaeal two-component signal transduction (TCS) machinery revealed an overall similarity of archaeal and bacterial sensory modules but substantial differences in the signal output modules. The prevailing mechanism of archaeal TCS signaling appears to involve various protein-protein interactions rather than direct transcription regulation. The complete list of histidine kinases and response regulators encoded in the analyzed archaeal genomes is available online at http://www.ncbi.nlm.nih.gov/Complete_Genomes/TCSarchaea.html. Copyright © 2017 Galperin et al.

  20. Lineage-specific activities of a multipotent mitochondrion of trypanosomatid flagellates.

    Science.gov (United States)

    Škodová-Sveráková, Ingrid; Verner, Zdeněk; Skalický, Tomáš; Votýpka, Jan; Horváth, Anton; Lukeš, Julius

    2015-04-01

    Trypanosomatids are a very diverse group composed of monoxenous and dixenous parasites belonging to the excavate class Kinetoplastea. Here we studied the respiration of five monoxenous species (Blechomonas ayalai, Herpetomonas muscarum, H. samuelpessoai, Leptomonas pyrrhocoris and Sergeia podlipaevi) introduced into culture, each representing a novel yet globally distributed and/or species-rich clade, and compare them with well-studied flagellates Trypanosoma brucei, Phytomonas serpens, Crithidia fasciculata and Leishmania tarentolae. Differences in structure and activities of respiratory chain complexes, respiration and other biochemical parameters recorded under laboratory conditions reveal their substantial diversity, likely a reflection of different host environments. Phylogenetic relationships of the analysed trypanosomatids do not correlate with their biochemical parameters, with the differences within clades by far exceeding those among clades. As the S. podlipaevi canonical respiratory chain complexes have very low activities, we believe that its mitochondrion is utilised for purposes other than oxidative phosphorylation. Hence, the single reticulated mitochondrion of diverse trypanosomatids seems to retain multipotency, with the capacity to activate its individual components based on the host environment. © 2014 John Wiley & Sons Ltd.

  1. Concise review: chemical approaches for modulating lineage-specific stem cells and progenitors.

    Science.gov (United States)

    Xu, Tao; Zhang, Mingliang; Laurent, Timothy; Xie, Min; Ding, Sheng

    2013-05-01

    Generation and manipulation of lineage-restricted stem and progenitor cells in vitro and/or in vivo are critical for the development of stem cell-based clinical therapeutics. Lineage-restricted stem and progenitor cells have many advantageous qualities, including being able to efficiently engraft and differentiate into desirable cell types in vivo after transplantation, and they are much less tumorigenic than pluripotent cells. Generation of lineage-restricted stem and progenitor cells can be achieved by directed differentiation from pluripotent stem cells or lineage conversion from easily obtained somatic cells. Small molecules can be very helpful in these processes since they offer several important benefits. For example, the risk of tumorigenesis is greatly reduced when small molecules are used to replace integrated transcription factors, which are widely used in cell fate conversion. Furthermore, small molecules are relatively easy to apply, optimize, and manufacture, and they can more readily be developed into conventional pharmaceuticals. Alternatively, small molecules can be used to expand or selectively control the differentiation of lineage-restricted stem and progenitor cells for desirable therapeutics purposes in vitro or in vivo. Here we summarize recent progress in the use of small molecules for the expansion and generation of desirable lineage-restricted stem and progenitor cells in vitro and for selectively controlling cell fate of lineage-restricted stem and progenitor cells in vivo, thereby facilitating stem cell-based clinical applications.

  2. Dual lineage-specific expression of Sox17 during mouse embryogenesis

    DEFF Research Database (Denmark)

    Choi, Eunyoung; Kraus, Marine R C; Lemaire, Laurence A

    2012-01-01

    Sox17 is essential for both endoderm development and fetal hematopoietic stem cell (HSC) maintenance. While endoderm-derived organs are well known to originate from Sox17-expressing cells, it is less certain whether fetal HSCs also originate from Sox17-expressing cells. By generating a Sox17(GFPCre......) allele and using it to assess the fate of Sox17-expressing cells during embryogenesis, we confirmed that both endodermal and a part of definitive hematopoietic cells are derived from Sox17-positive cells. Prior to E9.5, the expression of Sox17 is restricted to the endoderm lineage. However, at E9.5 Sox17...... is expressed in the endothelial cells (ECs) at the para-aortic splanchnopleural region that contribute to the formation of HSCs at a later stage. The identification of two distinct progenitor cell populations that express Sox17 at E9.5 was confirmed using fluorescence-activated cell sorting together with RNA...

  3. Lineage-Specific Metabolic Properties and Vulnerabilities of T Cells in the Demyelinating Central Nervous System.

    Science.gov (United States)

    Seki, Scott M; Stevenson, Max; Rosen, Abagail M; Arandjelovic, Sanja; Gemta, Lelisa; Bullock, Timothy N J; Gaultier, Alban

    2017-06-15

    Multiple sclerosis (MS) is a disease that is characterized by immune-mediated destruction of CNS myelin. Current MS therapies aim to block peripheral immune cells from entering the CNS. Although these treatments limit new inflammatory activity in the CNS, no treatment effectively prevents long-term disease progression and disability accumulation in MS patients. One explanation for this paradox is that current therapies are ineffective at targeting immune responses already present in the CNS. To this end, we sought to understand the metabolic properties of T cells that mediate ongoing inflammation in the demyelinating CNS. Using experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a well-studied model of MS, we showed that the CD4(+) and CD8(+) T cells that invade the EAE CNS are highly glycolytic. Elevated glycolytic rates in T cells isolated from the EAE CNS correlate with upregulated expression of glycolytic machinery and is essential for inflammatory responses to myelin. Surprisingly, we found that an inhibitor of GAPDH, 3-bromopyruvic acid (3-BrPa), blocks IFN-γ, but not IL-17A, production in immune cells isolated from the EAE CNS. Indeed, in vitro studies confirmed that the production of IFN-γ by differentiated Th1 cells is more sensitive to 3-BrPa than is the production of IL-17A by Th17 cells. Finally, in transfer models of EAE, 3-BrPa robustly attenuates the encephalitogenic potential of EAE-driving immune cells. To our knowledge, these data are among the first to demonstrate the metabolic properties of T cells in the demyelinating CNS in vivo. Copyright © 2017 by The American Association of Immunologists, Inc.

  4. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

    DEFF Research Database (Denmark)

    Lasko, Loren M; Jakob, Clarissa G; Edalji, Rohinton P

    2017-01-01

    , selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage...... also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent...... model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases....

  5. Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity.

    Directory of Open Access Journals (Sweden)

    Kasum Azim

    2017-03-01

    Full Text Available Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells originating from the SVZ. Next, we used a novel in silico genomic analysis, searchable platform-independent expression database/connectivity map (SPIED/CMAP, to generate a catalogue of small molecules that can be used to manipulate SVZ microdomain-specific lineages. Finally, we demonstrate that compounds identified in this analysis promote the generation of specific cell lineages from NSCs in vivo, during postnatal life and adulthood, as well as in regenerative contexts. This study unravels new strategies for using small bioactive molecules to direct germinal activity in the SVZ, which has therapeutic potential in neurodegenerative diseases.

  6. Screening and discovery of lineage-specific mitosomal membrane proteins in Entamoeba histolytica.

    Science.gov (United States)

    Santos, Herbert J; Imai, Kenichiro; Hanadate, Yuki; Fukasawa, Yoshinori; Oda, Toshiyuki; Mi-Ichi, Fumika; Nozaki, Tomoyoshi

    Entamoeba histolytica, an anaerobic intestinal parasite causing dysentery and extra-intestinal abscesses in humans, possesses highly reduced and divergent mitochondrion-related organelles (MROs) called mitosomes. This organelle lacks many features associated with canonical aerobic mitochondria and even other MROs such as hydrogenosomes. The Entamoeba mitosome has been found to have a compartmentalized sulfate activation pathway, which was recently implicated to have a role in amebic stage conversion. It also features a unique shuttle system via Tom60, which delivers proteins from the cytosol to the mitosome. In addition, only Entamoeba mitosomes possess a novel subclass of β-barrel outer membrane protein called MBOMP30. With the discoveries of such unique features of mitosomes of Entamoeba, there still remain a number of significant unanswered issues pertaining to this organelle. Particularly, the present understanding of the inner mitosomal membrane of Entamoeba is extremely limited. So far, only a few homologs for transporters of various substrates have been confirmed, while the components of the protein translocation complexes appear to be absent or are yet to be discovered. Employing a similar strategy as in our previous work, we collaborated to screen and discover mitosomal membrane proteins. Using a specialized prediction pipeline, we searched for proteins possessing α-helical transmembrane domains, which are unique to E. histolytica mitosomes. From the prediction algorithm, 25 proteins emerged as candidates, two of which were initially observed to be localized to the mitosomes. Further screening and analysis of the predicted proteins may provide clues to answer key questions on mitosomal evolution, biogenesis, dynamics, and biochemical processes. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.

    Directory of Open Access Journals (Sweden)

    Laura M J Ylinen

    2010-08-01

    Full Text Available TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.

  8. Self-Evolvable Systems Machine Learning in Social Media

    CERN Document Server

    Iordache, Octavian

    2012-01-01

    This monograph presents key method to successfully manage the growing  complexity of systems  where conventional engineering and scientific methodologies and technologies based on learning and adaptability come to their limits and new ways are nowadays required. The transition from adaptable to evolvable and finally to self-evolvable systems is highlighted, self-properties such as self-organization, self-configuration, and self-repairing are introduced and challenges and limitations of the self-evolvable engineering systems are evaluated.

  9. Evolutionary and Topological Properties of Genes and Community Structures in Human Gene Regulatory Networks.

    Science.gov (United States)

    Szedlak, Anthony; Smith, Nicholas; Liu, Li; Paternostro, Giovanni; Piermarocchi, Carlo

    2016-06-01

    The diverse, specialized genes present in today's lifeforms evolved from a common core of ancient, elementary genes. However, these genes did not evolve individually: gene expression is controlled by a complex network of interactions, and alterations in one gene may drive reciprocal changes in its proteins' binding partners. Like many complex networks, these gene regulatory networks (GRNs) are composed of communities, or clusters of genes with relatively high connectivity. A deep understanding of the relationship between the evolutionary history of single genes and the topological properties of the underlying GRN is integral to evolutionary genetics. Here, we show that the topological properties of an acute myeloid leukemia GRN and a general human GRN are strongly coupled with its genes' evolutionary properties. Slowly evolving ("cold"), old genes tend to interact with each other, as do rapidly evolving ("hot"), young genes. This naturally causes genes to segregate into community structures with relatively homogeneous evolutionary histories. We argue that gene duplication placed old, cold genes and communities at the center of the networks, and young, hot genes and communities at the periphery. We demonstrate this with single-node centrality measures and two new measures of efficiency, the set efficiency and the interset efficiency. We conclude that these methods for studying the relationships between a GRN's community structures and its genes' evolutionary properties provide new perspectives for understanding evolutionary genetics.

  10. Adapting Morphology to Multiple Tasks in Evolved Virtual Creatures

    DEFF Research Database (Denmark)

    Lessin, Dan; Fussell, Don; Miikkulainen, Risto

    2014-01-01

    The ESP method for evolving virtual creatures (Lessin et al., 2013) consisted of an encapsulation mechanism to preserve learned skills, a human-designed syllabus to build higherlevel skills by combining lower-level skills systematically, and a pandemonium mechanism to resolve conflicts between...... encapsulated skills in a single creature’s brain. Previous work with ESP showed that it is possible to evolve much more complex behavior than before, even when fundamental morphology (i.e., skeletal segments and joints) was evolved only for the first skill. This paper introduces a more general form of ESP...... in which full morphological development can continue beyond the first skill, allowing creatures to adapt their morphology to multiple tasks. This extension increases the variety and quality of evolved creature results significantly, while maintaining the original ESP system’s ability to incrementally...

  11. Orthogonally Evolved AI to Improve Difficulty Adjustment in Video Games

    DEFF Research Database (Denmark)

    Hintze, Arend; Olson, Randal; Lehman, Joel Anthony

    2016-01-01

    (i.e. agents subject to fewer generations of evolution) make for easier opponents, while highly-evolved agents are more challenging to overcome. In this publication we test a new approach for difficulty adjustment in games: orthogonally evolved AI, where the player receives support from collaborating...... agents that are co-evolved with opponent agents (where collaborators and opponents have orthogonal incentives). The advantage is that game difficulty can be adjusted more granularly by manipulating two independent axes: by having more or less adept collaborators, and by having more or less adept...... opponents. Furthermore, human interaction can modulate (and be informed by) the performance and behavior of collaborating agents. In this way, orthogonally evolved AI both facilitates smoother difficulty adjustment and enables new game experiences....

  12. Evolving the Evolving: Territory, Place and Rewilding in the California Delta

    Directory of Open Access Journals (Sweden)

    Brett Milligan

    2017-10-01

    Full Text Available Current planning and legislation in California’s Sacramento-San Joaquin Delta call for the large-scale ecological restoration of aquatic and terrestrial habitats. These ecological mandates have emerged in response to the region’s infrastructural transformation and the Delta’s predominant use as the central logistical hub in the state’s vast water conveyance network. Restoration is an attempt to recover what was externalized by the logic and abstractions of this logistical infrastructure. However, based on findings from our research, which examined how people are using restored and naturalized landscapes in the Delta and how these landscapes are currently planned for, we argue that as mitigatory response, restoration planning continues some of the same spatial abstractions and inequities by failing to account for the Delta as an urbanized, cultural and unique place. In interpreting how these conditions have come to be, we give attention to a pluralistic landscape approach and a coevolutionary reading of planning, policy, science and landscapes to discuss the conservation challenges presented by “Delta as an Evolving Place”. We suggest that for rewilding efforts to be successful in the Delta, a range of proactive, opportunistic, grounded and participatory tactics will be required to shift towards a more socio-ecological approach.

  13. (N+1)-dimensional Lorentzian evolving wormholes supported by polytropic matter

    Energy Technology Data Exchange (ETDEWEB)

    Cataldo, Mauricio [Universidad del Bio-Bio, Departamento de Fisica, Facultad de Ciencias, Concepcion (Chile); Arostica, Fernanda; Bahamonde, Sebastian [Universidad de Concepcion, Departamento de Fisica, Concepcion (Chile)

    2013-08-15

    In this paper we study (N+1)-dimensional evolving wormholes supported by energy satisfying a polytropic equation of state. The considered evolving wormhole models are described by a constant redshift function and generalizes the standard flat Friedmann-Robertson-Walker spacetime. The polytropic equation of state allows us to consider in (3+1)-dimensions generalizations of the phantom energy and the generalized Chaplygin gas sources. (orig.)

  14. Identification and Gene Expression Analysis of a Taxonomically Restricted Cysteine-Rich Protein Family in Reef-Building Corals

    Science.gov (United States)

    Sunagawa, Shinichi; DeSalvo, Michael K.; Voolstra, Christian R.; Reyes-Bermudez, Alejandro; Medina, Mónica

    2009-01-01

    The amount of genomic sequence information continues to grow at an exponential rate, while the identification and characterization of genes without known homologs remains a major challenge. For non-model organisms with limited resources for manipulative studies, high-throughput transcriptomic data combined with bioinformatics methods provide a powerful approach to obtain initial insights into the function of unknown genes. In this study, we report the identification and characterization of a novel family of putatively secreted, small, cysteine-rich proteins herein named Small Cysteine-Rich Proteins (SCRiPs). Their discovery in expressed sequence tag (EST) libraries from the coral Montastraea faveolata required the performance of an iterative search strategy based on BLAST and Hidden-Markov-Model algorithms. While a discernible homolog could neither be identified in the genome of the sea anemone Nematostella vectensis, nor in a large EST dataset from the symbiotic sea anemone Aiptasia pallida, we identified SCRiP sequences in multiple scleractinian coral species. Therefore, we postulate that this gene family is an example of lineage-specific gene expansion in reef-building corals. Previously published gene expression microarray data suggest that a sub-group of SCRiPs is highly responsive to thermal stress. Furthermore, data from microarray experiments investigating developmental gene expression in the coral Acropora millepora suggest that different SCRiPs may play distinct roles in the development of corals. The function of these proteins remains to be elucidated, but our results from in silico, transcriptomic, and phylogenetic analyses provide initial insights into the evolution of SCRiPs, a novel, taxonomically restricted gene family that may be responsible for a lineage-specific trait in scleractinian corals. PMID:19283069

  15. Identification and gene expression analysis of a taxonomically restricted cysteine-rich protein family in reef-building corals.

    Directory of Open Access Journals (Sweden)

    Shinichi Sunagawa

    Full Text Available The amount of genomic sequence information continues to grow at an exponential rate, while the identification and characterization of genes without known homologs remains a major challenge. For non-model organisms with limited resources for manipulative studies, high-throughput transcriptomic data combined with bioinformatics methods provide a powerful approach to obtain initial insights into the function of unknown genes. In this study, we report the identification and characterization of a novel family of putatively secreted, small, cysteine-rich proteins herein named Small Cysteine-Rich Proteins (SCRiPs. Their discovery in expressed sequence tag (EST libraries from the coral Montastraea faveolata required the performance of an iterative search strategy based on BLAST and Hidden-Markov-Model algorithms. While a discernible homolog could neither be identified in the genome of the sea anemone Nematostella vectensis, nor in a large EST dataset from the symbiotic sea anemone Aiptasia pallida, we identified SCRiP sequences in multiple scleractinian coral species. Therefore, we postulate that this gene family is an example of lineage-specific gene expansion in reef-building corals. Previously published gene expression microarray data suggest that a sub-group of SCRiPs is highly responsive to thermal stress. Furthermore, data from microarray experiments investigating developmental gene expression in the coral Acropora millepora suggest that different SCRiPs may play distinct roles in the development of corals. The function of these proteins remains to be elucidated, but our results from in silico, transcriptomic, and phylogenetic analyses provide initial insights into the evolution of SCRiPs, a novel, taxonomically restricted gene family that may be responsible for a lineage-specific trait in scleractinian corals.

  16. Gene duplication as a major force in evolution

    Indian Academy of Sciences (India)

    Gene duplication is an important mechanism for acquiring new genes and creating genetic novelty in organisms. Many new gene functions have evolved through gene duplication and it has contributed tremendously to the evolution of developmental programmes in various organisms. Gene duplication can result from ...

  17. The aldehyde dehydrogenase, AldA, is essential for L-1,2-propanediol utilization in laboratory-evolved Escherichia coli

    DEFF Research Database (Denmark)

    Aziz, Ramy K.; Monk, Jonathan M.; Andrews, Kathleen A.

    2017-01-01

    Most Escherichia coli strains are naturally unable to grow on 1,2-propanediol (PDO) as a sole carbon source. Recently, however, a K-12 descendent E. coli strain was evolved to grow on 1,2-PDO, and it was hypothesized that this evolved ability was dependent on the aldehyde dehydrogenase, AldA, which...... is highly conserved among members of the family Enterobacteriacea. To test this hypothesis, we first performed computational model simulation, which confirmed the essentiality of the aldA gene for 1,2-PDO utilization by the evolved PDO-degrading E. coli. Next, we deleted the aldA gene from the evolved....... coli robustness, demonstrated by the bacterial deployment of a generalist enzyme (here AldA) in multiple pathways to survive carbon starvation and to grow on a non-native substrate when no native carbon source is available....

  18. Dynamic evolution of bitter taste receptor genes in vertebrates

    Directory of Open Access Journals (Sweden)

    Jones Gareth

    2009-01-01

    Full Text Available Abstract Background Sensing bitter tastes is crucial for many animals because it can prevent them from ingesting harmful foods. This process is mainly mediated by the bitter taste receptors (T2R, which are largely expressed in the taste buds. Previous studies have identified some T2R gene repertoires, and marked variation in repertoire size has been noted among species. However, the mechanisms underlying the evolution of vertebrate T2R genes remain poorly understood. Results To better understand the evolutionary pattern of these genes, we identified 16 T2R gene repertoires based on the high coverage genome sequences of vertebrates and studied the evolutionary changes in the number of T2R genes during birth-and-death evolution using the reconciled-tree method. We found that the number of T2R genes and the fraction of pseudogenes vary extensively among species. Based on the results of phylogenetic analysis, we showed that T2R gene families in teleost fishes are more diverse than those in tetrapods. In addition to the independent gene expansions in teleost fishes, frogs and mammals, lineage-specific gene duplications were also detected in lizards. Furthermore, extensive gains and losses of T2R genes were detected in each lineage during their evolution, resulting in widely differing T2R gene repertoires. Conclusion These results further support the hypotheses that T2R gene repertoires are closely related to the dietary habits of different species and that birth-and-death evolution is associated with adaptations to dietary changes.

  19. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  20. Comparative genomic analysis of Drosophila melanogaster and vector mosquito developmental genes.

    Directory of Open Access Journals (Sweden)

    Susanta K Behura

    Full Text Available Genome sequencing projects have presented the opportunity for analysis of developmental genes in three vector mosquito species: Aedes aegypti, Culex quinquefasciatus, and Anopheles gambiae. A comparative genomic analysis of developmental genes in Drosophila melanogaster and these three important vectors of human disease was performed in this investigation. While the study was comprehensive, special emphasis centered on genes that 1 are components of developmental signaling pathways, 2 regulate fundamental developmental processes, 3 are critical for the development of tissues of vector importance, 4 function in developmental processes known to have diverged within insects, and 5 encode microRNAs (miRNAs that regulate developmental transcripts in Drosophila. While most fruit fly developmental genes are conserved in the three vector mosquito species, several genes known to be critical for Drosophila development were not identified in one or more mosquito genomes. In other cases, mosquito lineage-specific gene gains with respect to D. melanogaster were noted. Sequence analyses also revealed that numerous repetitive sequences are a common structural feature of Drosophila and mosquito developmental genes. Finally, analysis of predicted miRNA binding sites in fruit fly and mosquito developmental genes suggests that the repertoire of developmental genes targeted by miRNAs is species-specific. The results of this study provide insight into the evolution of developmental genes and processes in dipterans and other arthropods, serve as a resource for those pursuing analysis of mosquito development, and will promote the design and refinement of functional analysis experiments.

  1. Primary Progressive Multiple Sclerosis Evolving From Radiologically Isolated Syndrome.

    Science.gov (United States)

    Kantarci, Orhun H; Lebrun, Christine; Siva, Aksel; Keegan, Mark B; Azevedo, Christina J; Inglese, Matilde; Tintoré, Mar; Newton, Braeden D; Durand-Dubief, Francoise; Amato, Maria Pia; De Stefano, Nicola; Sormani, Maria Pia; Pelletier, Daniel; Okuda, Darin T

    2016-02-01

    The aim of this work was to evaluate the preprogressive phase in subjects with radiologically isolated syndrome (RIS) who evolve to primary progressive multiple sclerosis (PPMS). A multicenter RIS cohort was previously established. Demographic, clinical, and radiological characteristics of subjects with RIS that evolved directly to PPMS were compared to those that developed a relapsing disease course from onset (clinically isolated syndrome [CIS] or relapsing-remitting MS) and were also compared to two other population- and clinic-based PPMS cohorts. Of the 453 subjects with RIS, 128 evolved to symptomatic MS during the follow-up (113 developed a first acute clinical event consistent with CIS/MS, 15 evolved to PPMS). PPMS prevalence (11.7%) and onset age (mean ± standard deviation; 49.1 ± 12.1) in the RIS group were comparable to other PPMS populations (p > 0.05). Median time to PPMS was 3.5 years (range, 1.6-5.4). RIS evolved to PPMS more commonly in men (p = 0.005) and at an older age (p < 0.001) when compared to CIS/MS, independent of follow-up duration. Subjects who evolved to PPMS had more spinal cord lesions (100%) before symptomatic evolution than those that developed CIS/MS (64%) and those that remained asymptomatic (23%) within the follow-up period (P = 0.005). Other MRI characteristics in the preprogressive phase of PPMS were indistinguishable from CIS/MS. Subjects with RIS evolve to PPMS at the same frequency as expected from general MS populations in an age-dependent manner. Besides age, unequivocal presence of spinal cord lesions and being male predicted evolution to PPMS. Our findings further suggest that RIS is biologically part of the MS spectrum. © 2015 American Neurological Association.

  2. Evolvability of feed-forward loop architecture biases its abundance in transcription networks

    Directory of Open Access Journals (Sweden)

    Widder Stefanie

    2012-01-01

    Full Text Available Abstract Background Transcription networks define the core of the regulatory machinery of cellular life and are largely responsible for information processing and decision making. At the small scale, interaction motifs have been characterized based on their abundance and some seemingly general patterns have been described. In particular, the abundance of different feed-forward loop motifs in gene regulatory networks displays systematic biases towards some particular topologies, which are much more common than others. The causative process of this pattern is still matter of debate. Results We analyzed the entire motif-function landscape of the feed-forward loop using the formalism developed in a previous work. We evaluated the probabilities to implement possible functions for each motif and found that the kurtosis of these distributions correlate well with the natural abundance pattern. Kurtosis is a standard measure for the peakedness of probability distributions. Furthermore, we examined the functional robustness of the motifs facing mutational pressure in silico and observed that the abundance pattern is biased by the degree of their evolvability. Conclusions The natural abundance pattern of the feed-forward loop can be reconstructed concerning its intrinsic plasticity. Intrinsic plasticity is associated to each motif in terms of its capacity of implementing a repertoire of possible functions and it is directly linked to the motif's evolvability. Since evolvability is defined as the potential phenotypic variation of the motif upon mutation, the link plausibly explains the abundance pattern.

  3. Evolvability of feed-forward loop architecture biases its abundance in transcription networks.

    Science.gov (United States)

    Widder, Stefanie; Solé, Ricard; Macía, Javier

    2012-01-19

    Transcription networks define the core of the regulatory machinery of cellular life and are largely responsible for information processing and decision making. At the small scale, interaction motifs have been characterized based on their abundance and some seemingly general patterns have been described. In particular, the abundance of different feed-forward loop motifs in gene regulatory networks displays systematic biases towards some particular topologies, which are much more common than others. The causative process of this pattern is still matter of debate. We analyzed the entire motif-function landscape of the feed-forward loop using the formalism developed in a previous work. We evaluated the probabilities to implement possible functions for each motif and found that the kurtosis of these distributions correlate well with the natural abundance pattern. Kurtosis is a standard measure for the peakedness of probability distributions. Furthermore, we examined the functional robustness of the motifs facing mutational pressure in silico and observed that the abundance pattern is biased by the degree of their evolvability. The natural abundance pattern of the feed-forward loop can be reconstructed concerning its intrinsic plasticity. Intrinsic plasticity is associated to each motif in terms of its capacity of implementing a repertoire of possible functions and it is directly linked to the motif's evolvability. Since evolvability is defined as the potential phenotypic variation of the motif upon mutation, the link plausibly explains the abundance pattern.

  4. The aldehyde dehydrogenase, AldA, is essential for L-1,2-propanediol utilization in laboratory-evolved Escherichia coli.

    Science.gov (United States)

    Aziz, Ramy K; Monk, Jonathan M; Andrews, Kathleen A; Nhan, Jenny; Khaw, Valerie L; Wong, Hesper; Palsson, Bernhard O; Charusanti, Pep

    2017-01-01

    Most Escherichia coli strains are naturally unable to grow on 1,2-propanediol (PDO) as a sole carbon source. Recently, however, a K-12 descendent E. coli strain was evolved to grow on 1,2-PDO, and it was hypothesized that this evolved ability was dependent on the aldehyde dehydrogenase, AldA, which is highly conserved among members of the family Enterobacteriacea. To test this hypothesis, we first performed computational model simulation, which confirmed the essentiality of the aldA gene for 1,2-PDO utilization by the evolved PDO-degrading E. coli. Next, we deleted the aldA gene from the evolved strain, and this deletion was sufficient to abolish the evolved phenotype. On re-introducing the gene on a plasmid, the evolved phenotype was restored. These findings provide experimental evidence for the computationally predicted role of AldA in 1,2-PDO utilization, and represent a good example of E. coli robustness, demonstrated by the bacterial deployment of a generalist enzyme (here AldA) in multiple pathways to survive carbon starvation and to grow on a non-native substrate when no native carbon source is available. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Modeling and clustering users with evolving profiles in usage streams

    KAUST Repository

    Zhang, Chongsheng

    2012-09-01

    Today, there is an increasing need of data stream mining technology to discover important patterns on the fly. Existing data stream models and algorithms commonly assume that users\\' records or profiles in data streams will not be updated or revised once they arrive. Nevertheless, in various applications such asWeb usage, the records/profiles of the users can evolve along time. This kind of streaming data evolves in two forms, the streaming of tuples or transactions as in the case of traditional data streams, and more importantly, the evolving of user records/profiles inside the streams. Such data streams bring difficulties on modeling and clustering for exploring users\\' behaviors. In this paper, we propose three models to summarize this kind of data streams, which are the batch model, the Evolving Objects (EO) model and the Dynamic Data Stream (DDS) model. Through creating, updating and deleting user profiles, these models summarize the behaviors of each user as a profile object. Based upon these models, clustering algorithms are employed to discover interesting user groups from the profile objects. We have evaluated all the proposed models on a large real-world data set, showing that the DDS model summarizes the data streams with evolving tuples more efficiently and effectively, and provides better basis for clustering users than the other two models. © 2012 IEEE.

  6. Effects of Gene Duplication, Positive Selection, and Shifts in Gene Expression on the Evolution of the Venom Gland Transcriptome in Widow Spiders

    Science.gov (United States)

    Haney, Robert A.; Clarke, Thomas H.; Gadgil, Rujuta; Fitzpatrick, Ryan; Hayashi, Cheryl Y.; Ayoub, Nadia A.; Garb, Jessica E.

    2016-01-01

    Gene duplication and positive selection can be important determinants of the evolution of venom, a protein-rich secretion used in prey capture and defense. In a typical model of venom evolution, gene duplicates switch to venom gland expression and change function under the action of positive selection, which together with further duplication produces large gene families encoding diverse toxins. Although these processes have been demonstrated for individual toxin families, high-throughput multitissue sequencing of closely related venomous species can provide insights into evolutionary dynamics at the scale of the entire venom gland transcriptome. By assembling and analyzing multitissue transcriptomes from the Western black widow spider and two closely related species with distinct venom toxicity phenotypes, we do not find that gene duplication and duplicate retention is greater in gene families with venom gland biased expression in comparison with broadly expressed families. Positive selection has acted on some venom toxin families, but does not appear to be in excess for families with venom gland biased expression. Moreover, we find 309 distinct gene families that have single transcripts with venom gland biased expression, suggesting that the switching of genes to venom gland expression in numerous unrelated gene families has been a dominant mode of evolution. We also find ample variation in protein sequences of venom gland–specific transcripts, lineage-specific family sizes, and ortholog expression among species. This variation might contribute to the variable venom toxicity of these species. PMID:26733576

  7. History of a prolific family: the Hes/Hey-related genes of the annelid Platynereis.

    Science.gov (United States)

    Gazave, Eve; Guillou, Aurélien; Balavoine, Guillaume

    2014-01-01

    The Hes superfamily or Hes/Hey-related genes encompass a variety of metazoan-specific bHLH genes, with somewhat fuzzy phylogenetic relationships. Hes superfamily members are involved in a variety of major developmental mechanisms in metazoans, notably in neurogenesis and segmentation processes, in which they often act as direct effector genes of the Notch signaling pathway. We have investigated the molecular and functional evolution of the Hes superfamily in metazoans using the lophotrochozoan Platynereis dumerilii as model. Our phylogenetic analyses of more than 200 Metazoan Hes/Hey-related genes revealed the presence of five families, three of them (Hes, Hey and Helt) being pan-metazoan. Those families were likely composed of a unique representative in the last common metazoan ancestor. The evolution of the Hes family was shaped by many independent lineage specific tandem duplication events. The expression patterns of 13 of the 15 Hes/Hey-related genes in Platynereis indicate a broad functional diversification. Nevertheless, a majority of these genes are involved in two crucial developmental processes in annelids: neurogenesis and segmentation, resembling functions highlighted in other animal models. Combining phylogenetic and expression data, our study suggests an unusual evolutionary history for the Hes superfamily. An ancestral multifunctional annelid Hes gene may have undergone multiples rounds of duplication-degeneration-complementation processes in the lineage leading to Platynereis, each gene copies ensuring their maintenance in the genome by subfunctionalisation. Similar but independent waves of duplications are at the origin of the multiplicity of Hes genes in other metazoan lineages.

  8. Evolving role of MeCP2 in Rett syndrome and autism

    Science.gov (United States)

    LaSalle, Janine M; Yasui, Dag H

    2010-01-01

    Rett syndrome is an X-linked autism-spectrum disorder caused by mutations in MECP2, encoding methyl CpG-binding protein 2. Since the discovery of MECP2 mutations as the genetic cause of Rett syndrome, the understanding of MeCP2 function has evolved. Although MeCP2 was predicted to be a global transcriptional repressor of methylated promoters, large-scale combined epigenomic approaches of MeCP2 binding, methylation and gene expression have demonstrated that MeCP2 binds preferentially to intergenic and intronic regions, and sparsely methylated promoters of active genes. This review compares the evolution of thought within two ‘classic’ epigenetic mechanisms of parental imprinting and X chromosome inactivation to that of the MeCP2 field, and considers the future relevance of integrated epigenomic databases to understanding autism and Rett syndrome. PMID:20473347

  9. Synthesis of Evolving Cells for Reconfigurable Manufacturing Systems

    Science.gov (United States)

    Padayachee, J.; Bright, G.

    2014-07-01

    The concept of Reconfigurable Manufacturing Systems (RMSs) was formulated due to the global necessity for production systems that are able to economically evolve according to changes in markets and products. Technologies and design methods are under development to enable RMSs to exhibit transformable system layouts, reconfigurable processes, cells and machines. Existing factory design methods and software have not yet advanced to include reconfigurable manufacturing concepts. This paper presents the underlying group technology framework for the design of manufacturing cells that are able to evolve according to a changing product mix by mechanisms of reconfiguration. The framework is based on a Norton- Bass forecast and time variant BOM models. An adaptation of legacy group technology methods is presented for the synthesis of evolving cells and two optimization problems are presented within this context.

  10. Evolving Systems: An Outcome of Fondest Hopes and Wildest Dreams

    Science.gov (United States)

    Frost, Susan A.; Balas, Mark J.

    2012-01-01

    New theory is presented for evolving systems, which are autonomously controlled subsystems that self-assemble into a new evolved system with a higher purpose. Evolving systems of aerospace structures often require additional control when assembling to maintain stability during the entire evolution process. This is the concept of Adaptive Key Component Control that operates through one specific component to maintain stability during the evolution. In addition, this control must often overcome persistent disturbances that occur while the evolution is in progress. Theoretical results will be presented for Adaptive Key Component control for persistent disturbance rejection. An illustrative example will demonstrate the Adaptive Key Component controller on a system composed of rigid body and flexible body modes.

  11. Computational Genetic Regulatory Networks Evolvable, Self-organizing Systems

    CERN Document Server

    Knabe, Johannes F

    2013-01-01

    Genetic Regulatory Networks (GRNs) in biological organisms are primary engines for cells to enact their engagements with environments, via incessant, continually active coupling. In differentiated multicellular organisms, tremendous complexity has arisen in the course of evolution of life on earth. Engineering and science have so far achieved no working system that can compare with this complexity, depth and scope of organization. Abstracting the dynamics of genetic regulatory control to a computational framework in which artificial GRNs in artificial simulated cells differentiate while connected in a changing topology, it is possible to apply Darwinian evolution in silico to study the capacity of such developmental/differentiated GRNs to evolve. In this volume an evolutionary GRN paradigm is investigated for its evolvability and robustness in models of biological clocks, in simple differentiated multicellularity, and in evolving artificial developing 'organisms' which grow and express an ontogeny starting fr...

  12. Study on evolving phases of accelerating generalized polygon beams.

    Science.gov (United States)

    Zhang, Yuntian; Dong, Fengliang; Qian, Kemao; Zhang, Qingchuan; Chu, Weiguo; Ma, Xuan; Wu, Xiaoping

    2016-03-07

    Recently, accelerating beam is becoming a hotspot in optics research. In this paper, we studied the evolving phases of accelerating generalized polygon beams (AGPBs) and proposed a novel method to generate this beam family. An important discovery has been made about reconstructing AGPBs only by evolving low-frequency phases in high power region, which confirms the dominant role of phase terms in the AGPBs' evolution. We also succeeded controlling the size and quantity of AGPB's intensity peaks in an easy and direct manner by manipulating the evolving phases in low frequency. This result not only explains the self-healing property of AGPBs but also confirms that AGPBs can be a great candidate to function as an optical tweezer to trap and free microparticles and microcreatures for certain purpose.

  13. Cosmic Biology How Life Could Evolve on Other Worlds

    CERN Document Server

    Irwin, Louis Neil

    2011-01-01

    It is very unlikely that little green humanoids are living on Mars. But what are the possible life forms that might exist in our Solar System and how might they have evolved? This uniquely authoritative and imaginative book on the possibilties for alien life addresses the intrinsic interest that we have about life on other worlds - reinforcing some of our assumptions and reshaping others. It introduces new possibilties that will enlarge our understanding of the issue overall, in particular the enormous range of environments and planetary conditions within which life might evolve. Cosmic Biology -discusses a broad range of possible environments where alien life might have evolved; -explains why carbon-based, water-borne life is more likely that its alternatives, but is not the only possiblity; -applies the principles of planetary science and modern biology to evolutionary scenarios on other worlds; -looks at the future fates of living systems, including those on Earth.

  14. Qualitative Functional Decomposition Analysis of Evolved Neuromorphic Flight Controllers

    Directory of Open Access Journals (Sweden)

    Sanjay K. Boddhu

    2012-01-01

    Full Text Available In the previous work, it was demonstrated that one can effectively employ CTRNN-EH (a neuromorphic variant of EH method methodology to evolve neuromorphic flight controllers for a flapping wing robot. This paper describes a novel frequency grouping-based analysis technique, developed to qualitatively decompose the evolved controllers into explainable functional control blocks. A summary of the previous work related to evolving flight controllers for two categories of the controller types, called autonomous and nonautonomous controllers, is provided, and the applicability of the newly developed decomposition analysis for both controller categories is demonstrated. Further, the paper concludes with appropriate discussion of ongoing work and implications for possible future work related to employing the CTRNN-EH methodology and the decomposition analysis techniques presented in this paper.

  15. A burst of ABC genes in the genome of the polyphagous spider mite Tetranychus urticae.

    Science.gov (United States)

    Dermauw, Wannes; Osborne, Edward John; Clark, Richard M; Grbić, Miodrag; Tirry, Luc; Van Leeuwen, Thomas

    2013-05-10

    The ABC (ATP-binding cassette) gene superfamily is widespread across all living species. The majority of ABC genes encode ABC transporters, which are membrane-spanning proteins capable of transferring substrates across biological membranes by hydrolyzing ATP. Although ABC transporters have often been associated with resistance to drugs and toxic compounds, within the Arthropoda ABC gene families have only been characterized in detail in several insects and a crustacean. In this study, we report a genome-wide survey and expression analysis of the ABC gene superfamily in the spider mite, Tetranychus urticae, a chelicerate ~ 450 million years diverged from other Arthropod lineages. T. urticae is a major agricultural pest, and is among of the most polyphagous arthropod herbivores known. The species resists a staggering array of toxic plant secondary metabolites, and has developed resistance to all major classes of pesticides in use for its control. We identified 103 ABC genes in the T. urticae genome, the highest number discovered in a metazoan species to date. Within the T. urticae ABC gene set, all members of the eight currently described subfamilies (A to H) were detected. A phylogenetic analysis revealed that the high number of ABC genes in T. urticae is due primarily to lineage-specific expansions of ABC genes within the ABCC, ABCG and ABCH subfamilies. In particular, the ABCC subfamily harbors the highest number of T. urticae ABC genes (39). In a comparative genomic analysis, we found clear orthologous relationships between a subset of T. urticae ABC proteins and ABC proteins in both vertebrates and invertebrates known to be involved in fundamental cellular processes. These included members of the ABCB-half transporters, and the ABCD, ABCE and ABCF families. Furthermore, one-to-one orthologues could be distinguished between T. urticae proteins and human ABCC10, ABCG5 and ABCG8, the Drosophila melanogaster sulfonylurea receptor and ecdysone-regulated transporter E

  16. The cartography of pain: the evolving contribution of pain maps.

    Science.gov (United States)

    Schott, Geoffrey D

    2010-09-01

    Pain maps are nowadays widely used in clinical practice. This article aims to critically review the fundamental principles that underlie the mapping of pain, to analyse the evolving iconography of pain maps and their sometimes straightforward and sometimes contentious nature when used in the clinic, and to draw attention to some more recent developments in mapping pain. It is concluded that these maps are intriguing and evolving cartographic tools which can be used for depicting not only the spatial features but also the interpretative or perceptual components and accompaniments of pain. Copyright 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.

  17. 1. History, evolution, and evolving standards of contact lens care.

    Science.gov (United States)

    Szczotka-Flynn, Loretta; Ahearn, Donald G; Barr, Joseph; Benjamin, William Joe; Kiang, Tina; Nichols, Jason J; Schein, Oliver D; Stone, Ralph P; Winterton, Lynn

    2013-01-15

    Contact lenses and lens care regimens are an important part of eyecare practices and vital to lens-wearing patients. New contact lens materials and cleaning options continue to come to market and affect how patients wear and care for their lenses. In this section we look at how the contact lens and lens solution revolution started, how it has evolved over the last 40 years, and how standards have evolved and impacted these new offerings. Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  18. Active Printed Materials for Complex Self-Evolving Deformations

    Science.gov (United States)

    Raviv, Dan; Zhao, Wei; McKnelly, Carrie; Papadopoulou, Athina; Kadambi, Achuta; Shi, Boxin; Hirsch, Shai; Dikovsky, Daniel; Zyracki, Michael; Olguin, Carlos; Raskar, Ramesh; Tibbits, Skylar

    2014-12-01

    We propose a new design of complex self-evolving structures that vary over time due to environmental interaction. In conventional 3D printing systems, materials are meant to be stable rather than active and fabricated models are designed and printed as static objects. Here, we introduce a novel approach for simulating and fabricating self-evolving structures that transform into a predetermined shape, changing property and function after fabrication. The new locally coordinated bending primitives combine into a single system, allowing for a global deformation which can stretch, fold and bend given environmental stimulus.

  19. Transcription factor Glis3, a novel critical player in the regulation of pancreatic beta-cell development and insulin gene expression.

    Science.gov (United States)

    Kang, Hong Soon; Kim, Yong-Sik; ZeRuth, Gary; Beak, Ju Youn; Gerrish, Kevin; Kilic, Gamze; Sosa-Pineda, Beatriz; Jensen, Jan; Pierreux, Christophe E; Lemaigre, Frederic P; Foley, Julie; Jetten, Anton M

    2009-12-01

    In this study, we report that the Krüppel-like zinc finger transcription factor Gli-similar 3 (Glis3) is induced during the secondary transition of pancreatic development, a stage of cell lineage specification and extensive patterning, and that Glis3(zf/zf) mutant mice develop neonatal diabetes, evidenced by hyperglycemia and hypoinsulinemia. The Glis3(zf/zf) mutant mouse pancreas shows a dramatic loss of beta and delta cells, contrasting a smaller relative loss of alpha, PP, and epsilon cells. In addition, Glis3(zf/zf) mutant mice develop ductal cysts, while no significant changes were observed in acini. Gene expression profiling and immunofluorescent staining demonstrated that the expression of pancreatic hormones and several transcription factors important in endocrine cell development, including Ngn3, MafA, and Pdx1, were significantly decreased in the developing pancreata of Glis3(zf/zf) mutant mice. The population of pancreatic progenitors appears not to be greatly affected in Glis3(zf/zf) mutant mice; however, the number of neurogenin 3 (Ngn3)-positive endocrine cell progenitors is significantly reduced. Our study indicates that Glis3 plays a key role in cell lineage specification, particularly in the development of mature pancreatic beta cells. In addition, we provide evidence that Glis3 regulates insulin gene expression through two Glis-binding sites in its proximal promoter, indicating that Glis3 also regulates beta-cell function.

  20. FOXN1: a master regulator gene of thymic epithelial development programme

    Directory of Open Access Journals (Sweden)

    Rosa eRomano

    2013-07-01

    Full Text Available T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs drive T cell differentiation, education and selection processes, while the thymocyte-dependent signals allow TECs to maturate and provide an appropriate thymic microenvironment. Alterations in genes implicated in thymus organogenesis, including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1 and Six1, affect this well-orchestrated process, leading to disruption of thymic architecture. Of note, in both human and mice, the primordial TECs are yet unable to fully support T cell development and only after the transcriptional activation of the Forkhead-box n1 (FOXN1 gene in the thymic epithelium this essential function is acquired. FOXN1 is a master regulator in the TEC lineage specification in that it down-stream promotes transcription of genes, which, in turn, regulate TECs differentiation. In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC homeostasis in the postnatal thymus. An inborn null mutation in FOXN1 leads to Nude/SCID phenotype in mouse, rat and humans. In Foxn1-/- nude animals, initial formation of the primordial organ is arrested and the primordium is not colonized by hematopoietic precursors, causing a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail dystrophy and a severe T cell immunodeficiency, inherited as an autosomal recessive disorder. Aim of this review is to summarize all the scientific information so far available to better characterize the pivotal role of the master regulator FOXN1 transcription factor in the TEC lineage specifications and functionality.

  1. A Nonsynonymous SNP Catalog of Mycobacterium tuberculosis Virulence Genes and Its Use for Detecting New Potentially Virulent Sublineages.

    Science.gov (United States)

    Mikheecheva, Natalya E; Zaychikova, Marina V; Melerzanov, Alexander V; Danilenko, Valery N

    2017-04-01

    Mycobacterium tuberculosis is divided into several distinct lineages, and various genetic markers such as IS-elements, VNTR, and SNPs are used for lineage identification. We propose an M. tuberculosis classification approach based on functional polymorphisms in virulence genes. An M. tuberculosis virulence genes catalog has been established, including 319 genes from various protein groups, such as proteases, cell wall proteins, fatty acid and lipid metabolism proteins, sigma factors, toxin-antitoxin systems. Another catalog of 1,573 M. tuberculosis isolates of different lineages has been developed. The developed SNP-calling program has identified 3,563 nonsynonymous SNPs. The constructed SNP-based phylogeny reflected the evolutionary relationship between lineages and detected new sublineages. SNP analysis of sublineage F15/LAM4/KZN revealed four lineage-specific mutations in cyp125, mce3B, vapC25, and vapB34. The Ural lineage has been divided into two geographical clusters based on different SNPs in virulence genes. A new sublineage, B0/N-90, was detected inside the Beijing-B0/W-148 by SNPs in irtB, mce3F and vapC46. We have found 27 members of B0/N-90 among the 227 available genomes of the Beijing-B0/W-148 sublineage. Whole-genome sequencing of strain B9741, isolated from an HIV-positive patient, was demonstrated to belong to the new B0/N-90 group. A primer set for PCR detection of B0/N-90 lineage-specific mutations has been developed. The prospective use of mce3 mutant genes as genetically engineered vaccine is discussed. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  2. Evolving matched filter transform pairs for satellite image processing

    Science.gov (United States)

    Peterson, Michael R.; Horner, Toby; Moore, Frank

    2011-06-01

    Wavelets provide an attractive method for efficient image compression. For transmission across noisy or bandwidth limited channels, a signal may be subjected to quantization in which the signal is transcribed onto a reduced alphabet in order to save bandwidth. Unfortunately, the performance of the discrete wavelet transform (DWT) degrades at increasing levels of quantization. In recent years, evolutionary algorithms (EAs) have been employed to optimize wavelet-inspired transform filters to improve compression performance in the presence of quantization. Wavelet filters consist of a pair of real-valued coefficient sets; one set represents the compression filter while the other set defines the image reconstruction filter. The reconstruction filter is defined as the biorthogonal inverse of the compression filter. Previous research focused upon two approaches to filter optimization. In one approach, the original wavelet filter is used for image compression while the reconstruction filter is evolved by an EA. In the second approach, both the compression and reconstruction filters are evolved. In both cases, the filters are not biorthogonally related to one another. We propose a novel approach to filter evolution. The EA optimizes a compression filter. Rather than using a wavelet filter or evolving a second filter for reconstruction, the reconstruction filter is computed as the biorthogonal inverse of the evolved compression filter. The resulting filter pair retains some of the mathematical properties of wavelets. This paper compares this new approach to existing filter optimization approaches to determine its suitability for the optimization of image filters appropriate for defense applications of image processing.

  3. Functional properties of the oxygen evolving complex of photosystem 2

    NARCIS (Netherlands)

    Vliet, van P.H.

    1996-01-01


    This Thesis presents the results of a study by electron paramagnetic resonance (EPR) and measurements of oxygen evolution of the Oxygen Evolving Complex of Photosystem 11 (PS-II) in PS-II enriched membranes from spinach.

    The experimental part of this Thesis is preceded by a

  4. Evolving fuzzy rules for relaxed-criteria negotiation.

    Science.gov (United States)

    Sim, Kwang Mong

    2008-12-01

    In the literature on automated negotiation, very few negotiation agents are designed with the flexibility to slightly relax their negotiation criteria to reach a consensus more rapidly and with more certainty. Furthermore, these relaxed-criteria negotiation agents were not equipped with the ability to enhance their performance by learning and evolving their relaxed-criteria negotiation rules. The impetus of this work is designing market-driven negotiation agents (MDAs) that not only have the flexibility of relaxing bargaining criteria using fuzzy rules, but can also evolve their structures by learning new relaxed-criteria fuzzy rules to improve their negotiation outcomes as they participate in negotiations in more e-markets. To this end, an evolutionary algorithm for adapting and evolving relaxed-criteria fuzzy rules was developed. Implementing the idea in a testbed, two kinds of experiments for evaluating and comparing EvEMDAs (MDAs with relaxed-criteria rules that are evolved using the evolutionary algorithm) and EMDAs (MDAs with relaxed-criteria rules that are manually constructed) were carried out through stochastic simulations. Empirical results show that: 1) EvEMDAs generally outperformed EMDAs in different types of e-markets and 2) the negotiation outcomes of EvEMDAs generally improved as they negotiated in more e-markets.

  5. On the Benefits of Divergent Search for Evolved Representations

    DEFF Research Database (Denmark)

    Lehman, Joel; Risi, Sebastian; Stanley, Kenneth O

    2012-01-01

    explicit objectives that are consequently divergent may implicitly reward lineages that continually diverge, thereby indirectly selecting for evolvable representations that are better able to diverge further. This paper reviews a range of past results that support such a hypothesis from a method called...

  6. Fast, comfortable or economical: Evolving platooning strategies with many objectives

    NARCIS (Netherlands)

    Willigen, W. van; Haasdijk, E.; Kester, L.J.H.M.

    2013-01-01

    The research in this paper is inspired by a vision of intelligent vehicles that autonomously move along motorways: they join and leave trains of vehicles (platoons), overtake other vehicles, etc. We propose a multi-objective evolutionary algorithm that evolves high-level controllers for such

  7. Evolving Robot Controllers for Structured Environments Through Environment Decomposition

    DEFF Research Database (Denmark)

    Moreno, Rodrigo; Faiña, Andres; Støy, Kasper

    2015-01-01

    into four different sub-environments and evolve controllers that generalize to traverse two larger environments composed of the sub-environments. We also study two strategies for presenting the sub-environments to the evolutionary algorithm: all sub-environments at the same time and in sequence. Results...

  8. The urban watershed continuum: evolving spatial and temporal dimensions

    Science.gov (United States)

    Sujay S. Kaushal; Kenneth T. Belt

    2012-01-01

    Urban ecosystems are constantly evolving, and they are expected to change in both space and time with active management or degradation. An urban watershed continuum framework recognizes a continuum of engineered and natural hydrologic flowpaths that expands hydrologic networks in ways that are seldom considered. It recognizes that the nature of hydrologic connectivity...

  9. Did language evolve like the vertebrate eye? | Botha | Stellenbosch ...

    African Journals Online (AJOL)

    Did language evolve like the vertebrate eye? R P Botha. Abstract. No abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.5774/34-0-33 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

  10. A Review of Microbiology: An Evolving Science, Second Edition

    Directory of Open Access Journals (Sweden)

    Barbara May

    2011-09-01

    Full Text Available Review of: Microbiology: An Evolving Science, 2nd ed.; Joan L Slonczweski and John W. Foster; (2011. W.W. Norton & Company, New York NY. 1096 pages. ISBN: 978-0-393-93447-2. Normal 0 false false false EN-US X-NONE X-NONE

  11. The Evolving Military Learner Population: A Review of the Literature

    Science.gov (United States)

    Ford, Kate; Vignare, Karen

    2015-01-01

    This literature review examines the evolving online military learner population with emphasis on current generation military learners, who are most frequently Post-9/11 veterans. The review synthesizes recent scholarly and grey literature on military learner demographics and attributes, college experiences, and academic outcomes against a backdrop…

  12. Developing Collective Learning Extension for Rapidly Evolving Information System Courses

    Science.gov (United States)

    Agarwal, Nitin; Ahmed, Faysal

    2017-01-01

    Due to rapidly evolving Information System (IS) technologies, instructors find themselves stuck in the constant game of catching up. On the same hand students find their skills obsolete almost as soon as they graduate. As part of IS curriculum and education, we need to emphasize more on teaching the students "how to learn" while keeping…

  13. Evolving Nature of Sexual Orientation and Gender Identity

    Science.gov (United States)

    Jourian, T. J.

    2015-01-01

    This chapter discusses the historical and evolving terminology, constructs, and ideologies that inform the language used by those who are lesbian, gay, bisexual, and same-gender loving, who may identify as queer, as well as those who are members of trans* communities from multiple and intersectional perspectives.

  14. Optimists' Creed: Brave New Cyberlearning, Evolving Utopias (Circa 2041)

    Science.gov (United States)

    Burleson, Winslow; Lewis, Armanda

    2016-01-01

    This essay imagines the role that artificial intelligence innovations play in the integrated living, learning and research environments of 2041. Here, in 2041, in the context of increasingly complex wicked challenges, whose solutions by their very nature continue to evade even the most capable experts, society and technology have co-evolved to…

  15. A Conceptual Framework for Evolving, Recommender Online Learning Systems

    Science.gov (United States)

    Peiris, K. Dharini Amitha; Gallupe, R. Brent

    2012-01-01

    A comprehensive conceptual framework is developed and described for evolving recommender-driven online learning systems (ROLS). This framework describes how such systems can support students, course authors, course instructors, systems administrators, and policy makers in developing and using these ROLS. The design science information systems…

  16. Disaggregating soil erosion processes within an evolving experimental landscape

    Science.gov (United States)

    Soil-mantled landscapes subjected to rainfall, runoff events, and downstream base level adjustments will erode and evolve in time and space. Yet the precise mechanisms for soil erosion also will vary, and such variations may not be adequately captured by soil erosion prediction technology. This st...

  17. Thermogravimetry-evolved gas analysis–mass spectrometry system ...

    Indian Academy of Sciences (India)

    This system which gives complete information on weight change, heat change, nature and content of evolved gases is being used for. temperature programmed decomposition (TPD),; synthesis of nanocrystalline materials,; gas–solid interactions and; analysis of gas mixtures. The TPD of various inorganic oxyanion solids ...

  18. Generic, Property Based Queries for Evolvable Weaving Specifications

    NARCIS (Netherlands)

    Nagy, I.; Bergmans, Lodewijk; Gülesir, G.; Durr, P.E.A.; Aksit, Mehmet

    2005-01-01

    In the current aspect-oriented languages, advices and pointcuts are explicitly associated in general. This results in weaving specifications that are less evolvable and need more maintenance during the development of a system. To address this issue, we propose associative access to advices and

  19. Exploring, exploiting and evolving diversity of aquatic ecosystem models

    NARCIS (Netherlands)

    Janssen, A.B.G.; Arhonditsis, G.B.; Beusen, Arthur; Bolding, Karsten; Bruce, Louise; Bruggeman, Jorn; Couture, Raoul Marie; Downing, Andrea S.; Alex Elliott, J.; Frassl, M.A.; Gal, Gideon; Gerla, Daan J.; Hipsey, M.R.; Hu, Fenjuan; Ives, S.C.; Janse, J.H.; Jeppesen, Erik; Jöhnk, K.D.; Kneis, David; Kong, Xiangzhen; Kuiper, J.J.; Lehmann, M.K.; Lemmen, Carsten; Özkundakci, Deniz; Petzoldt, Thomas; Rinke, Karsten; Robson, B.J.; Sachse, René; Schep, S.A.; Schmid, Martin; Scholten, Huub; Teurlincx, Sven; Trolle, Dennis; Troost, T.A.; Dam, Van A.A.; Gerven, Van L.P.A.; Weijerman, Mariska; Wells, S.A.; Mooij, W.M.

    2015-01-01

    Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality

  20. Intelligent reservoir operation system based on evolving artificial neural networks

    Science.gov (United States)

    Chaves, Paulo; Chang, Fi-John

    2008-06-01

    We propose a novel intelligent reservoir operation system based on an evolving artificial neural network (ANN). Evolving means the parameters of the ANN model are identified by the GA evolutionary optimization technique. Accordingly, the ANN model should represent the operational strategies of reservoir operation. The main advantages of the Evolving ANN Intelligent System (ENNIS) are as follows: (i) only a small number of parameters to be optimized even for long optimization horizons, (ii) easy to handle multiple decision variables, and (iii) the straightforward combination of the operation model with other prediction models. The developed intelligent system was applied to the operation of the Shihmen Reservoir in North Taiwan, to investigate its applicability and practicability. The proposed method is first built to a simple formulation for the operation of the Shihmen Reservoir, with single objective and single decision. Its results were compared to those obtained by dynamic programming. The constructed network proved to be a good operational strategy. The method was then built and applied to the reservoir with multiple (five) decision variables. The results demonstrated that the developed evolving neural networks improved the operation performance of the reservoir when compared to its current operational strategy. The system was capable of successfully simultaneously handling various decision variables and provided reasonable and suitable decisions.

  1. The Evolving Status of Photojournalism Education. ERIC Digest.

    Science.gov (United States)

    Cookman, Claude

    Noting that new technologies are resulting in extensive changes in the field of photojournalism, both as it is practiced and taught, this Digest reviews this rapidly evolving field of education and professional practice. It discusses what digital photography is; the history of digital photography; how digital photography has changed…

  2. Sextant: Visualizing time-evolving linked geospatial data

    NARCIS (Netherlands)

    C. Nikolaou (Charalampos); K. Dogani (Kallirroi); K. Bereta (Konstantina); G. Garbis (George); M. Karpathiotakis (Manos); K. Kyzirakos (Konstantinos); M. Koubarakis (Manolis)

    2015-01-01

    textabstractThe linked open data cloud is constantly evolving as datasets get continuously updated with newer versions. As a result, representing, querying, and visualizing the temporal dimension of linked data is crucial. This is especially important for geospatial datasets that form the backbone

  3. SexTant: Visualizing Time-Evolving Linked Geospatial Data

    NARCIS (Netherlands)

    K. Bereta (Konstantina); C. Nikolaou (Charalampos); M. Karpathiotakis (Manos); K. Kyzirakos (Konstantinos); M. Koubarakis (Manolis); E. Blomqvist; T. Groza

    2013-01-01

    htmlabstractWe present SexTant, a Web-based system for the visualization and exploration of time-evolving linked geospatial data and the creation, sharing, and collaborative editing of "temporally-enriched" thematic maps which are produced by combining dierent sources of such data.

  4. Evolving user needs and late-mover advantage

    NARCIS (Netherlands)

    Querbes, Adrien; Frenken, Koen

    2017-01-01

    We propose a generalized NK-model of late-mover advantage where late-mover firms leapfrog first-mover firms as user needs evolve over time. First movers face severe trade-offs between the provision of functionalities in which their products already excel and the additional functionalities requested

  5. Water Footprint Assessment : Evolvement of a New Research Field

    NARCIS (Netherlands)

    Hoekstra, Arjen Y.

    2017-01-01

    This paper reviews the evolvement of water footprint assessment (WFA) as a new research field over the past fifteen years. The research is rooted in four basic thoughts: (1) there is a global dimension to water management because water-intensive commodities are internationally traded, so we must

  6. Evolving information systems: meeting the ever-changing environment

    NARCIS (Netherlands)

    Oei, J.L.H.; Proper, H.A.; Falkenberg, E.D.

    1994-01-01

    To meet the demands of organizations and their ever-changing environment, information systems are required which are able to evolve to the same extent as organizations do. Such a system has to support changes in all time-and application-dependent aspects. In this paper, requirements and a conceptual

  7. Heritage – A Conceptually Evolving and Dissonant Phenomenon ...

    African Journals Online (AJOL)

    I therefore, drawing from literature and experiences gained during field observations and focus group interviews, came up with the idea of working with three viewpoints of heritage. Drawing on real life cases I argue that current heritage management and education practices' failure to recognise and respect the evolving, ...

  8. Baby dumping and evolving baby factories in Nigeria: their ...

    African Journals Online (AJOL)

    Baby dumping and evolving baby factories in Nigeria: their implication for child right and social protection. ... Journal of Religion and Human Relations ... a society-based approach which involves a thorough overhaul of our rigid social orientation which will create room for a conducive environment for child rights and social ...

  9. Evolving Concepts of Development through the Experience of ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... facing developing countries; how thinking has evolved on particular aspects of development; and how different organizations espouse and use ideas to influence development. The edited volume will be submitted to an academic press for publication, along with a companion volume appropriate for university teaching.

  10. Cyperus difformis evolves resistance to propanil

    DEFF Research Database (Denmark)

    Valverde Mena, Bernal Eduardo; Boddy, Louis G.; Pedroso, Rafael M.

    2014-01-01

    Cyperus difformis L. is one of the worst weeds of rice world-wide and has evolved resistance to acetolactate synthase (ALS)-inhibiting herbicides in rice fields of California. Propanil use was intensified to control the widespread resistant biotypes. Rice growers have recently experienced poor co...

  11. Evolutionary genetics: you are what you evolve to eat.

    Science.gov (United States)

    Dworkin, Ian; Jones, Corbin D

    2015-04-20

    The evolution of host specialization can potentially limit future evolutionary opportunities. A new study now shows how Drosophila sechellia, specialized on the toxic Morinda fruit, has evolved new nutritional needs influencing its reproduction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. De Novo Transcriptome Assembly and Sex-Biased Gene Expression in the Cyclical Parthenogenetic Daphnia galeata.

    Science.gov (United States)

    Huylmans, Ann Kathrin; López Ezquerra, Alberto; Parsch, John; Cordellier, Mathilde

    2016-10-23

    Daphnia species have become models for ecological genomics and exhibit interesting features, such as high phenotypic plasticity and a densely packed genome with many lineage-specific genes. They are also cyclic parthenogenetic, with alternating asexual and sexual cycles and environmental sex determination. Here, we present a de novo transcriptome assembly of over 32,000 D. galeata genes and use it to investigate gene expression in females and spontaneously produced males of two clonal lines derived from lakes in Germany and the Czech Republic. We find that only a low percentage (18%) of genes shows sex-biased expression and that there are many more female-biased gene (FBG) than male-biased gene (MBG). Furthermore, FBGs tend to be more conserved between species than MBGs in both sequence and expression. These patterns may be a consequence of cyclic parthenogenesis leading to a relaxation of purifying selection on MBGs. The two clonal lines show considerable differences in both number and identity of sex-biased genes, suggesting that they may have reproductive strategies differing in their investment in sexual reproduction. Orthologs of key genes in the sex determination and juvenile hormone pathways, which are thought to be important for the transition from asexual to sexual reproduction, are present in D. galeata and highly conserved among Daphnia species. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  13. Gene expression profiling in multipotent DFAT cells derived from mature adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ono, Hiromasa [Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510 (Japan); Database Center for Life Science (DBCLS), Research Organization of Information and Systems (ROIS), Faculty of Engineering Bldg.12 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Oki, Yoshinao [Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510 (Japan); Bono, Hidemasa [Database Center for Life Science (DBCLS), Research Organization of Information and Systems (ROIS), Faculty of Engineering Bldg.12 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032 (Japan); Kano, Koichiro, E-mail: kkano@brs.nihon-u.ac.jp [Laboratory of Cell and Tissue Biology, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-8510 (Japan)

    2011-04-15

    Highlights: {yields} Adipocyte dedifferentiation is evident in a significant decrease in typical genes. {yields} Cell proliferation is strongly related to adipocyte dedifferentiation. {yields} Dedifferentiated adipocytes express several lineage-specific genes. {yields} Comparative analyses using publicly available datasets boost the interpretation. -- Abstract: Cellular dedifferentiation signifies the withdrawal of cells from a specific differentiated state to a stem cell-like undifferentiated state. However, the mechanism of dedifferentiation remains obscure. Here we performed comparative transcriptome analyses during dedifferentiation in mature adipocytes (MAs) to identify the transcriptional signatures of multipotent dedifferentiated fat (DFAT) cells derived from MAs. Using microarray systems, we explored similarly expressed as well as significantly differentially expressed genes in MAs during dedifferentiation. This analysis revealed significant changes in gene expression during this process, including a significant reduction in expression of genes for lipid metabolism concomitantly with a significant increase in expression of genes for cell movement, cell migration, tissue developmental processes, cell growth, cell proliferation, cell morphogenesis, altered cell shape, and cell differentiation. Our observations indicate that the transcriptional signatures of DFAT cells derived from MAs are summarized in terms of a significant decrease in functional phenotype-related genes and a parallel increase in cell proliferation, altered cell morphology, and regulation of the differentiation of related genes. A better understanding of the mechanisms involved in dedifferentiation may enable scientists to control and possibly alter the plasticity of the differentiated state, which may lead to benefits not only in stem cell research but also in regenerative medicine.

  14. The SOX family of genes in cancer development: biological relevance and opportunities for therapy.

    Science.gov (United States)

    Castillo, Sandra D; Sanchez-Cespedes, Montse

    2012-09-01

    It has been more that 20 years since the first SOX genes were discovered. Twenty SOX genes have now been identified in mammals and classified into groups with respect to protein identity. SOX family genes code for transcription factors that either activate or repress lineage-specific genes during embryonic development. Furthermore, SOX genes are altered in human genetic syndromes and malignancies, highlighting their involvement in development. This paper reviews the role of SOX genes in embryonic development and human diseases, and describe their involvement in human cancers and possible use in cancer therapeutics. Since most SOX genes behave as oncogenes in many human cancers, their targeting has great therapeutic potential. However, novel specific therapies such as those recently developed against growth factor receptors based on monoclonal antibodies, small inhibitors and even small interfering RNA strategies are difficult to implement for transcriptional factors. Novel strategies are being developed to overcome some of these obstacles. Alternative approaches could indirectly tackle altered SOX genes by exploiting the related molecular networks.

  15. Evolvable mathematical models: A new artificial Intelligence paradigm

    Science.gov (United States)

    Grouchy, Paul

    We develop a novel Artificial Intelligence paradigm to generate autonomously artificial agents as mathematical models of behaviour. Agent/environment inputs are mapped to agent outputs via equation trees which are evolved in a manner similar to Symbolic Regression in Genetic Programming. Equations are comprised of only the four basic mathematical operators, addition, subtraction, multiplication and division, as well as input and output variables and constants. From these operations, equations can be constructed that approximate any analytic function. These Evolvable Mathematical Models (EMMs) are tested and compared to their Artificial Neural Network (ANN) counterparts on two benchmarking tasks: the double-pole balancing without velocity information benchmark and the challenging discrete Double-T Maze experiments with homing. The results from these experiments show that EMMs are capable of solving tasks typically solved by ANNs, and that they have the ability to produce agents that demonstrate learning behaviours. To further explore the capabilities of EMMs, as well as to investigate the evolutionary origins of communication, we develop NoiseWorld, an Artificial Life simulation in which interagent communication emerges and evolves from initially noncommunicating EMM-based agents. Agents develop the capability to transmit their x and y position information over a one-dimensional channel via a complex, dialogue-based communication scheme. These evolved communication schemes are analyzed and their evolutionary trajectories examined, yielding significant insight into the emergence and subsequent evolution of cooperative communication. Evolved agents from NoiseWorld are successfully transferred onto physical robots, demonstrating the transferability of EMM-based AIs from simulation into physical reality.

  16. Evolution and differential expression of a vertebrate vitellogenin gene cluster

    Directory of Open Access Journals (Sweden)

    Kongshaug Heidi

    2009-01-01

    Full Text Available Abstract Background The multiplicity or loss of the vitellogenin (vtg gene family in vertebrates has been argued to have broad implications for the mode of reproduction (placental or non-placental, cleavage pattern (meroblastic or holoblastic and character of the egg (pelagic or benthic. Earlier proposals for the existence of three forms of vertebrate vtgs present conflicting models for their origin and subsequent duplication. Results By integrating phylogenetics of novel vtg transcripts from old and modern teleosts with syntenic analyses of all available genomic variants of non-metatherian vertebrates we identify the gene orthologies between the Sarcopterygii (tetrapod branch and Actinopterygii (fish branch. We argue that the vertebrate vtg gene cluster originated in proto-chromosome m, but that vtg genes have subsequently duplicated and rearranged following whole genome duplications. Sequencing of a novel fourth vtg transcript in labrid species, and the presence of duplicated paralogs in certain model organisms supports the notion that lineage-specific gene duplications frequently occur in teleosts. The data show that the vtg gene cluster is more conserved between acanthomorph teleosts and tetrapods, than in ostariophysan teleosts such as the zebrafish. The differential expression of the labrid vtg genes are further consistent with the notion that neofunctionalized Aa-type vtgs are important determinants of the pelagic or benthic character of the eggs in acanthomorph teleosts. Conclusion The vertebrate vtg gene cluster existed prior to the separation of Sarcopterygii from Actinopterygii >450 million years ago, a period associated with the second round of whole genome duplication. The presence of higher copy numbers in a more highly expressed subcluster is particularly prevalent in teleosts. The differential expression and latent neofunctionalization of vtg genes in acanthomorph teleosts is an adaptive feature associated with oocyte hydration

  17. A Conserved Cytochrome P450 Evolved in Seed Plants Regulates Flower Maturation.

    Science.gov (United States)

    Liu, Zhenhua; Boachon, Benoît; Lugan, Raphaël; Tavares, Raquel; Erhardt, Mathieu; Mutterer, Jérôme; Demais, Valérie; Pateyron, Stéphanie; Brunaud, Véronique; Ohnishi, Toshiyuki; Pencik, Ales; Achard, Patrick; Gong, Fan; Hedden, Peter; Werck-Reichhart, Danièle; Renault, Hugues

    2015-12-07

    Global inspection of plant genomes identifies genes maintained in low copies across taxa and under strong purifying selection, which are likely to have essential functions. Based on this rationale, we investigated the function of the low-duplicated CYP715 cytochrome P450 gene family that appeared early in seed plants and evolved under strong negative selection. Arabidopsis CYP715A1 showed a restricted tissue-specific expression in the tapetum of flower buds and in the anther filaments upon anthesis. cyp715a1 insertion lines showed a strong defect in petal development, and transient alteration of pollen intine deposition. Comparative expression analysis revealed the downregulated expression of genes involved in pollen development, cell wall biogenesis, hormone homeostasis, and floral sesquiterpene biosynthesis, especially TPS21 and several key genes regulating floral development such as MYB21, MYB24, and MYC2. Accordingly, floral sesquiterpene emission was suppressed in the cyp715a1 mutants. Flower hormone profiling, in addition, indicated a modification of gibberellin homeostasis and a strong disturbance of the turnover of jasmonic acid derivatives. Petal growth was partially restored by the active gibberellin GA3 or the functional analog of jasmonoyl-isoleucine, coronatine. CYP715 appears to function as a key regulator of flower maturation, synchronizing petal expansion and volatile emission. It is thus expected to be an important determinant of flower-insect interaction. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  18. Optimizing viral and non-viral gene transfer methods for genetic modification of porcine mesenchymal stem cells

    DEFF Research Database (Denmark)

    Stiehler, Maik; Duch, Mogens R.; Mygind, Tina

    2006-01-01

    and cytokines can induce and maintain lineage-specific differentiation. Due to anatomical and physiological similarities to humans, porcine research models have been proven valuable for the preclinical testing of tissue engineering protocols in large animals. The aim of this study was to evaluate optimized......INTRODUCTION: Mesenchymal stem cells (MSCs) provide an excellent source of pluripotent progenitor cells for tissue-engineering applications due to their proliferation capacity and differentiation potential. Genetic modification of MSCs with genes encoding tissue-specific growth factors...... were evaluated by realtime quantitative RT-PCR and histochemical detection of alkaline phosphatase activity, respectively. RESULTS: Non-viral gene delivery methods resulted in transient eGFP expression by less than 2% of the cells. Using high titer rAAV-based vector up to 90% of the cells were...

  19. FOXP3 gene variations and susceptibility to autism: A case-control study.

    Science.gov (United States)

    Safari, Mohammad Reza; Ghafouri-Fard, Soudeh; Noroozi, Rezvan; Sayad, Arezou; Omrani, Mir Davood; Komaki, Alireza; Eftekharian, Mohammad Mahdi; Taheri, Mohammad

    2017-01-05

    Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental disorders associated with immune system dysregulation. There are supporting evidences for the role of Forkhead Box P3 (FOXP3) gene as a lineage specification factor of regulatory T cells in the pathogenesis of ASD. The aim of this study was to explore possible relationship between genetic variants rs2232365 and rs3761548 of FOXP3 and ASD in 523 ASD patients versus 472 control individuals. Allele frequency analyses showed significant overpresentation of rs2232365-G allele in cases versus controls. In addition, rs2232365 GG genotype was associated with ASD in dominant inheritance model. Haplotype analysis revealed no significant association of any estimated block of rs2232365/rs3761548 with ASD. Our study indicated that rs2232365 is associated with ASD. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. The Dynamical Classification of Centaurs which Evolve into Comets

    Science.gov (United States)

    Wood, Jeremy R.; Horner, Jonathan; Hinse, Tobias; Marsden, Stephen; Swinburne University of Technology

    2016-10-01

    Centaurs are small Solar system bodies with semi-major axes between Jupiter and Neptune and perihelia beyond Jupiter. Centaurs can be further subclassified into two dynamical categories - random walk and resonance hopping. Random walk Centaurs have mean square semi-major axes () which vary in time according to a generalized diffusion equation where ~t2H. H is the Hurst exponent with 0 for resonance hopping Centaurs is not well described by generalized diffusion.The aim of this study is to determine which dynamical type of Centaur is most likely to evolve into each class of comet. 31,722 fictional massless test particles were integrated for 3 Myr in the 6-body problem (Sun, Jovian planets, test particle). Initially each test particle was a member of one of four groups. The semi-major axes of all test particles in a group were clustered within 0.27 au from a first order, interior Mean Motion resonance of Neptune. The resonances were centered at 18.94 au, 22.95 au, 24.82 au and 28.37 au.If the perihelion of a test particle reached particle was considered to be a comet and classified as either a random walk or resonance hopping Centaur. The results showed that over 4,000 test particles evolved into comets within 3 Myr. 59% of these test particles were random walk and 41% were resonance hopping. The behavior of the semi-major axis in time was usually well described by generalized diffusion for random walk Centaurs (ravg = 0.98) and poorly described for resonance hopping Centaurs (ravg = 0.52). The average Hurst exponent was 0.48 for random walk Centaurs and 0.20 for resonance hopping Centaurs. Random walk Centaurs were more likely to evolve into short period comets while resonance hopping Centaurs were more likely to evolve into long period comets. For each initial cluster, resonance hopping Centaurs took longer to evolve into comets than random walk Centaurs. Overall the population of random walk Centaurs averaged 143 kyr to evolve into comets, and the population of

  1. Genic regions of a large salamander genome contain long introns and novel genes

    Directory of Open Access Journals (Sweden)

    Bryant Susan V

    2009-01-01

    Full Text Available Abstract Background The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 × 109 bp were isolated and sequenced to characterize the structure of genic regions. Results Annotation of genes within BACs showed that axolotl introns are on average 10× longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin metamorphosis. Unexpectedly, a third novel gene was also discovered while manually annotating BACs. Analysis of human-axolotl protein-coding sequences suggests there are 2% more lineage specific genes in the axolotl genome than the human genome, but the great majority (86% of genes between axolotl and human are predicted to be 1:1 orthologs. Considering that axolotl genes are on average 5× larger than human genes, the genic component of the salamander genome is estimated to be incredibly large, approximately 2.8 gigabases! Conclusion This study shows that a large salamander genome has a correspondingly large genic component, primarily because genes have incredibly long introns. These intronic sequences may harbor novel coding and non-coding sequences that regulate biological processes that are unique to salamanders.

  2. Expansion by whole genome duplication and evolution of the sox gene family in teleost fish.

    Science.gov (United States)

    Voldoire, Emilien; Brunet, Frédéric; Naville, Magali; Volff, Jean-Nicolas; Galiana, Delphine

    2017-01-01

    It is now recognized that several rounds of whole genome duplication (WGD) have occurred during the evolution of vertebrates, but the link between WGDs and phenotypic diversification remains unsolved. We have investigated in this study the impact of the teleost-specific WGD on the evolution of the sox gene family in teleostean fishes. The sox gene family, which encodes for transcription factors, has essential role in morphology, physiology and behavior of vertebrates and teleosts, the current largest group of vertebrates. We have first redrawn the evolution of all sox genes identified in eleven teleost genomes using a comparative genomic approach including phylogenetic and synteny analyses. We noticed, compared to tetrapods, an important expansion of the sox family: 58% (11/19) of sox genes are duplicated in teleost genomes. Furthermore, all duplicated sox genes, except sox17 paralogs, are derived from the teleost-specific WGD. Then, focusing on five sox genes, analyzing the evolution of coding and non-coding sequences, as well as the expression patterns in fish embryos and adult tissues, we demonstrated that these paralogs followed lineage-specific evolutionary trajectories in teleost genomes. This work, based on whole genome data from multiple teleostean species, supports the contribution of WGDs to the expansion of gene families, as well as to the emergence of genomic differences between lineages that might promote genetic and phenotypic diversity in teleosts.

  3. Phylogenomic detection and functional prediction of genes potentially important for plant meiosis.

    Science.gov (United States)

    Zhang, Luoyan; Kong, Hongzhi; Ma, Hong; Yang, Ji

    2018-02-15

    Meiosis is a specialized type of cell division necessary for sexual reproduction in eukaryotes. A better understanding of the cytological procedures of meiosis has been achieved by comprehensive cytogenetic studies in plants, while the genetic mechanisms regulating meiotic progression remain incompletely understood. The increasing accumulation of complete genome sequences and large-scale gene expression datasets has provided a powerful resource for phylogenomic inference and unsupervised identification of genes involved in plant meiosis. By integrating sequence homology and expression data, 164, 131, 124 and 162 genes potentially important for meiosis were identified in the genomes of Arabidopsis thaliana, Oryza sativa, Selaginella moellendorffii and Pogonatum aloides, respectively. The predicted genes were assigned to 45 meiotic GO terms, and their functions were related to different processes occurring during meiosis in various organisms. Most of the predicted meiotic genes underwent lineage-specific duplication events during plant evolution, with about 30% of the predicted genes retaining only a single copy in higher plant genomes. The results of this study provided clues to design experiments for better functional characterization of meiotic genes in plants, promoting the phylogenomic approach to the evolutionary dynamics of the plant meiotic machineries. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Large-Scale Evolutionary Analysis of Genes and Supergene Clusters from Terpenoid Modular Pathways Provides Insights into Metabolic Diversification in Flowering Plants

    Science.gov (United States)

    Hofberger, Johannes A.; Ramirez, Aldana M.; van den Bergh, Erik; Zhu, Xinguang; Bouwmeester, Harro J.; Schuurink, Robert C.; Schranz, M. Eric

    2015-01-01

    An important component of plant evolution is the plethora of pathways producing more than 200,000 biochemically diverse specialized metabolites with pharmacological, nutritional and ecological significance. To unravel dynamics underlying metabolic diversification, it is critical to determine lineage-specific gene family expansion in a phylogenomics framework. However, robust functional annotation is often only available for core enzymes catalyzing committed reaction steps within few model systems. In a genome informatics approach, we extracted information from early-draft gene-space assemblies and non-redundant transcriptomes to identify protein families involved in isoprenoid biosynthesis. Isoprenoids comprise terpenoids with various roles in plant-environment interaction, such as pollinator attraction or pathogen defense. Combining lines of evidence provided by synteny, sequence homology and Hidden-Markov-Modelling, we screened 17 genomes including 12 major crops and found evidence for 1,904 proteins associated with terpenoid biosynthesis. Our terpenoid genes set contains evidence for 840 core terpene-synthases and 338 triterpene-specific synthases. We further identified 190 prenyltransferases, 39 isopentenyl-diphosphate isomerases as well as 278 and 219 proteins involved in mevalonate and methylerithrol pathways, respectively. Assessing the impact of gene and genome duplication to lineage-specific terpenoid pathway expansion, we illustrated key events underlying terpenoid metabolic diversification within 250 million years of flowering plant radiation. By quantifying Angiosperm-wide versatility and phylogenetic relationships of pleiotropic gene families in terpenoid modular pathways, our analysis offers significant insight into evolutionary dynamics underlying diversification of plant secondary metabolism. Furthermore, our data provide a blueprint for future efforts to identify and more rapidly clone terpenoid biosynthetic genes from any plant species. PMID

  5. Large-Scale Evolutionary Analysis of Genes and Supergene Clusters from Terpenoid Modular Pathways Provides Insights into Metabolic Diversification in Flowering Plants.

    Science.gov (United States)

    Hofberger, Johannes A; Ramirez, Aldana M; Bergh, Erik van den; Zhu, Xinguang; Bouwmeester, Harro J; Schuurink, Robert C; Schranz, M Eric

    2015-01-01

    An important component of plant evolution is the plethora of pathways producing more than 200,000 biochemically diverse specialized metabolites with pharmacological, nutritional and ecological significance. To unravel dynamics underlying metabolic diversification, it is critical to determine lineage-specific gene family expansion in a phylogenomics framework. However, robust functional annotation is often only available for core enzymes catalyzing committed reaction steps within few model systems. In a genome informatics approach, we extracted information from early-draft gene-space assemblies and non-redundant transcriptomes to identify protein families involved in isoprenoid biosynthesis. Isoprenoids comprise terpenoids with various roles in plant-environment interaction, such as pollinator attraction or pathogen defense. Combining lines of evidence provided by synteny, sequence homology and Hidden-Markov-Modelling, we screened 17 genomes including 12 major crops and found evidence for 1,904 proteins associated with terpenoid biosynthesis. Our terpenoid genes set contains evidence for 840 core terpene-synthases and 338 triterpene-specific synthases. We further identified 190 prenyltransferases, 39 isopentenyl-diphosphate isomerases as well as 278 and 219 proteins involved in mevalonate and methylerithrol pathways, respectively. Assessing the impact of gene and genome duplication to lineage-specific terpenoid pathway expansion, we illustrated key events underlying terpenoid metabolic diversification within 250 million years of flowering plant radiation. By quantifying Angiosperm-wide versatility and phylogenetic relationships of pleiotropic gene families in terpenoid modular pathways, our analysis offers significant insight into evolutionary dynamics underlying diversification of plant secondary metabolism. Furthermore, our data provide a blueprint for future efforts to identify and more rapidly clone terpenoid biosynthetic genes from any plant species.

  6. The Evolving Role of Emergency Departments in the United States.

    Science.gov (United States)

    Morganti, Kristy Gonzalez; Bauhoff, Sebastian; Blanchard, Janice C; Abir, Mahshid; Iyer, Neema; Smith, Alexandria; Vesely, Joseph V; Okeke, Edward N; Kellermann, Arthur L

    2013-01-01

    The research described in this article was performed to develop a more complete picture of how hospital emergency departments (EDs) contribute to the U.S. health care system, which is currently evolving in response to economic, clinical, and political pressures. Using a mix of quantitative and qualitative methods, it explores the evolving role that EDs and the personnel who staff them play in evaluating and managing complex and high-acuity patients, serving as the key decisionmaker for roughly half of all inpatient hospital admissions, and serving as "the safety net of the safety net" for patients who cannot get care elsewhere. The report also examines the role that EDs may soon play in either contributing to or helping to control the rising costs of health care.

  7. AUTOMOTIVE APPLICATIONS OF EVOLVING TAKAGI-SUGENO-KANG FUZZY MODELS

    Directory of Open Access Journals (Sweden)

    Radu-Emil Precup

    2017-08-01

    Full Text Available This paper presents theoretical and application results concerning the development of evolving Takagi-Sugeno-Kang fuzzy models for two dynamic systems, which will be viewed as controlled processes, in the field of automotive applications. The two dynamic systems models are nonlinear dynamics of the longitudinal slip in the Anti-lock Braking Systems (ABS and the vehicle speed in vehicles with the Continuously Variable Transmission (CVT systems. The evolving Takagi-Sugeno-Kang fuzzy models are obtained as discrete-time fuzzy models by incremental online identification algorithms. The fuzzy models are validated against experimental results in the case of the ABS and the first principles simulation results in the case of the vehicle with the CVT.

  8. Duplication Detection When Evolving Feature Models of Software Product Lines

    Directory of Open Access Journals (Sweden)

    Amal Khtira

    2015-10-01

    Full Text Available After the derivation of specific applications from a software product line, the applications keep evolving with respect to new customer’s requirements. In general, evolutions in most industrial projects are expressed using natural language, because it is the easiest and the most flexible way for customers to express their needs. However, the use of this means of communication has shown its limits in detecting defects, such as inconsistency and duplication, when evolving the existing models of the software product line. The aim of this paper is to transform the natural language specifications of new evolutions into a more formal representation using natural language processing. Then, an algorithm is proposed to automatically detect duplication between these specifications and the existing product line feature models. In order to instantiate the proposed solution, a tool is developed to automatize the two operations.

  9. Real-time evolvable pulse shaper for radiation measurements

    Energy Technology Data Exchange (ETDEWEB)

    Lanchares, Juan, E-mail: julandan@dacya.ucm.es [Facultad de Informática, Universidad Complutense de Madrid (UCM), C/Prof. José García Santesmases s/n, 28040 Madrid (Spain); Garnica, Oscar, E-mail: ogarnica@dacya.ucm.es [Facultad de Informática, Universidad Complutense de Madrid (UCM), C/Prof. José García Santesmases s/n, 28040 Madrid (Spain); Risco-Martín, José L., E-mail: jlrisco@dacya.ucm.es [Facultad de Informática, Universidad Complutense de Madrid (UCM), C/Prof. José García Santesmases s/n, 28040 Madrid (Spain); Ignacio Hidalgo, J., E-mail: hidalgo@dacya.ucm.es [Facultad de Informática, Universidad Complutense de Madrid (UCM), C/Prof. José García Santesmases s/n, 28040 Madrid (Spain); Regadío, Alberto, E-mail: alberto.regadio@insa.es [Área de Tecnologías Electrónicas, Instituto Nacional de Técnica Aeroespacial (INTA), 28850 Torrejón de Ardoz, Madrid (Spain)

    2013-11-01

    In the last two decades, recursive algorithms for real-time digital pulse shaping in pulse height measurements have been developed and published in number of articles and textbooks. All these algorithms try to synthesize in real time optimum or near optimum shapes in the presence of noise. Even though some of these shapers can be considered effective designs, some side effects like aging cannot be ignored. We may observe that after sensors degradation, the signal obtained is not valid. In this regard, we present in this paper a novel technique that, based on evolvable hardware concepts, is able to evolve the degenerated shaper into a new design with better performance than the original one under the new sensor features.

  10. Exploring, exploiting and evolving diversity of aquatic ecosystem models

    DEFF Research Database (Denmark)

    Janssen, Annette B. G.; Arhonditsis, George B.; Beusen, Arthur

    2015-01-01

    Here, we present a community perspective on how to explore, exploit and evolve the diversity in aquatic ecosystem models. These models play an important role in understanding the functioning of aquatic ecosystems, filling in observation gaps and developing effective strategies for water quality...... management. In this spirit, numerous models have been developed since the 1970s. We set off to explore model diversity by making an inventory among 42 aquatic ecosystem modellers, by categorizing the resulting set of models and by analysing them for diversity. We then focus on how to exploit model diversity...... by comparing and combining different aspects of existing models. Finally, we discuss how model diversity came about in the past and could evolve in the future. Throughout our study, we use analogies from biodiversity research to analyse and interpret model diversity. We recommend to make models publicly...

  11. E Unibus Plurum: genomic analysis of an experimentally evolved polymorphism in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Margie A Kinnersley

    2009-11-01

    Full Text Available Microbial populations founded by a single clone and propagated under resource limitation can become polymorphic. We sought to elucidate genetic mechanisms whereby a polymorphism evolved in Escherichia coli under glucose limitation and persisted because of cross-feeding among multiple adaptive clones. Apart from a 29 kb deletion in the dominant clone, no large-scale genomic changes distinguished evolved clones from their common ancestor. Using transcriptional profiling on co-evolved clones cultured separately under glucose-limitation we identified 180 genes significantly altered in expression relative to the common ancestor grown under similar conditions. Ninety of these were similarly expressed in all clones, and many of the genes affected (e.g., mglBAC, mglD, and lamB are in operons coordinately regulated by CRP and/or rpoS. While the remaining significant expression differences were clone-specific, 93% were exhibited by the majority clone, many of which are controlled by global regulators, CRP and CpxR. When transcriptional profiling was performed on adaptive clones cultured together, many expression differences that distinguished the majority clone cultured in isolation were absent, suggesting that CpxR may be activated by overflow metabolites removed by cross-feeding strains in co-culture. Relative to their common ancestor, shared expression differences among adaptive clones were partly attributable to early-arising shared mutations in the trans-acting global regulator, rpoS, and the cis-acting regulator, mglO. Gene expression differences that distinguished clones may in part be explained by mutations in trans-acting regulators malT and glpK, and in cis-acting sequences of acs. In the founder, a cis-regulatory mutation in acs (acetyl CoA synthetase and a structural mutation in glpR (glycerol-3-phosphate repressor likely favored evolution of specialists that thrive on overflow metabolites. Later-arising mutations that led to specialization

  12. The Use of Genetic Programming to Evolve Passive Filter Circuits

    OpenAIRE

    Ogri J. Ushie; Abbod, Maysam F.; Julie C. Ogbulezie

    2017-01-01

    This paper introduces the use of Genetic Programming (GP), Genetic Folding and symbolic circuit analysis in Matlab for the evolution of passive filter circuits. Instead of combining MATLAB and PSPICE in electronic circuit simulation, in this work, only MATLAB is used. It helps to reduce elapsed time for transferring the simulation between the two software packages. The circuit evolved from GP using the Matlab program and is automatically converted into a symbolic netlist also by using a Matla...

  13. Evolving Pacing Strategies for Team Pursuit Track Cycling

    OpenAIRE

    Wagner, Markus; Day, Jareth; Jordan, Diora; Kroeger, Trent; Neumann, Frank

    2011-01-01

    Team pursuit track cycling is a bicycle racing sport held on velodromes and is part of the Summer Olympics. It involves the use of strategies to minimize the overall time that a team of cyclists needs to complete a race. We present an optimisation framework for team pursuit track cycling and show how to evolve strategies using metaheuristics for this interesting real-world problem. Our experimental results show that these heuristics lead to significantly better strategies than state-of-art st...

  14. ONMCGP: Orthogonal Neighbourhood Mutation Cartesian Genetic Programming for Evolvable Hardware

    Science.gov (United States)

    I, Fuchuan N.; I, Yuanxiang L.; E, Peng K.

    2014-03-01

    Evolvable Hardware is facing the problems of scalability and stalling effect. This paper proposed a novel Orthogonal Neighbourhood Mutation (ONM) operator in Cartesian genetic programming (CGP), to reduce the stalling effect in CGP and improve the efficiency of the algorithms.The method incorporates with Differential Evolution strategy. Demonstrated by experiments on benchmark, the proposed Orthogonal Neighbourhood Search can jump out of Local optima, reduce the stalling effect in CGP and the algorithm convergence faster.

  15. A Rapidly Evolving Active Region NOAA 8032 observed on April ...

    Indian Academy of Sciences (India)

    1997-04-15

    The active region NOAA 8032 of April 15, 1997 was observed to evolve rapidly. The GOES X-ray data showed a number of sub-flares and two C-class flares during the 8-9 hours of its evolution. The magnetic evolution of this region is studied to ascertain its role in flare production. Large changes were observed in magnetic ...

  16. Engineering Therapies that Evolve to Autonomously Control Epidemics

    Science.gov (United States)

    2017-06-01

    FINAL TECHNICAL REPORT Grant No. D15AP00024 “ Engineering Therapies that Evolve to Autonomously Control Epidemics” PI: Leor Weinberger...viruses could be engineered into therapeutics, known as Therapeutic Interfering Particles (’TIPs’), using the virus HIV as a model system. By engineering ... engineered TIPs could have indefinite, population-scale impact. To achieve this aim, we developed novel multi-scale models that connected the measured

  17. india's northward drift and collision with asia: evolving faunal response

    Indian Academy of Sciences (India)

    INDIA'S NORTHWARD DRIFT AND COLLISION WITH ASIA: EVOLVING FAUNAL RESPONSE · Slide 2 · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19 · Slide 20 · Slide 21 · Slide 22 · Slide 23 · Slide 24.

  18. New nuclear build and evolving radiation protection challenges.

    Science.gov (United States)

    Lazo, Edward

    2011-01-01

    Radiological protection has continued to evolve in order to meet emerging challenges and will continue to do so. This paper will discuss the scientific and social challenges that will or may be faced by the radiological protection community in the coming 10 to 20 y and how these may affect what is expected to be a renewed interest in building and operating nuclear power plants for electricity generation. Copyright © 2010 Health Physics Society

  19. TRICARE Policy and Operations: Evolving to Support the Quadruple Aim

    Science.gov (United States)

    2011-01-24

    Examples of Evolution – TRICARE in Alaska – Autism Services Demonstration 2011 MHS Conference 3 Track L  Evolving to achieve the Quadruple Aim...Heidelberg MEDDAC Lessons Learned 1, 2, 3, 4 1, 2, 3, 4 2 a. TRICARE in Alaska b. Autism Services Demonstration c. A Regional View 3 1 1, 2...3, 4 3 TRICARE Pharmacy Programs 3, 4 4 TRICARE for Reserves and National Guard 1, 2, 3 5 TRICARE Dental Programs 1, 2, 4 6 a

  20. Establishing credibility: Evolving perceptions of the European Central Bank

    OpenAIRE

    Linda S. Goldberg; Klein, Michael W

    2005-01-01

    The credibility of a central bank’s anti-inflation stance, a key determinant of its success, may reflect institutional structure or, more dynamically, the history of policy decisions. The first years of the European Central Bank (ECB) provide a natural experiment for considering whether, and how, central bank credibility evolves. In this paper, we present a model demonstrating how the high-frequency response of asset prices to news reflects market perceptions of the anti-inflation stance of a...

  1. Hemicrania continua evolving from cluster headache responsive to valproic acid.

    Science.gov (United States)

    Lambru, Giorgio; Castellini, Paola; Bini, Annamaria; Evangelista, Andrea; Manzoni, Gian Camillo; Torelli, Paola

    2008-10-01

    Hemicrania continua (HC) is a rare type of primary headache characterized by a prompt and enduring response to indomethacin. We describe a patient who suffered from cluster headache evolving into ipsilateral HC, who does not tolerate a long-term indomethacin therapy. The case was complex in terms of diagnosis, associated comorbidity, and choice of treatment; after several trials with different therapeutic regimens, we started the patient on a therapy with valproic acid and obtained an improvement of her HC.

  2. A weighted network evolving model with capacity constraints

    Science.gov (United States)

    Wu, XiaoHuan; Zhu, JinFu; Wu, WeiWei; Ge, Wei

    2013-09-01

    Most of existing works on complex network assumed that the nodes and edges were uncapacitated during the evolving process, and displayed "rich club" phenomenon. Here we will show that the "rich club" could be changed to "common rich" if we consider the node capacity. In this paper, we define the node and edge attractive index with node capacity, and propose a new evolving model on the base of BBV model, with evolving simulations of the networks. In the new model, an entering node is linked with an existing node according to the preferential attachment mechanism defined with the attractive index of the existing node. We give the theoretical approximation and simulation solutions. If node capacity is finite, the rich node may not be richer further when the node strength approaches or gets to the node capacity. This is confirmed by analyzing the passenger traffic and routes of Chinese main airports. Due to node strength being function of time t, we can use the theoretical approximation solution to forecast how node strength changes and the time when node strength reaches its maximum value.

  3. Social networks: Evolving graphs with memory dependent edges

    Science.gov (United States)

    Grindrod, Peter; Parsons, Mark

    2011-10-01

    The plethora of digital communication technologies, and their mass take up, has resulted in a wealth of interest in social network data collection and analysis in recent years. Within many such networks the interactions are transient: thus those networks evolve over time. In this paper we introduce a class of models for such networks using evolving graphs with memory dependent edges, which may appear and disappear according to their recent history. We consider time discrete and time continuous variants of the model. We consider the long term asymptotic behaviour as a function of parameters controlling the memory dependence. In particular we show that such networks may continue evolving forever, or else may quench and become static (containing immortal and/or extinct edges). This depends on the existence or otherwise of certain infinite products and series involving age dependent model parameters. We show how to differentiate between the alternatives based on a finite set of observations. To test these ideas we show how model parameters may be calibrated based on limited samples of time dependent data, and we apply these concepts to three real networks: summary data on mobile phone use from a developing region; online social-business network data from China; and disaggregated mobile phone communications data from a reality mining experiment in the US. In each case we show that there is evidence for memory dependent dynamics, such as that embodied within the class of models proposed here.

  4. Biomimetic molecular design tools that learn, evolve, and adapt.

    Science.gov (United States)

    Winkler, David A

    2017-01-01

    A dominant hallmark of living systems is their ability to adapt to changes in the environment by learning and evolving. Nature does this so superbly that intensive research efforts are now attempting to mimic biological processes. Initially this biomimicry involved developing synthetic methods to generate complex bioactive natural products. Recent work is attempting to understand how molecular machines operate so their principles can be copied, and learning how to employ biomimetic evolution and learning methods to solve complex problems in science, medicine and engineering. Automation, robotics, artificial intelligence, and evolutionary algorithms are now converging to generate what might broadly be called in silico-based adaptive evolution of materials. These methods are being applied to organic chemistry to systematize reactions, create synthesis robots to carry out unit operations, and to devise closed loop flow self-optimizing chemical synthesis systems. Most scientific innovations and technologies pass through the well-known "S curve", with slow beginning, an almost exponential growth in capability, and a stable applications period. Adaptive, evolving, machine learning-based molecular design and optimization methods are approaching the period of very rapid growth and their impact is already being described as potentially disruptive. This paper describes new developments in biomimetic adaptive, evolving, learning computational molecular design methods and their potential impacts in chemistry, engineering, and medicine.

  5. Biomimetic molecular design tools that learn, evolve, and adapt

    Directory of Open Access Journals (Sweden)

    David A Winkler

    2017-06-01

    Full Text Available A dominant hallmark of living systems is their ability to adapt to changes in the environment by learning and evolving. Nature does this so superbly that intensive research efforts are now attempting to mimic biological processes. Initially this biomimicry involved developing synthetic methods to generate complex bioactive natural products. Recent work is attempting to understand how molecular machines operate so their principles can be copied, and learning how to employ biomimetic evolution and learning methods to solve complex problems in science, medicine and engineering. Automation, robotics, artificial intelligence, and evolutionary algorithms are now converging to generate what might broadly be called in silico-based adaptive evolution of materials. These methods are being applied to organic chemistry to systematize reactions, create synthesis robots to carry out unit operations, and to devise closed loop flow self-optimizing chemical synthesis systems. Most scientific innovations and technologies pass through the well-known “S curve”, with slow beginning, an almost exponential growth in capability, and a stable applications period. Adaptive, evolving, machine learning-based molecular design and optimization methods are approaching the period of very rapid growth and their impact is already being described as potentially disruptive. This paper describes new developments in biomimetic adaptive, evolving, learning computational molecular design methods and their potential impacts in chemistry, engineering, and medicine.

  6. Fuzzily Connected Multimodel Systems Evolving Autonomously From Data Streams.

    Science.gov (United States)

    Angelov, P

    2011-08-01

    A general framework and a holistic concept are proposed in this paper that combine computationally light machine learning from streaming data with the online identification and adaptation of dynamic systems in regard to their structure and parameters. According to this concept, the system is assumed to be decomposable into a set of fuzzily connected simple local models. The main thrust of this paper is in the development of an original approach for the self-design, self-monitoring, self-management, and self-learning of such systems in a dynamic manner from data streams which automatically detect and react to the shift in the data distribution by evolving the system structure. Novelties of this contribution lie in the following: 1) the computationally simple approach (simpl_e_Clustering-simplified evolving Clustering) to data space partitioning by recursive evolving clustering based on the relative position of the new data sample to the mean of the overall data, 2) the learning technique for online structure evolution as a reaction to the shift in the data distribution, 3) the method for online system structure simplification based on utility and inputs/feature selection, and 4) the novel graphical illustration of the spatiotemporal evolution of the data stream. The application domain for this computationally efficient technique ranges from clustering, modeling, prognostics, classification, and time-series prediction to pattern recognition, image segmentation, vector quantization, etc., to more general problems in various application areas, e.g., intelligent sensors, mobile robotics, advanced manufacturing processes, etc.

  7. Evolving Human Alteration of the Carbon Cycle: the Watershed Continuum

    Science.gov (United States)

    Kaushal, S.; Delaney Newcomb, K.; Newcomer Johnson, T.; Pennino, M. J.; Smith, R. M.; Beaulieu, J. J.; Belt, K.; Grese, M.; Blomquist, J.; Duan, S.; Findlay, S.; Likens, G.; Mayer, P. M.; Murthy, S.; Utz, R.; Yepsen, M.

    2014-12-01

    Watersheds experiencing land development are constantly evolving, and their biogeochemical signatures are expected to evolve across both space and time in drainage waters. We investigate how land development influences spatial and temporal evolution of the carbon cycle from small streams to major rivers in the Eastern U.S. Along the watershed continuum, we show that there is spatial evolution in: (1) the amount, chemical form, and bioavailability of carbon; (2) carbon retention/release at the reach scale; and (3) ecosystem metabolism of carbon from headwaters to coastal waters. Over shorter time scales, the interaction between land use and climate variability alters magnitude and frequency of carbon "pulses" in watersheds. Amounts and forms of carbon pulses in agricultural and urban watersheds respond similarly to climate variability due to headwater alteration and loss of ecosystem services to buffer runoff and temperature changes. Over longer time scales, land use change has altered organic carbon concentrations in tidal waters of Chesapeake Bay, and there have been increased bicarbonate alkalinity concentrations in rivers throughout the Eastern U.S. due to human activities. In summary, our analyses indicates that the form and reactivity of carbon have evolved over space and time along the watershed continuum with major implications for downstream ecosystem metabolism, biological oxygen demand, carbon dioxide production, and river alkalinization.

  8. Higher rates of sex evolve in spatially heterogeneous environments.

    Science.gov (United States)

    Becks, Lutz; Agrawal, Aneil F

    2010-11-04

    The evolution and maintenance of sexual reproduction has puzzled biologists for decades. Although this field is rich in hypotheses, experimental evidence is scarce. Some important experiments have demonstrated differences in evolutionary rates between sexual and asexual populations; other experiments have documented evolutionary changes in phenomena related to genetic mixing, such as recombination and selfing. However, direct experiments of the evolution of sex within populations are extremely rare (but see ref. 12). Here we use the rotifer, Brachionus calyciflorus, which is capable of both sexual and asexual reproduction, to test recent theory predicting that there is more opportunity for sex to evolve in spatially heterogeneous environments. Replicated experimental populations of rotifers were maintained in homogeneous environments, composed of either high- or low-quality food habitats, or in heterogeneous environments that consisted of a mix of the two habitats. For populations maintained in either type of homogeneous environment, the rate of sex evolves rapidly towards zero. In contrast, higher rates of sex evolve in populations experiencing spatially heterogeneous environments. The data indicate that the higher level of sex observed under heterogeneity is not due to sex being less costly or selection against sex being less efficient; rather sex is sufficiently advantageous in heterogeneous environments to overwhelm its inherent costs. Counter to some alternative theories for the evolution of sex, there is no evidence that genetic drift plays any part in the evolution of sex in these populations.

  9. The Pyrolysis Behavior of Evolved Species from Date Palm Seeds

    Directory of Open Access Journals (Sweden)

    Babiker Mohammed Elamen

    2014-07-01

    Full Text Available The pyrolytic behavior of evolved gases from date palm seeds (DPSs were measured to gain insight into the mechanism of DPSs pyrolysis. Six different cultivars were used in this study, namely Deglet nour, Piarom, Suffry, Safawi, Mabroom and Aliya. A thermo-gravimetric analyzer (TGA and a real-time gas analyzer (GA were used to calculate the mass losses and the mole fraction of evolved gases, respectively. DPSs samples were pyrolyzed in an inert atmosphere condition using argon with a purge rate of 100 mL/minute. The samples were subjected to non-isothermal operation. An independent single model and parallel reaction model were adopted to interpret the empirical data collected from TGA and GA, respectively. The results reveled that there are three types of pyrolysis zones depending on the main constituents of every cultivars. Moreover, the potentialty of the zones in controlling the pyrolysis behavior was noticeable. The dominant hydrocarbon species in DPSs were CO and CH4 (40 to 50% higher than the rest of species. The mole fraction of CO was 2 to 4 times higher than the mole fraction of CO2. The activation energy and frequency factor of DPSs evolved species showed that Mabroom has the highest activation energy regarding H2 (63.21kJ/mol and CO (74.32 kJ/mol.

  10. Biomimetic molecular design tools that learn, evolve, and adapt

    Science.gov (United States)

    2017-01-01

    A dominant hallmark of living systems is their ability to adapt to changes in the environment by learning and evolving. Nature does this so superbly that intensive research efforts are now attempting to mimic biological processes. Initially this biomimicry involved developing synthetic methods to generate complex bioactive natural products. Recent work is attempting to understand how molecular machines operate so their principles can be copied, and learning how to employ biomimetic evolution and learning methods to solve complex problems in science, medicine and engineering. Automation, robotics, artificial intelligence, and evolutionary algorithms are now converging to generate what might broadly be called in silico-based adaptive evolution of materials. These methods are being applied to organic chemistry to systematize reactions, create synthesis robots to carry out unit operations, and to devise closed loop flow self-optimizing chemical synthesis systems. Most scientific innovations and technologies pass through the well-known “S curve”, with slow beginning, an almost exponential growth in capability, and a stable applications period. Adaptive, evolving, machine learning-based molecular design and optimization methods are approaching the period of very rapid growth and their impact is already being described as potentially disruptive. This paper describes new developments in biomimetic adaptive, evolving, learning computational molecular design methods and their potential impacts in chemistry, engineering, and medicine. PMID:28694872

  11. Evolving spiking neural networks: a novel growth algorithm exhibits unintelligent design

    Science.gov (United States)

    Schaffer, J. David

    2015-06-01

    Spiking neural networks (SNNs) have drawn considerable excitement because of their computational properties, believed to be superior to conventional von Neumann machines, and sharing properties with living brains. Yet progress building these systems has been limited because we lack a design methodology. We present a gene-driven network growth algorithm that enables a genetic algorithm (evolutionary computation) to generate and test SNNs. The genome for this algorithm grows O(n) where n is the number of neurons; n is also evolved. The genome not only specifies the network topology, but all its parameters as well. Experiments show the algorithm producing SNNs that effectively produce a robust spike bursting behavior given tonic inputs, an application suitable for central pattern generators. Even though evolution did not include perturbations of the input spike trains, the evolved networks showed remarkable robustness to such perturbations. In addition, the output spike patterns retain evidence of the specific perturbation of the inputs, a feature that could be exploited by network additions that could use this information for refined decision making if required. On a second task, a sequence detector, a discriminating design was found that might be considered an example of "unintelligent design"; extra non-functional neurons were included that, while inefficient, did not hamper its proper functioning.

  12. Effective but costly, evolved mechanisms of defense against a virulent opportunistic pathogen in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Yixin H Ye

    2009-04-01

    Full Text Available Drosophila harbor substantial genetic variation for antibacterial defense, and investment in immunity is thought to involve a costly trade-off with life history traits, including development, life span, and reproduction. To understand the way in which insects invest in fighting bacterial infection, we selected for survival following systemic infection with the opportunistic pathogen Pseudomonas aeruginosa in wild-caught Drosophila melanogaster over 10 generations. We then examined genome-wide changes in expression in the selected flies relative to unselected controls, both of which had been infected with the pathogen. This powerful combination of techniques allowed us to specifically identify the genetic basis of the evolved immune response. In response to selection, population-level survivorship to infection increased from 15% to 70%. The evolved capacity for defense was costly, however, as evidenced by reduced longevity and larval viability and a rapid loss of the trait once selection pressure was removed. Counter to expectation, we observed more rapid developmental rates in the selected flies. Selection-associated changes in expression of genes with dual involvement in developmental and immune pathways suggest pleiotropy as a possible mechanism for the positive correlation. We also found that both the Toll and the Imd pathways work synergistically to limit infectivity and that cellular immunity plays a more critical role in overcoming P. aeruginosa infection than previously reported. This work reveals novel pathways by which Drosophila can survive infection with a virulent pathogen that may be rare in wild populations, however, due to their cost.

  13. On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks.

    Directory of Open Access Journals (Sweden)

    Paul Tonelli

    Full Text Available A major goal of bio-inspired artificial intelligence is to design artificial neural networks with abilities that resemble those of animal nervous systems. It is commonly believed that two keys for evolving nature-like artificial neural networks are (1 the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks, and (2 synaptic plasticity, which allows neural networks to change during their lifetime. So far, these two topics have been mainly studied separately. The present paper shows that they are actually deeply connected. Using a simple operant conditioning task and a classic evolutionary algorithm, we compare three ways to encode plastic neural networks: a direct encoding, a developmental encoding inspired by computational neuroscience models, and a developmental encoding inspired by morphogen gradients (similar to HyperNEAT. Our results suggest that using a developmental encoding could improve the learning abilities of evolved, plastic neural networks. Complementary experiments reveal that this result is likely the consequence of the bias of developmental encodings towards regular structures: (1 in our experimental setup, encodings that tend to produce more regular networks yield networks with better general learning abilities; (2 whatever the encoding is, networks that are the more regular are statistically those that have the best learning abilities.

  14. Measuring the Accuracy of Simple Evolving Connectionist System with Varying Distance Formulas

    Science.gov (United States)

    Al-Khowarizmi; Sitompul, O. S.; Suherman; Nababan, E. B.

    2017-12-01

    Simple Evolving Connectionist System (SECoS) is a minimal implementation of Evolving Connectionist Systems (ECoS) in artificial neural networks. The three-layer network architecture of the SECoS could be built based on the given input. In this study, the activation value for the SECoS learning process, which is commonly calculated using normalized Hamming distance, is also calculated using normalized Manhattan distance and normalized Euclidean distance in order to compare the smallest error value and best learning rate obtained. The accuracy of measurement resulted by the three distance formulas are calculated using mean absolute percentage error. In the training phase with several parameters, such as sensitivity threshold, error threshold, first learning rate, and second learning rate, it was found that normalized Euclidean distance is more accurate than both normalized Hamming distance and normalized Manhattan distance. In the case of beta fibrinogen gene -455 G/A polymorphism patients used as training data, the highest mean absolute percentage error value is obtained with normalized Manhattan distance compared to normalized Euclidean distance and normalized Hamming distance. However, the differences are very small that it can be concluded that the three distance formulas used in SECoS do not have a significant effect on the accuracy of the training results.

  15. Whole-genome sequencing of a laboratory-evolved yeast strain

    Directory of Open Access Journals (Sweden)

    Dunham Maitreya J

    2010-02-01

    Full Text Available Abstract Background Experimental evolution of microbial populations provides a unique opportunity to study evolutionary adaptation in response to controlled selective pressures. However, until recently it has been difficult to identify the precise genetic changes underlying adaptation at a genome-wide scale. New DNA sequencing technologies now allow the genome of parental and evolved strains of microorganisms to be rapidly determined. Results We sequenced >93.5% of the genome of a laboratory-evolved strain of the yeast Saccharomyces cerevisiae and its ancestor at >28× depth. Both single nucleotide polymorphisms and copy number amplifications were found, with specific gains over array-based methodologies previously used to analyze these genomes. Applying a segmentation algorithm to quantify structural changes, we determined the approximate genomic boundaries of a 5× gene amplification. These boundaries guided the recovery of breakpoint sequences, which provide insights into the nature of a complex genomic rearrangement. Conclusions This study suggests that whole-genome sequencing can provide a rapid approach to uncover the genetic basis of evolutionary adaptations, with further applications in the study of laboratory selections and mutagenesis screens. In addition, we show how single-end, short read sequencing data can provide detailed information about structural rearrangements, and generate predictions about the genomic features and processes that underlie genome plasticity.

  16. On the relationships between generative encodings, regularity, and learning abilities when evolving plastic artificial neural networks.

    Science.gov (United States)

    Tonelli, Paul; Mouret, Jean-Baptiste

    2013-01-01

    A major goal of bio-inspired artificial intelligence is to design artificial neural networks with abilities that resemble those of animal nervous systems. It is commonly believed that two keys for evolving nature-like artificial neural networks are (1) the developmental process that links genes to nervous systems, which enables the evolution of large, regular neural networks, and (2) synaptic plasticity, which allows neural networks to change during their lifetime. So far, these two topics have been mainly studied separately. The present paper shows that they are actually deeply connected. Using a simple operant conditioning task and a classic evolutionary algorithm, we compare three ways to encode plastic neural networks: a direct encoding, a developmental encoding inspired by computational neuroscience models, and a developmental encoding inspired by morphogen gradients (similar to HyperNEAT). Our results suggest that using a developmental encoding could improve the learning abilities of evolved, plastic neural networks. Complementary experiments reveal that this result is likely the consequence of the bias of developmental encodings towards regular structures: (1) in our experimental setup, encodings that tend to produce more regular networks yield networks with better general learning abilities; (2) whatever the encoding is, networks that are the more regular are statistically those that have the best learning abilities.

  17. It Remains Unknown Whether Filaggrin Gene Mutations Evolved to Increase Cutaneous Synthesis of Vitamin D

    DEFF Research Database (Denmark)

    Thyssen, Jacob P; Elias, Peter M

    2017-01-01

    encountered in Northern Europeans. Importantly, FLG mutation carriers have 10% increased serum vitamin D concentrations compared to controls. Based on these observations, we have proposed that this latitude-dependent gradient of FLG mutations across Europe, Asia and Africa could have provided an evolutionary......About 8-10% of normal Northern Europeans are heterozygous carriers of common FLG mutations, while only 1-4% of southern Europeans display these mutations, and only very rarely are mutations detected in African populations. Although mutations are found in Asians, they are different from those...

  18. Three functionally diverged major White Spot Syndrome Virus structural proteins evolved by gene duplication

    NARCIS (Netherlands)

    Hulten, van M.C.W.; Goldbach, R.W.; Vlak, J.M.

    2000-01-01

    White spot syndrome virus (WSSV) is an invertebrate virus causing considerable mortality in penaeid shrimp. The oval-to-bacilliform shaped virions, isolated from infected Penaeus monodon, contain four major proteins: VP28, VP26, VP24 and VP19 (28, 26, 24 and 19 kDa, respectively). VP26 and VP24 are

  19. The evolution of genes encoding for green fluorescent proteins: insights from cephalochordates (amphioxus)

    Science.gov (United States)

    Yue, Jia-Xing; Holland, Nicholas D.; Holland, Linda Z.; Deheyn, Dimitri D.

    2016-06-01

    Green Fluorescent Protein (GFP) was originally found in cnidarians, and later in copepods and cephalochordates (amphioxus) (Branchiostoma spp). Here, we looked for GFP-encoding genes in Asymmetron, an early-diverged cephalochordate lineage, and found two such genes closely related to some of the Branchiostoma GFPs. Dim fluorescence was found throughout the body in adults of Asymmetron lucayanum, and, as in Branchiostoma floridae, was especially intense in the ripe ovaries. Spectra of the fluorescence were similar between Asymmetron and Branchiostoma. Lineage-specific expansion of GFP-encoding genes in the genus Branchiostoma was observed, largely driven by tandem duplications. Despite such expansion, purifying selection has strongly shaped the evolution of GFP-encoding genes in cephalochordates, with apparent relaxation for highly duplicated clades. All cephalochordate GFP-encoding genes are quite different from those of copepods and cnidarians. Thus, the ancestral cephalochordates probably had GFP, but since GFP appears to be lacking in more early-diverged deuterostomes (echinoderms, hemichordates), it is uncertain whether the ancestral cephalochordates (i.e. the common ancestor of Asymmetron and Branchiostoma) acquired GFP by horizontal gene transfer (HGT) from copepods or cnidarians or inherited it from the common ancestor of copepods and deuterostomes, i.e. the ancestral bilaterians.

  20. Evolution of adaptive phenotypic variation patterns by direct selection for evolvability

    Science.gov (United States)

    Pavlicev, Mihaela; Cheverud, James M.; Wagner, Günter P.

    2011-01-01

    A basic assumption of the Darwinian theory of evolution is that heritable variation arises randomly. In this context, randomness means that mutations arise irrespective of the current adaptive needs imposed by the environment. It is broadly accepted, however, that phenotypic variation is not uniformly distributed among phenotypic traits, some traits tend to covary, while others vary independently, and again others barely vary at all. Furthermore, it is well established that patterns of trait variation differ among species. Specifically, traits that serve different functions tend to be less correlated, as for instance forelimbs and hind limbs in bats and humans, compared with the limbs of quadrupedal mammals. Recently, a novel class of genetic elements has been identified in mouse gene-mapping studies that modify correlations among quantitative traits. These loci are called relationship loci, or relationship Quantitative Trait Loci (rQTL), and affect trait correlations by changing the expression of the existing genetic variation through gene interaction. Here, we present a population genetic model of how natural selection acts on rQTL. Contrary to the usual neo-Darwinian theory, in this model, new heritable phenotypic variation is produced along the selected dimension in response to directional selection. The results predict that selection on rQTL leads to higher correlations among traits that are simultaneously under directional selection. On the other hand, traits that are not simultaneously under directional selection are predicted to evolve lower correlations. These results and the previously demonstrated existence of rQTL variation, show a mechanism by which natural selection can directly enhance the evolvability of complex organisms along lines of adaptive change. PMID:21106581

  1. Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes.

    Science.gov (United States)

    Singh, Param Priya; Arora, Jatin; Isambert, Hervé

    2015-07-01

    Whole genome duplications (WGD) have now been firmly established in all major eukaryotic kingdoms. In particular, all vertebrates descend from two rounds of WGDs, that occurred in their jawless ancestor some 500 MY ago. Paralogs retained from WGD, also coined 'ohnologs' after Susumu Ohno, have been shown to be typically associated with development, signaling and gene regulation. Ohnologs, which amount to about 20 to 35% of genes in the human genome, have also been shown to be prone to dominant deleterious mutations and frequently implicated in cancer and genetic diseases. Hence, identifying ohnologs is central to better understand the evolution of vertebrates and their susceptibility to genetic diseases. Early computational analyses to identify vertebrate ohnologs relied on content-based synteny comparisons between the human genome and a single invertebrate outgroup genome or within the human genome itself. These approaches are thus limited by lineage specific rearrangements in individual genomes. We report, in this study, the identification of vertebrate ohnologs based on the quantitative assessment and integration of synteny conservation between six amniote vertebrates and six invertebrate outgroups. Such a synteny comparison across multiple genomes is shown to enhance the statistical power of ohnolog identification in vertebrates compared to earlier approaches, by overcoming lineage specific genome rearrangements. Ohnolog gene families can be browsed and downloaded for three statistical confidence levels or recompiled for specific, user-defined, significance criteria at http://ohnologs.curie.fr/. In the light of the importance of WGD on the genetic makeup of vertebrates, our analysis provides a useful resource for researchers interested in gaining further insights on vertebrate evolution and genetic diseases.

  2. Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes.

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