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Sample records for duplicate genes

  1. Analysis of Duplicate Genes in Soybean

    Institute of Scientific and Technical Information of China (English)

    C.M. Cai; K.J. Van; M.Y. Kim; S.H. Lee

    2007-01-01

    @@ Gene duplication is a major determinant of the size and gene complement of eukaryotic genomes (Lockton and Gaut, 2005). There are a number of different ways in which duplicate genes can arise (Sankoff, 2001), but the most spectacular method of gene duplication may be whole genome duplication via polyploidization.

  2. Genomic evidence for adaptation by gene duplication.

    Science.gov (United States)

    Qian, Wenfeng; Zhang, Jianzhi

    2014-08-01

    Gene duplication is widely believed to facilitate adaptation, but unambiguous evidence for this hypothesis has been found in only a small number of cases. Although gene duplication may increase the fitness of the involved organisms by doubling gene dosage or neofunctionalization, it may also result in a simple division of ancestral functions into daughter genes, which need not promote adaptation. Hence, the general validity of the adaptation by gene duplication hypothesis remains uncertain. Indeed, a genome-scale experiment found similar fitness effects of deleting pairs of duplicate genes and deleting individual singleton genes from the yeast genome, leading to the conclusion that duplication rarely results in adaptation. Here we contend that the above comparison is unfair because of a known duplication bias among genes with different fitness contributions. To rectify this problem, we compare homologous genes from the budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe. We discover that simultaneously deleting a duplicate gene pair in S. cerevisiae reduces fitness significantly more than deleting their singleton counterpart in S. pombe, revealing post-duplication adaptation. The duplicates-singleton difference in fitness effect is not attributable to a potential increase in gene dose after duplication, suggesting that the adaptation is owing to neofunctionalization, which we find to be explicable by acquisitions of binary protein-protein interactions rather than gene expression changes. These results provide genomic evidence for the role of gene duplication in organismal adaptation and are important for understanding the genetic mechanisms of evolutionary innovation.

  3. Duplicability of self-interacting human genes.

    LENUS (Irish Health Repository)

    Pérez-Bercoff, Asa

    2010-01-01

    BACKGROUND: There is increasing interest in the evolution of protein-protein interactions because this should ultimately be informative of the patterns of evolution of new protein functions within the cell. One model proposes that the evolution of new protein-protein interactions and protein complexes proceeds through the duplication of self-interacting genes. This model is supported by data from yeast. We examined the relationship between gene duplication and self-interaction in the human genome. RESULTS: We investigated the patterns of self-interaction and duplication among 34808 interactions encoded by 8881 human genes, and show that self-interacting proteins are encoded by genes with higher duplicability than genes whose proteins lack this type of interaction. We show that this result is robust against the system used to define duplicate genes. Finally we compared the presence of self-interactions amongst proteins whose genes have duplicated either through whole-genome duplication (WGD) or small-scale duplication (SSD), and show that the former tend to have more interactions in general. After controlling for age differences between the two sets of duplicates this result can be explained by the time since the gene duplication. CONCLUSIONS: Genes encoding self-interacting proteins tend to have higher duplicability than proteins lacking self-interactions. Moreover these duplicate genes have more often arisen through whole-genome rather than small-scale duplication. Finally, self-interacting WGD genes tend to have more interaction partners in general in the PIN, which can be explained by their overall greater age. This work adds to our growing knowledge of the importance of contextual factors in gene duplicability.

  4. Special Issue: Gene Conversion in Duplicated Genes

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    Hideki Innan

    2011-06-01

    Full Text Available Gene conversion is an outcome of recombination, causing non-reciprocal transfer of a DNA fragment. Several decades later than the discovery of crossing over, gene conversion was first recognized in fungi when non-Mendelian allelic distortion was observed. Gene conversion occurs when a double-strand break is repaired by using homologous sequences in the genome. In meiosis, there is a strong preference to use the orthologous region (allelic gene conversion, which causes non-Mendelian allelic distortion, but paralogous or duplicated regions can also be used for the repair (inter-locus gene conversion, also referred to as non-allelic and ectopic gene conversion. The focus of this special issue is the latter, interlocus gene conversion; the rate is lower than allelic gene conversion but it has more impact on phenotype because more drastic changes in DNA sequence are involved.

  5. Yeast genome duplication was followed by asynchronous differentiation of duplicated genes

    DEFF Research Database (Denmark)

    Langkjær, Rikke Breinhold; Cliften, P.F.; Johnston, M.

    2003-01-01

    Gene redundancy has been observed in yeast, plant and human genomes, and is thought to be a consequence of whole-genome duplications(1-3). Baker's yeast, Saccharomyces cerevisiae, contains several hundred duplicated genes(1). Duplication(s) could have occurred before or after a given speciation. ...

  6. Effect of Duplicate Genes on Mouse Genetic Robustness: An Update

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    Zhixi Su

    2014-01-01

    Full Text Available In contrast to S. cerevisiae and C. elegans, analyses based on the current knockout (KO mouse phenotypes led to the conclusion that duplicate genes had almost no role in mouse genetic robustness. It has been suggested that the bias of mouse KO database toward ancient duplicates may possibly cause this knockout duplicate puzzle, that is, a very similar proportion of essential genes (PE between duplicate genes and singletons. In this paper, we conducted an extensive and careful analysis for the mouse KO phenotype data and corroborated a strong effect of duplicate genes on mouse genetics robustness. Moreover, the effect of duplicate genes on mouse genetic robustness is duplication-age dependent, which holds after ruling out the potential confounding effect from coding-sequence conservation, protein-protein connectivity, functional bias, or the bias of duplicates generated by whole genome duplication (WGD. Our findings suggest that two factors, the sampling bias toward ancient duplicates and very ancient duplicates with a proportion of essential genes higher than that of singletons, have caused the mouse knockout duplicate puzzle; meanwhile, the effect of genetic buffering may be correlated with sequence conservation as well as protein-protein interactivity.

  7. Gene duplication as a major force in evolution

    Indian Academy of Sciences (India)

    Santoshkumar Magadum; Urbi Banerjee; Priyadharshini Murugan; Doddabhimappa Gangapur; Rajasekar Ravikesavan

    2013-04-01

    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 unequal crossing over, retroposition or chromosomal (or genome) duplication. Understanding the mechanisms that generate duplicate gene copies and the subsequent dynamics among gene duplicates is vital because these investigations shed light on localized and genomewide aspects of evolutionary forces shaping intra-specific and inter-specific genome contents, evolutionary relationships, and interactions. Based on whole-genome analysis of Arabidopsis thaliana, there is compelling evidence that angiosperms underwent two whole-genome duplication events early during their evolutionary history. Recent studies have shown that these events were crucial for creation of many important developmental and regulatory genes found in extant angiosperm genomes. Recent studies also provide strong indications that even yeast (Saccharomyces cerevisiae), with its compact genome, is in fact an ancient tetraploid. Gene duplication can provide new genetic material for mutation, drift and selection to act upon, the result of which is specialized or new gene functions. Without gene duplication the plasticity of a genome or species in adapting to changing environments would be severely limited. Whether a duplicate is retained depends upon its function, its mode of duplication, (i.e. whether it was duplicated during a whole-genome duplication event), the species in which it occurs, and its expression rate. The exaptation of preexisting secondary functions is an important feature in gene evolution, just as it is in morphological evolution.

  8. Molecular trajectories leading to the alternative fates of duplicate genes.

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    Michael Marotta

    Full Text Available Gene duplication generates extra gene copies in which mutations can accumulate without risking the function of pre-existing genes. Such mutations modify duplicates and contribute to evolutionary novelties. However, the vast majority of duplicates appear to be short-lived and experience duplicate silencing within a few million years. Little is known about the molecular mechanisms leading to these alternative fates. Here we delineate differing molecular trajectories of a relatively recent duplication event between humans and chimpanzees by investigating molecular properties of a single duplicate: DNA sequences, gene expression and promoter activities. The inverted duplication of the Glutathione S-transferase Theta 2 (GSTT2 gene had occurred at least 7 million years ago in the common ancestor of African great apes and is preserved in chimpanzees (Pan troglodytes, whereas a deletion polymorphism is prevalent in humans. The alternative fates are associated with expression divergence between these species, and reduced expression in humans is regulated by silencing mutations that have been propagated between duplicates by gene conversion. In contrast, selective constraint preserved duplicate divergence in chimpanzees. The difference in evolutionary processes left a unique DNA footprint in which dying duplicates are significantly more similar to each other (99.4% than preserved ones. Such molecular trajectories could provide insights for the mechanisms underlying duplicate life and death in extant genomes.

  9. Benchmarking Transcriptome Quantification Methods for Duplicated Genes in Xenopus laevis.

    Science.gov (United States)

    Kwon, Taejoon

    2015-01-01

    Xenopus is an important model organism for the study of genome duplication in vertebrates. With the full genome sequence of diploid Xenopus tropicalis available, and that of allotetraploid X. laevis close to being finished, we will be able to expand our understanding of how duplicated genes have evolved. One of the key features in the study of the functional consequence of gene duplication is how their expression patterns vary across different conditions, and RNA-seq seems to have enough resolution to discriminate the expression of highly similar duplicated genes. However, most of the current RNA-seq analysis methods were not designed to study samples with duplicate genes such as in X. laevis. Here, various computational methods to quantify gene expression in RNA-seq data were evaluated, using 2 independent X. laevis egg RNA-seq datasets and 2 reference databases for duplicated genes. The fact that RNA-seq can measure expression levels of similar duplicated genes was confirmed, but long paired-end reads are more informative than short single-end reads to discriminate duplicated genes. Also, it was found that bowtie, one of the most popular mappers in RNA-seq analysis, reports significantly smaller numbers of unique hits according to a mapping quality score compared to other mappers tested (BWA, GSNAP, STAR). Calculated from unique hits based on a mapping quality score, both expression levels and the expression ratio of duplicated genes can be estimated consistently among biological replicates, demonstrating that this method can successfully discriminate the expression of each copy of a duplicated gene pair. This comprehensive evaluation will be a useful guideline for studying gene expression of organisms with genome duplication using RNA-seq in the future.

  10. Inferring angiosperm phylogeny from EST data with widespread gene duplication

    OpenAIRE

    Sanderson, Michael J.; McMahon, Michelle M.

    2007-01-01

    Background Most studies inferring species phylogenies use sequences from single copy genes or sets of orthologs culled from gene families. For taxa such as plants, with very high levels of gene duplication in their nuclear genomes, this has limited the exploitation of nuclear sequences for phylogenetic studies, such as those available in large EST libraries. One rarely used method of inference, gene tree parsimony, can infer species trees from gene families undergoing duplication and loss, bu...

  11. Gene duplication models for directed networks with limits on growth

    Science.gov (United States)

    Enemark, Jakob; Sneppen, Kim

    2007-11-01

    Background: Duplication of genes is important for evolution of molecular networks. Many authors have therefore considered gene duplication as a driving force in shaping the topology of molecular networks. In particular it has been noted that growth via duplication would act as an implicit means of preferential attachment, and thereby provide the observed broad degree distributions of molecular networks. Results: We extend current models of gene duplication and rewiring by including directions and the fact that molecular networks are not a result of unidirectional growth. We introduce upstream sites and downstream shapes to quantify potential links during duplication and rewiring. We find that this in itself generates the observed scaling of transcription factors for genome sites in prokaryotes. The dynamical model can generate a scale-free degree distribution, p(k)\\propto 1/k^{\\gamma } , with exponent γ = 1 in the non-growing case, and with γ>1 when the network is growing. Conclusions: We find that duplication of genes followed by substantial recombination of upstream regions could generate features of genetic regulatory networks. Our steady state degree distribution is however too broad to be consistent with data, thereby suggesting that selective pruning acts as a main additional constraint on duplicated genes. Our analysis shows that gene duplication can only be a main cause for the observed broad degree distributions if there are also substantial recombinations between upstream regions of genes.

  12. Histone modification pattern evolution after yeast gene duplication

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    Zou Yangyun

    2012-07-01

    Full Text Available Abstract Background Gene duplication and subsequent functional divergence especially expression divergence have been widely considered as main sources for evolutionary innovations. Many studies evidenced that genetic regulatory network evolved rapidly shortly after gene duplication, thus leading to accelerated expression divergence and diversification. However, little is known whether epigenetic factors have mediated the evolution of expression regulation since gene duplication. In this study, we conducted detailed analyses on yeast histone modification (HM, the major epigenetics type in this organism, as well as other available functional genomics data to address this issue. Results Duplicate genes, on average, share more common HM-code patterns than random singleton pairs in their promoters and open reading frames (ORF. Though HM-code divergence between duplicates in both promoter and ORF regions increase with their sequence divergence, the HM-code in ORF region evolves slower than that in promoter region, probably owing to the functional constraints imposed on protein sequences. After excluding the confounding effect of sequence divergence (or evolutionary time, we found the evidence supporting the notion that in yeast, the HM-code may co-evolve with cis- and trans-regulatory factors. Moreover, we observed that deletion of some yeast HM-related enzymes increases the expression divergence between duplicate genes, yet the effect is lower than the case of transcription factor (TF deletion or environmental stresses. Conclusions Our analyses demonstrate that after gene duplication, yeast histone modification profile between duplicates diverged with evolutionary time, similar to genetic regulatory elements. Moreover, we found the evidence of the co-evolution between genetic and epigenetic elements since gene duplication, together contributing to the expression divergence between duplicate genes.

  13. Gene and genome duplication in Acanthamoeba polyphaga Mimivirus.

    Science.gov (United States)

    Suhre, Karsten

    2005-11-01

    Gene duplication is key to molecular evolution in all three domains of life and may be the first step in the emergence of new gene function. It is a well-recognized feature in large DNA viruses but has not been studied extensively in the largest known virus to date, the recently discovered Acanthamoeba polyphaga Mimivirus. Here, I present a systematic analysis of gene and genome duplication events in the mimivirus genome. I found that one-third of the mimivirus genes are related to at least one other gene in the mimivirus genome, either through a large segmental genome duplication event that occurred in the more remote past or through more recent gene duplication events, which often occur in tandem. This shows that gene and genome duplication played a major role in shaping the mimivirus genome. Using multiple alignments, together with remote-homology detection methods based on Hidden Markov Model comparison, I assign putative functions to some of the paralogous gene families. I suggest that a large part of the duplicated mimivirus gene families are likely to interfere with important host cell processes, such as transcription control, protein degradation, and cell regulatory processes. My findings support the view that large DNA viruses are complex evolving organisms, possibly deeply rooted within the tree of life, and oppose the paradigm that viral evolution is dominated by lateral gene acquisition, at least in regard to large DNA viruses.

  14. Duplication and maintenance of the Myb genes of vertebrate animals

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    Colin J. Davidson

    2012-11-01

    Gene duplication is an important means of generating new genes. The major mechanisms by which duplicated genes are preserved in the face of purifying selection are thought to be neofunctionalization, subfunctionalization, and increased gene dosage. However, very few duplicated gene families in vertebrate species have been analyzed by functional tests in vivo. We have therefore examined the three vertebrate Myb genes (c-Myb, A-Myb, and B-Myb by cytogenetic map analysis, by sequence analysis, and by ectopic expression in Drosophila. We provide evidence that the vertebrate Myb genes arose by two rounds of regional genomic duplication. We found that ubiquitous expression of c-Myb and A-Myb, but not of B-Myb or Drosophila Myb, was lethal in Drosophila. Expression of any of these genes during early larval eye development was well tolerated. However, expression of c-Myb and A-Myb, but not of B-Myb or Drosophila Myb, during late larval eye development caused drastic alterations in adult eye morphology. Mosaic analysis implied that this eye phenotype was cell-autonomous. Interestingly, some of the eye phenotypes caused by the retroviral v-Myb oncogene and the normal c-Myb proto-oncogene from which v-Myb arose were quite distinct. Finally, we found that post-translational modifications of c-Myb by the GSK-3 protein kinase and by the Ubc9 SUMO-conjugating enzyme that normally occur in vertebrate cells can modify the eye phenotype caused by c-Myb in Drosophila. These results support a model in which the three Myb genes of vertebrates arose by two sequential duplications. The first duplication was followed by a subfunctionalization of gene expression, then neofunctionalization of protein function to yield a c/A-Myb progenitor. The duplication of this progenitor was followed by subfunctionalization of gene expression to give rise to tissue-specific c-Myb and A-Myb genes.

  15. Gene duplication in the genome of parasitic Giardia lamblia

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    Flores Roberto

    2010-02-01

    Full Text Available Abstract Background Giardia are a group of widespread intestinal protozoan parasites in a number of vertebrates. Much evidence from G. lamblia indicated they might be the most primitive extant eukaryotes. When and how such a group of the earliest branching unicellular eukaryotes developed the ability to successfully parasitize the latest branching higher eukaryotes (vertebrates is an intriguing question. Gene duplication has long been thought to be the most common mechanism in the production of primary resources for the origin of evolutionary novelties. In order to parse the evolutionary trajectory of Giardia parasitic lifestyle, here we carried out a genome-wide analysis about gene duplication patterns in G. lamblia. Results Although genomic comparison showed that in G. lamblia the contents of many fundamental biologic pathways are simplified and the whole genome is very compact, in our study 40% of its genes were identified as duplicated genes. Evolutionary distance analyses of these duplicated genes indicated two rounds of large scale duplication events had occurred in G. lamblia genome. Functional annotation of them further showed that the majority of recent duplicated genes are VSPs (Variant-specific Surface Proteins, which are essential for the successful parasitic life of Giardia in hosts. Based on evolutionary comparison with their hosts, it was found that the rapid expansion of VSPs in G. lamblia is consistent with the evolutionary radiation of placental mammals. Conclusions Based on the genome-wide analysis of duplicated genes in G. lamblia, we found that gene duplication was essential for the origin and evolution of Giardia parasitic lifestyle. The recent expansion of VSPs uniquely occurring in G. lamblia is consistent with the increment of its hosts. Therefore we proposed a hypothesis that the increment of Giradia hosts might be the driving force for the rapid expansion of VSPs.

  16. Complexity of Gene Expression Evolution after Duplication: Protein Dosage Rebalancing

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    Igor B. Rogozin

    2014-01-01

    Full Text Available Ongoing debates about functional importance of gene duplications have been recently intensified by a heated discussion of the “ortholog conjecture” (OC. Under the OC, which is central to functional annotation of genomes, orthologous genes are functionally more similar than paralogous genes at the same level of sequence divergence. However, a recent study challenged the OC by reporting a greater functional similarity, in terms of gene ontology (GO annotations and expression profiles, among within-species paralogs compared to orthologs. These findings were taken to indicate that functional similarity of homologous genes is primarily determined by the cellular context of the genes, rather than evolutionary history. Subsequent studies suggested that the OC appears to be generally valid when applied to mammalian evolution but the complete picture of evolution of gene expression also has to incorporate lineage-specific aspects of paralogy. The observed complexity of gene expression evolution after duplication can be explained through selection for gene dosage effect combined with the duplication-degeneration-complementation model. This paper discusses expression divergence of recent duplications occurring before functional divergence of proteins encoded by duplicate genes.

  17. Simultaneous identification of duplications and lateral gene transfers.

    Science.gov (United States)

    Tofigh, Ali; Hallett, Michael; Lagergren, Jens

    2011-01-01

    The incongruency between a gene tree and a corresponding species tree can be attributed to evolutionary events such as gene duplication and gene loss. This paper describes a combinatorial model where so-called DTL-scenarios are used to explain the differences between a gene tree and a corresponding species tree taking into account gene duplications, gene losses, and lateral gene transfers (also known as horizontal gene transfers). The reasonable biological constraint that a lateral gene transfer may only occur between contemporary species leads to the notion of acyclic DTL-scenarios. Parsimony methods are introduced by defining appropriate optimization problems. We show that finding most parsimonious acyclic DTL-scenarios is NP-hard. However, by dropping the condition of acyclicity, the problem becomes tractable, and we provide a dynamic programming algorithm as well as a fixed-parameter tractable algorithm for finding most parsimonious DTL-scenarios.

  18. Exon duplications in the ATP7A gene

    DEFF Research Database (Denmark)

    Mogensen, Mie; Skjørringe, Tina; Kodama, Hiroko

    2011-01-01

    BACKGROUND: Menkes disease (MD) is an X-linked, fatal neurodegenerative disorder of copper metabolism, caused by mutations in the ATP7A gene. Thirty-three Menkes patients in whom no mutation had been detected with standard diagnostic tools were screened for exon duplications in the ATP7A gene...

  19. FUNCTIONAL SPECIALIZATION OF DUPLICATED FLAVONOID BIOSYNTHESIS GENES IN WHEAT

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    Khlestkina E.

    2012-08-01

    Full Text Available Gene duplication followed by subfunctionalization and neofunctionalization is of a great evolutionary importance. In plant genomes, duplicated genes may result from either polyploidization (homoeologous genes or segmental chromosome duplications (paralogous genes. In allohexaploid wheat Triticum aestivum L. (2n=6x=42, genome BBAADD, both homoeologous and paralogous copies were found for the regulatory gene Myc encoding MYC-like transcriptional factor in the biosynthesis of flavonoid pigments, anthocyanins, and for the structural gene F3h encoding one of the key enzymes of flavonoid biosynthesis, flavanone 3-hydroxylase. From the 5 copies (3 homoeologous and 2 paralogous of the Myc gene found in T. aestivum, only one plays a regulatory role in anthocyanin biosynthesis, interacting complementary with another transcriptional factor (MYB-like to confer purple pigmentation of grain pericarp in wheat. The role and functionality of the other 4 copies of the Myc gene remain unknown. From the 4 functional copies of the F3h gene in T. aestivum, three homoeologues have similar function. They are expressed in wheat organs colored with anthocyanins or in the endosperm, participating there in biosynthesis of uncolored flavonoid substances. The fourth copy (the B-genomic paralogue is transcribed neither in wheat organs colored with anthocyanins nor in seeds, however, it’s expression has been noticed in roots of aluminium-stressed plants, where the three homoeologous copies are not active. Functional diversification of the duplicated flavonoid biosynthesis genes in wheat may be a reason for maintenance of the duplicated copies and preventing them from pseudogenization.The study was supported by RFBR (11-04-92707. We also thank Ms. Galina Generalova for technical assistance.

  20. Prevalent role of gene features in determining evolutionary fates of whole-genome duplication duplicated genes in flowering plants.

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    Jiang, Wen-kai; Liu, Yun-long; Xia, En-hua; Gao, Li-zhi

    2013-04-01

    The evolution of genes and genomes after polyploidization has been the subject of extensive studies in evolutionary biology and plant sciences. While a significant number of duplicated genes are rapidly removed during a process called fractionation, which operates after the whole-genome duplication (WGD), another considerable number of genes are retained preferentially, leading to the phenomenon of biased gene retention. However, the evolutionary mechanisms underlying gene retention after WGD remain largely unknown. Through genome-wide analyses of sequence and functional data, we comprehensively investigated the relationships between gene features and the retention probability of duplicated genes after WGDs in six plant genomes, Arabidopsis (Arabidopsis thaliana), poplar (Populus trichocarpa), soybean (Glycine max), rice (Oryza sativa), sorghum (Sorghum bicolor), and maize (Zea mays). The results showed that multiple gene features were correlated with the probability of gene retention. Using a logistic regression model based on principal component analysis, we resolved evolutionary rate, structural complexity, and GC3 content as the three major contributors to gene retention. Cluster analysis of these features further classified retained genes into three distinct groups in terms of gene features and evolutionary behaviors. Type I genes are more prone to be selected by dosage balance; type II genes are possibly subject to subfunctionalization; and type III genes may serve as potential targets for neofunctionalization. This study highlights that gene features are able to act jointly as primary forces when determining the retention and evolution of WGD-derived duplicated genes in flowering plants. These findings thus may help to provide a resolution to the debate on different evolutionary models of gene fates after WGDs.

  1. Inferring angiosperm phylogeny from EST data with widespread gene duplication.

    Science.gov (United States)

    Sanderson, Michael J; McMahon, Michelle M

    2007-02-08

    Most studies inferring species phylogenies use sequences from single copy genes or sets of orthologs culled from gene families. For taxa such as plants, with very high levels of gene duplication in their nuclear genomes, this has limited the exploitation of nuclear sequences for phylogenetic studies, such as those available in large EST libraries. One rarely used method of inference, gene tree parsimony, can infer species trees from gene families undergoing duplication and loss, but its performance has not been evaluated at a phylogenomic scale for EST data in plants. A gene tree parsimony analysis based on EST data was undertaken for six angiosperm model species and Pinus, an outgroup. Although a large fraction of the tentative consensus sequences obtained from the TIGR database of ESTs was assembled into homologous clusters too small to be phylogenetically informative, some 557 clusters contained promising levels of information. Based on maximum likelihood estimates of the gene trees obtained from these clusters, gene tree parsimony correctly inferred the accepted species tree with strong statistical support. A slight variant of this species tree was obtained when maximum parsimony was used to infer the individual gene trees instead. Despite the complexity of the EST data and the relatively small fraction eventually used in inferring a species tree, the gene tree parsimony method performed well in the face of very high apparent rates of duplication.

  2. Concerted evolution of duplicated protein-coding genes in Drosophila.

    OpenAIRE

    Hickey, D. A.; Bally-Cuif, L.; Abukashawa, S; Payant, V; Benkel, B F

    1991-01-01

    Very rapid rates of gene conversion were observed between duplicated alpha-amylase-coding sequences in Drosophila melanogaster. This gene conversion process was also seen in the related species Drosophila erecta. Specifically, there is virtual sequence identity between the coding regions of the two genes within each species, while the sequence divergence between species is close to that expected based on their phylogenetic relationship. The flanking, noncoding regions are much more highly div...

  3. Concerted evolution of duplicated protein-coding genes in Drosophila.

    Science.gov (United States)

    Hickey, D A; Bally-Cuif, L; Abukashawa, S; Payant, V; Benkel, B F

    1991-03-01

    Very rapid rates of gene conversion were observed between duplicated alpha-amylase-coding sequences in Drosophila melanogaster. This gene conversion process was also seen in the related species Drosophila erecta. Specifically, there is virtual sequence identity between the coding regions of the two genes within each species, while the sequence divergence between species is close to that expected based on their phylogenetic relationship. The flanking, noncoding regions are much more highly diverged and do not appear to be subject to gene conversion. Comparison of amylase sequences between the two species provides a clear demonstration that recurrent gene conversion does indeed lead to the concerted evolution of the gene pair.

  4. Familial Lymphoproliferative Malignancies and Tandem Duplication of NF1 Gene

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    Gustavo Fernandes

    2014-01-01

    Full Text Available Background. Neurofibromatosis type 1 is a genetic disorder caused by loss-of-function mutations in a tumor suppressor gene (NF1 which codifies the protein neurofibromin. The frequent genetic alterations that modify neurofibromin function are deletions and insertions. Duplications are rare and phenotype in patients bearing duplication of NF1 gene is thought to be restricted to developmental abnormalities, with no reference to cancer susceptibility in these patients. We evaluated a patient who presented with few clinical signs of neurofibromatosis type 1 and a conspicuous personal and familiar history of different types of cancer, especially lymphoproliferative malignancies. The coding region of the NF-1 gene was analyzed by real-time polymerase chain reaction and direct sequencing. Multiplex ligation-dependent probe amplification was performed to detect the number of mutant copies. The NF1 gene analysis showed the following alterations: mosaic duplication of NF1, TRAF4, and MYO1D. Fluorescence in situ hybridization using probes (RP5-1002G3 and RP5-92689 flanking NF1 gene in 17q11.2 and CEP17 for 17q11.11.1 was performed. There were three signals (RP5-1002G3conRP5-92689 in the interphases analyzed and two signals (RP5-1002G3conRP5-92689 in 93% of cells. These findings show a tandem duplication of 17q11.2. Conclusion. The case suggests the possibility that NF1 gene duplication may be associated with a phenotype characterized by lymphoproliferative disorders.

  5. A role for gene duplication and natural variation of gene expression in the evolution of metabolism.

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    Daniel J Kliebenstein

    Full Text Available BACKGROUND: Most eukaryotic genomes have undergone whole genome duplications during their evolutionary history. Recent studies have shown that the function of these duplicated genes can diverge from the ancestral gene via neo- or sub-functionalization within single genotypes. An additional possibility is that gene duplicates may also undergo partitioning of function among different genotypes of a species leading to genetic differentiation. Finally, the ability of gene duplicates to diverge may be limited by their biological function. METHODOLOGY/PRINCIPAL FINDINGS: To test these hypotheses, I estimated the impact of gene duplication and metabolic function upon intraspecific gene expression variation of segmental and tandem duplicated genes within Arabidopsis thaliana. In all instances, the younger tandem duplicated genes showed higher intraspecific gene expression variation than the average Arabidopsis gene. Surprisingly, the older segmental duplicates also showed evidence of elevated intraspecific gene expression variation albeit typically lower than for the tandem duplicates. The specific biological function of the gene as defined by metabolic pathway also modulated the level of intraspecific gene expression variation. The major energy metabolism and biosynthetic pathways showed decreased variation, suggesting that they are constrained in their ability to accumulate gene expression variation. In contrast, a major herbivory defense pathway showed significantly elevated intraspecific variation suggesting that it may be under pressure to maintain and/or generate diversity in response to fluctuating insect herbivory pressures. CONCLUSION: These data show that intraspecific variation in gene expression is facilitated by an interaction of gene duplication and biological activity. Further, this plays a role in controlling diversity of plant metabolism.

  6. Recombination facilitates neofunctionalization of duplicate genes via originalization

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    Huang Ren

    2010-06-01

    Full Text Available Abstract Background Recently originalization was proposed to be an effective way of duplicate-gene preservation, in which recombination provokes the high frequency of original (or wild-type allele on both duplicated loci. Because the high frequency of wild-type allele might drive the arising and accumulating of advantageous mutation, it is hypothesized that recombination might enlarge the probability of neofunctionalization (Pneo of duplicate genes. In this article this hypothesis has been tested theoretically. Results Results show that through originalization recombination might not only shorten mean time to neofunctionalizaiton, but also enlarge Pneo. Conclusions Therefore, recombination might facilitate neofunctionalization via originalization. Several extensive applications of these results on genomic evolution have been discussed: 1. Time to nonfunctionalization can be much longer than a few million generations expected before; 2. Homogenization on duplicated loci results from not only gene conversion, but also originalization; 3. Although the rate of advantageous mutation is much small compared with that of degenerative mutation, Pneo cannot be expected to be small.

  7. The Phenotypic Plasticity of Duplicated Genes in Saccharomyces cerevisiae and the Origin of Adaptations

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    Florian Mattenberger

    2017-01-01

    Full Text Available Gene and genome duplication are the major sources of biological innovations in plants and animals. Functional and transcriptional divergence between the copies after gene duplication has been considered the main driver of innovations . However, here we show that increased phenotypic plasticity after duplication plays a more major role than thought before in the origin of adaptations. We perform an exhaustive analysis of the transcriptional alterations of duplicated genes in the unicellular eukaryote Saccharomyces cerevisiae when challenged with five different environmental stresses. Analysis of the transcriptomes of yeast shows that gene duplication increases the transcriptional response to environmental changes, with duplicated genes exhibiting signatures of adaptive transcriptional patterns in response to stress. The mechanism of duplication matters, with whole-genome duplicates being more transcriptionally altered than small-scale duplicates. The predominant transcriptional pattern follows the classic theory of evolution by gene duplication; with one gene copy remaining unaltered under stress, while its sister copy presents large transcriptional plasticity and a prominent role in adaptation. Moreover, we find additional transcriptional profiles that are suggestive of neo- and subfunctionalization of duplicate gene copies. These patterns are strongly correlated with the functional dependencies and sequence divergence profiles of gene copies. We show that, unlike singletons, duplicates respond more specifically to stress, supporting the role of natural selection in the transcriptional plasticity of duplicates. Our results reveal the underlying transcriptional complexity of duplicated genes and its role in the origin of adaptations.

  8. Signals of historical interlocus gene conversion in human segmental duplications.

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    Beth L Dumont

    Full Text Available Standard methods of DNA sequence analysis assume that sequences evolve independently, yet this assumption may not be appropriate for segmental duplications that exchange variants via interlocus gene conversion (IGC. Here, we use high quality multiple sequence alignments from well-annotated segmental duplications to systematically identify IGC signals in the human reference genome. Our analysis combines two complementary methods: (i a paralog quartet method that uses DNA sequence simulations to identify a statistical excess of sites consistent with inter-paralog exchange, and (ii the alignment-based method implemented in the GENECONV program. One-quarter (25.4% of the paralog families in our analysis harbor clear IGC signals by the quartet approach. Using GENECONV, we identify 1477 gene conversion tracks that cumulatively span 1.54 Mb of the genome. Our analyses confirm the previously reported high rates of IGC in subtelomeric regions and Y-chromosome palindromes, and identify multiple novel IGC hotspots, including the pregnancy specific glycoproteins and the neuroblastoma breakpoint gene families. Although the duplication history of a paralog family is described by a single tree, we show that IGC has introduced incredible site-to-site variation in the evolutionary relationships among paralogs in the human genome. Our findings indicate that IGC has left significant footprints in patterns of sequence diversity across segmental duplications in the human genome, out-pacing the contributions of single base mutation by orders of magnitude. Collectively, the IGC signals we report comprise a catalog that will provide a critical reference for interpreting observed patterns of DNA sequence variation across duplicated genomic regions, including targets of recent adaptive evolution in humans.

  9. Evolution of the duplicated intracellular lipid-binding protein genes of teleost fishes.

    Science.gov (United States)

    Venkatachalam, Ananda B; Parmar, Manoj B; Wright, Jonathan M

    2017-08-01

    Increasing organismal complexity during the evolution of life has been attributed to the duplication of genes and entire genomes. More recently, theoretical models have been proposed that postulate the fate of duplicated genes, among them the duplication-degeneration-complementation (DDC) model. In the DDC model, the common fate of a duplicated gene is lost from the genome owing to nonfunctionalization. Duplicated genes are retained in the genome either by subfunctionalization, where the functions of the ancestral gene are sub-divided between the sister duplicate genes, or by neofunctionalization, where one of the duplicate genes acquires a new function. Both processes occur either by loss or gain of regulatory elements in the promoters of duplicated genes. Here, we review the genomic organization, evolution, and transcriptional regulation of the multigene family of intracellular lipid-binding protein (iLBP) genes from teleost fishes. Teleost fishes possess many copies of iLBP genes owing to a whole genome duplication (WGD) early in the teleost fish radiation. Moreover, the retention of duplicated iLBP genes is substantially higher than the retention of all other genes duplicated in the teleost genome. The fatty acid-binding protein genes, a subfamily of the iLBP multigene family in zebrafish, are differentially regulated by peroxisome proliferator-activated receptor (PPAR) isoforms, which may account for the retention of iLBP genes in the zebrafish genome by the process of subfunctionalization of cis-acting regulatory elements in iLBP gene promoters.

  10. Hox gene duplications correlate with posterior heteronomy in scorpions.

    Science.gov (United States)

    Sharma, Prashant P; Schwager, Evelyn E; Extavour, Cassandra G; Wheeler, Ward C

    2014-10-07

    The evolutionary success of the largest animal phylum, Arthropoda, has been attributed to tagmatization, the coordinated evolution of adjacent metameres to form morphologically and functionally distinct segmental regions called tagmata. Specification of regional identity is regulated by the Hox genes, of which 10 are inferred to be present in the ancestor of arthropods. With six different posterior segmental identities divided into two tagmata, the bauplan of scorpions is the most heteronomous within Chelicerata. Expression domains of the anterior eight Hox genes are conserved in previously surveyed chelicerates, but it is unknown how Hox genes regionalize the three tagmata of scorpions. Here, we show that the scorpion Centruroides sculpturatus has two paralogues of all Hox genes except Hox3, suggesting cluster and/or whole genome duplication in this arachnid order. Embryonic anterior expression domain boundaries of each of the last four pairs of Hox genes (two paralogues each of Antp, Ubx, abd-A and Abd-B) are unique and distinguish segmental groups, such as pectines, book lungs and the characteristic tail, while maintaining spatial collinearity. These distinct expression domains suggest neofunctionalization of Hox gene paralogues subsequent to duplication. Our data reconcile previous understanding of Hox gene function across arthropods with the extreme heteronomy of scorpions.

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

    Directory of Open Access Journals (Sweden)

    Lu Jianguo

    2012-06-01

    Full Text Available Abstract Background 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. Results 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. Conclusions 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

  12. A salmonid EST genomic study: genes, duplications, phylogeny and microarrays

    Directory of Open Access Journals (Sweden)

    Brahmbhatt Sonal

    2008-11-01

    Full Text Available Abstract Background Salmonids are of interest because of their relatively recent genome duplication, and their extensive use in wild fisheries and aquaculture. A comprehensive gene list and a comparison of genes in some of the different species provide valuable genomic information for one of the most widely studied groups of fish. Results 298,304 expressed sequence tags (ESTs from Atlantic salmon (69% of the total, 11,664 chinook, 10,813 sockeye, 10,051 brook trout, 10,975 grayling, 8,630 lake whitefish, and 3,624 northern pike ESTs were obtained in this study and have been deposited into the public databases. Contigs were built and putative full-length Atlantic salmon clones have been identified. A database containing ESTs, assemblies, consensus sequences, open reading frames, gene predictions and putative annotation is available. The overall similarity between Atlantic salmon ESTs and those of rainbow trout, chinook, sockeye, brook trout, grayling, lake whitefish, northern pike and rainbow smelt is 93.4, 94.2, 94.6, 94.4, 92.5, 91.7, 89.6, and 86.2% respectively. An analysis of 78 transcript sets show Salmo as a sister group to Oncorhynchus and Salvelinus within Salmoninae, and Thymallinae as a sister group to Salmoninae and Coregoninae within Salmonidae. Extensive gene duplication is consistent with a genome duplication in the common ancestor of salmonids. Using all of the available EST data, a new expanded salmonid cDNA microarray of 32,000 features was created. Cross-species hybridizations to this cDNA microarray indicate that this resource will be useful for studies of all 68 salmonid species. Conclusion An extensive collection and analysis of salmonid RNA putative transcripts indicate that Pacific salmon, Atlantic salmon and charr are 94–96% similar while the more distant whitefish, grayling, pike and smelt are 93, 92, 89 and 86% similar to salmon. The salmonid transcriptome reveals a complex history of gene duplication that is

  13. Matrix Gla protein and osteocalcin: from gene duplication to neofunctionalization.

    Science.gov (United States)

    Cancela, M Leonor; Laizé, Vincent; Conceição, Natércia

    2014-11-01

    Osteocalcin (OC or bone Gla protein, BGP) and matrix Gla protein (MGP) are two members of the growing family of vitamin K-dependent (VKD) proteins. They were the first VKD proteins found not to be involved in coagulation and synthesized outside the liver. Both proteins were isolated from bone although it is now known that only OC is synthesized by bone cells under normal physiological conditions, but since both proteins can bind calcium and hydroxyapatite, they can also accumulate in bone. Both OC and MGP share similar structural features, both in terms of protein domains and gene organization. OC gene is likely to have appeared from MGP through a tandem gene duplication that occurred concomitantly with the appearance of the bony vertebrates. Despite their relatively close relationship and the fact that both can bind calcium and affect mineralization, their functions are not redundant and they also have other unrelated functions. Interestingly, these two proteins appear to have followed quite different evolutionary strategies in order to acquire novel functionalities, with OC following a gene duplication strategy while MGP variability was obtained mostly by the use of multiple promoters and alternative splicing, leading to proteins with additional functional characteristics and alternative gene regulatory pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Gene duplications in prokaryotes can be associated with environmental adaptation

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    Lempicki Richard A

    2010-10-01

    Full Text Available Abstract Background Gene duplication is a normal evolutionary process. If there is no selective advantage in keeping the duplicated gene, it is usually reduced to a pseudogene and disappears from the genome. However, some paralogs are retained. These gene products are likely to be beneficial to the organism, e.g. in adaptation to new environmental conditions. The aim of our analysis is to investigate the properties of paralog-forming genes in prokaryotes, and to analyse the role of these retained paralogs by relating gene properties to life style of the corresponding prokaryotes. Results Paralogs were identified in a number of prokaryotes, and these paralogs were compared to singletons of persistent orthologs based on functional classification. This showed that the paralogs were associated with for example energy production, cell motility, ion transport, and defence mechanisms. A statistical overrepresentation analysis of gene and protein annotations was based on paralogs of the 200 prokaryotes with the highest fraction of paralog-forming genes. Biclustering of overrepresented gene ontology terms versus species was used to identify clusters of properties associated with clusters of species. The clusters were classified using similarity scores on properties and species to identify interesting clusters, and a subset of clusters were analysed by comparison to literature data. This analysis showed that paralogs often are associated with properties that are important for survival and proliferation of the specific organisms. This includes processes like ion transport, locomotion, chemotaxis and photosynthesis. However, the analysis also showed that the gene ontology terms sometimes were too general, imprecise or even misleading for automatic analysis. Conclusions Properties described by gene ontology terms identified in the overrepresentation analysis are often consistent with individual prokaryote lifestyles and are likely to give a competitive

  15. [Duplication of DNA--a mechanism for the development of new functionality of genes].

    Science.gov (United States)

    Maślanka, Roman; Zadrąg-Tęcza, Renata

    2015-01-01

    The amplification of DNA is considered as a mechanism for rapid evolution of organisms. Duplication can be especially advantageous in the case of changing environmental conditions. Whole genome duplication maintains the proper balance between gene expression. This seems to be the main reason why WGD is more favorable than duplication of the fragments of DNA. The polyploidy status disappear as a result of the loss of the majority of duplicated genes. The preservation of duplicated genes is associated with the development of their new functions. Polyploidization is often noted for plants. However due to sequencing technique, the duplications episodes are more frequently reports also for the other systematic taxa, including animals. The occurrence of ancient genome duplication is also considered for yeast Saccharomyces cerevisiae. The existence of two active copies of ribosomal protein genes can be a confirmation of this process. Development of the fermentation process might be one of the probable causes of the yeast genome duplication.

  16. Evolutionary Fates and Dynamic Functionalization of Young Duplicate Genes in Arabidopsis Genomes1[OPEN

    Science.gov (United States)

    Wang, Jun; Tao, Feng; Marowsky, Nicholas C.; Fan, Chuanzhu

    2016-01-01

    Gene duplication is a primary means to generate genomic novelties, playing an essential role in speciation and adaptation. Particularly in plants, a high abundance of duplicate genes has been maintained for significantly long periods of evolutionary time. To address the manner in which young duplicate genes were derived primarily from small-scale gene duplication and preserved in plant genomes and to determine the underlying driving mechanisms, we generated transcriptomes to produce the expression profiles of five tissues in Arabidopsis thaliana and the closely related species Arabidopsis lyrata and Capsella rubella. Based on the quantitative analysis metrics, we investigated the evolutionary processes of young duplicate genes in Arabidopsis. We determined that conservation, neofunctionalization, and specialization are three main evolutionary processes for Arabidopsis young duplicate genes. We explicitly demonstrated the dynamic functionalization of duplicate genes along the evolutionary time scale. Upon origination, duplicates tend to maintain their ancestral functions; but as they survive longer, they might be likely to develop distinct and novel functions. The temporal evolutionary processes and functionalization of plant duplicate genes are associated with their ancestral functions, dynamic DNA methylation levels, and histone modification abundances. Furthermore, duplicate genes tend to be initially expressed in pollen and then to gain more interaction partners over time. Altogether, our study provides novel insights into the dynamic retention processes of young duplicate genes in plant genomes. PMID:27485883

  17. Expression Divergence of Duplicate Genes in the Protein Kinase Superfamily in Pacific Oyster.

    Science.gov (United States)

    Gao, Dahai; Ko, Dennis C; Tian, Xinmin; Yang, Guang; Wang, Liuyang

    2015-01-01

    Gene duplication has been proposed to serve as the engine of evolutionary innovation. It is well recognized that eukaryotic genomes contain a large number of duplicated genes that evolve new functions or expression patterns. However, in mollusks, the evolutionary mechanisms underlying the divergence and the functional maintenance of duplicate genes remain little understood. In the present study, we performed a comprehensive analysis of duplicate genes in the protein kinase superfamily using whole genome and transcriptome data for the Pacific oyster. A total of 64 duplicated gene pairs were identified based on a phylogenetic approach and the reciprocal best BLAST method. By analyzing gene expression from RNA-seq data from 69 different developmental and stimuli-induced conditions (nine tissues, 38 developmental stages, eight dry treatments, seven heat treatments, and seven salty treatments), we found that expression patterns were significantly correlated for a number of duplicate gene pairs, suggesting the conservation of regulatory mechanisms following divergence. Our analysis also identified a subset of duplicate gene pairs with very high expression divergence, indicating that these gene pairs may have been subjected to transcriptional subfunctionalization or neofunctionalization after the initial duplication events. Further analysis revealed a significant correlation between expression and sequence divergence (as revealed by synonymous or nonsynonymous substitution rates) under certain conditions. Taken together, these results provide evidence for duplicate gene sequence and expression divergence in the Pacific oyster, accompanying its adaptation to harsh environments. Our results provide new insights into the evolution of duplicate genes and their expression levels in the Pacific oyster.

  18. Neutral and Non-Neutral Evolution of Duplicated Genes with Gene Conversion

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    Jeffrey A. Fawcett

    2011-02-01

    Full Text Available Gene conversion is one of the major mutational mechanisms involved in the DNA sequence evolution of duplicated genes. It contributes to create unique patters of DNA polymorphism within species and divergence between species. A typical pattern is so-called concerted evolution, in which the divergence between duplicates is maintained low for a long time because of frequent exchanges of DNA fragments. In addition, gene conversion affects the DNA evolution of duplicates in various ways especially when selection operates. Here, we review theoretical models to understand the evolution of duplicates in both neutral and non-neutral cases. We also explain how these theories contribute to interpreting real polymorphism and divergence data by using some intriguing examples.

  19. Duplication and Diversification of the Hypoxia-Inducible IGFBP-1 Gene in Zebrafish

    DEFF Research Database (Denmark)

    Kamei, Hiroyasu; Lu, Ling; Jiao, Shuang

    2008-01-01

    Background: Gene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish is uniquely positioned to provide insight into the process of functional gene evolution due to its amenabilit...

  20. Divergence of Recently Duplicated Mg-Type MADS-Box Genes in Petunia

    NARCIS (Netherlands)

    Bemer, M.; Gordon, J.; Weterings, K.; Angenent, G.C.

    2010-01-01

    The MADS-box transcription factor family has expanded considerably in plants via gene and genome duplications and can be subdivided into type I and MIKC-type genes. The two gene classes show a different evolutionary history. Whereas the MIKC-type genes originated during ancient genome duplications,

  1. Biased exonization of transposed elements in duplicated genes: A lesson from the TIF-IA gene

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    Shomron Noam

    2007-11-01

    Full Text Available Abstract Background Gene duplication and exonization of intronic transposed elements are two mechanisms that enhance genomic diversity. We examined whether there is less selection against exonization of transposed elements in duplicated genes than in single-copy genes. Results Genome-wide analysis of exonization of transposed elements revealed a higher rate of exonization within duplicated genes relative to single-copy genes. The gene for TIF-IA, an RNA polymerase I transcription initiation factor, underwent a humanoid-specific triplication, all three copies of the gene are active transcriptionally, although only one copy retains the ability to generate the TIF-IA protein. Prior to TIF-IA triplication, an Alu element was inserted into the first intron. In one of the non-protein coding copies, this Alu is exonized. We identified a single point mutation leading to exonization in one of the gene duplicates. When this mutation was introduced into the TIF-IA coding copy, exonization was activated and the level of the protein-coding mRNA was reduced substantially. A very low level of exonization was detected in normal human cells. However, this exonization was abundant in most leukemia cell lines evaluated, although the genomic sequence is unchanged in these cancerous cells compared to normal cells. Conclusion The definition of the Alu element within the TIF-IA gene as an exon is restricted to certain types of cancers; the element is not exonized in normal human cells. These results further our understanding of the delicate interplay between gene duplication and alternative splicing and of the molecular evolutionary mechanisms leading to genetic innovations. This implies the existence of purifying selection against exonization in single copy genes, with duplicate genes free from such constrains.

  2. Accelerated evolution after gene duplication: a time-dependent process affecting just one copy.

    Science.gov (United States)

    Pegueroles, Cinta; Laurie, Steve; Albà, M Mar

    2013-08-01

    Gene duplication is widely regarded as a major mechanism modeling genome evolution and function. However, the mechanisms that drive the evolution of the two, initially redundant, gene copies are still ill defined. Many gene duplicates experience evolutionary rate acceleration, but the relative contribution of positive selection and random drift to the retention and subsequent evolution of gene duplicates, and for how long the molecular clock may be distorted by these processes, remains unclear. Focusing on rodent genes that duplicated before and after the mouse and rat split, we find significantly increased sequence divergence after duplication in only one of the copies, which in nearly all cases corresponds to the novel daughter copy, independent of the mechanism of duplication. We observe that the evolutionary rate of the accelerated copy, measured as the ratio of nonsynonymous to synonymous substitutions, is on average 5-fold higher in the period spanning 4-12 My after the duplication than it was before the duplication. This increase can be explained, at least in part, by the action of positive selection according to the results of the maximum likelihood-based branch-site test. Subsequently, the rate decelerates until purifying selection completely returns to preduplication levels. Reversion to the original rates has already been accomplished 40.5 My after the duplication event, corresponding to a genetic distance of about 0.28 synonymous substitutions per site. Differences in tissue gene expression patterns parallel those of substitution rates, reinforcing the role of neofunctionalization in explaining the evolution of young gene duplicates.

  3. Restriction and Recruitment—Gene Duplication and the Origin and Evolution of Snake Venom Toxins

    OpenAIRE

    Hargreaves, Adam D; Swain, Martin T.; Matthew J. Hegarty; Logan, Darren W; Mulley, John F

    2014-01-01

    Snake venom has been hypothesized to have originated and diversified through a process that involves duplication of genes encoding body proteins with subsequent recruitment of the copy to the venom gland, where natural selection acts to develop or increase toxicity. However, gene duplication is known to be a rare event in vertebrate genomes, and the recruitment of duplicated genes to a novel expression domain (neofunctionalization) is an even rarer process that requires the evolution of novel...

  4. Genome-wide analysis of homeobox gene family in legumes: identification, gene duplication and expression profiling.

    Science.gov (United States)

    Bhattacharjee, Annapurna; Ghangal, Rajesh; Garg, Rohini; Jain, Mukesh

    2015-01-01

    Homeobox genes encode transcription factors that are known to play a major role in different aspects of plant growth and development. In the present study, we identified homeobox genes belonging to 14 different classes in five legume species, including chickpea, soybean, Medicago, Lotus and pigeonpea. The characteristic differences within homeodomain sequences among various classes of homeobox gene family were quite evident. Genome-wide expression analysis using publicly available datasets (RNA-seq and microarray) indicated that homeobox genes are differentially expressed in various tissues/developmental stages and under stress conditions in different legumes. We validated the differential expression of selected chickpea homeobox genes via quantitative reverse transcription polymerase chain reaction. Genome duplication analysis in soybean indicated that segmental duplication has significantly contributed in the expansion of homeobox gene family. The Ka/Ks ratio of duplicated homeobox genes in soybean showed that several members of this family have undergone purifying selection. Moreover, expression profiling indicated that duplicated genes might have been retained due to sub-functionalization. The genome-wide identification and comprehensive gene expression profiling of homeobox gene family members in legumes will provide opportunities for functional analysis to unravel their exact role in plant growth and development.

  5. Are duplicated genes responsible for anthracnose resistance in common bean?

    Science.gov (United States)

    Costa, Larissa Carvalho; Nalin, Rafael Storto; Ramalho, Magno Antonio Patto; de Souza, Elaine Aparecida

    2017-01-01

    The race 65 of Colletotrichum lindemuthianum, etiologic agent of anthracnose in common bean, is distributed worldwide, having great importance in breeding programs for anthracnose resistance. Several resistance alleles have been identified promoting resistance to this race. However, the variability that has been detected within race has made it difficult to obtain cultivars with durable resistance, because cultivars may have different reactions to each strain of race 65. Thus, this work aimed at studying the resistance inheritance of common bean lines to different strains of C. lindemuthianum, race 65. We used six C. lindemuthianum strains previously characterized as belonging to the race 65 through the international set of differential cultivars of anthracnose and nine commercial cultivars, adapted to the Brazilian growing conditions and with potential ability to discriminate the variability within this race. To obtain information on the resistance inheritance related to nine commercial cultivars to six strains of race 65, these cultivars were crossed two by two in all possible combinations, resulting in 36 hybrids. Segregation in the F2 generations revealed that the resistance to each strain is conditioned by two independent genes with the same function, suggesting that they are duplicated genes, where the dominant allele promotes resistance. These results indicate that the specificity between host resistance genes and pathogen avirulence genes is not limited to races, it also occurs within strains of the same race. Further research may be carried out in order to establish if the alleles identified in these cultivars are different from those described in the literature.

  6. Duplication of pilus gene complexes of Haemophilus influenzae biogroup aegyptius.

    Science.gov (United States)

    Read, T D; Dowdell, M; Satola, S W; Farley, M M

    1996-11-01

    Brazilian purpuric fever (BPF) is a recently described pediatric septicemia caused by a strain of Haemophilus influenzae biogroup aegyptius. The pilus specified by this bacterium may be important in BPF pathogenesis, enhancing attachment to host tissue. Here, we report the cloning of two haf (for H. influenzae biogroup aegyptius fimbriae) gene clusters from a cosmid library of strain F3031. We sequenced a 6.8-kb segment of the haf1 cluster and identified five genes (hafA to hafE). The predicted protein products, HafA to HafD, are 72, 95, 98, and 90% similar, respectively, to HifA to HifD of the closely related H. influenzae type b pilus. Strikingly, the putative pilus adhesion, HifE, shares only 44% identity with HafE, suggesting that the proteins may differ in receptor specificity. Insertion of a mini-gammadelta transposon in the hafE gene eliminated hemadsorption. The nucleotide sequences of the haf1 and haf2 clusters are more than 99% identical. Using the recently published sequence of the H. influenzae Rd genome, we determined that the haf1 complex lies at a unique position in the chromosome between the pmbA gene and a hypothetical open reading frame, HI1153. The location of the haf2 cluster, inserted between the purE and pepN genes, is analogous to the hif genes on H. influenzae type b. BPF fimbrial phase switching appears to involve slip-strand mispairing of repeated dinucleotides in the pilus promoter. The BPF-associated H. influenzae biogroup aegyptius pilus system generally resembles other H. influenzae, but the possession of a second fimbrial gene cluster, which appears to have arisen by a recent duplication event, and the novel sequence of the HafE adhesin may be significant in the unusual pathogenesis of BPF.

  7. Comparative Inference of Duplicated Genes Produced by Polyploidization in Soybean Genome

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    Yanmei Yang

    2013-01-01

    Full Text Available Soybean (Glycine max is one of the most important crop plants for providing protein and oil. It is important to investigate soybean genome for its economic and scientific value. Polyploidy is a widespread and recursive phenomenon during plant evolution, and it could generate massive duplicated genes which is an important resource for genetic innovation. Improved sequence alignment criteria and statistical analysis are used to identify and characterize duplicated genes produced by polyploidization in soybean. Based on the collinearity method, duplicated genes by whole genome duplication account for 70.3% in soybean. From the statistical analysis of the molecular distances between duplicated genes, our study indicates that the whole genome duplication event occurred more than once in the genome evolution of soybean, which is often distributed near the ends of chromosomes.

  8. Adaptive evolution of genes duplicated from the Drosophila pseudoobscura neo-X chromosome.

    Science.gov (United States)

    Meisel, Richard P; Hilldorfer, Benedict B; Koch, Jessica L; Lockton, Steven; Schaeffer, Stephen W

    2010-08-01

    Drosophila X chromosomes are disproportionate sources of duplicated genes, and these duplications are usually the result of retrotransposition of X-linked genes to the autosomes. The excess duplication is thought to be driven by natural selection for two reasons: X chromosomes are inactivated during spermatogenesis, and the derived copies of retroposed duplications tend to be testis expressed. Therefore, autosomal derived copies of retroposed genes provide a mechanism for their X-linked paralogs to "escape" X inactivation. Once these duplications have fixed, they may then be selected for male-specific functions. Throughout the evolution of the Drosophila genus, autosomes have fused with X chromosomes along multiple lineages giving rise to neo-X chromosomes. There has also been excess duplication from the two independent neo-X chromosomes that have been examined--one that occurred prior to the common ancestor of the willistoni species group and another that occurred along the lineage leading to Drosophila pseudoobscura. To determine what role natural selection plays in the evolution of genes duplicated from the D. pseudoobscura neo-X chromosome, we analyzed DNA sequence divergence between paralogs, polymorphism within each copy, and the expression profiles of these duplicated genes. We found that the derived copies of all duplicated genes have elevated nonsynonymous polymorphism, suggesting that they are under relaxed selective constraints. The derived copies also tend to have testis- or male-biased expression profiles regardless of their chromosome of origin. Genes duplicated from the neo-X chromosome appear to be under less constraints than those duplicated from other chromosome arms. We also find more evidence for historical adaptive evolution in genes duplicated from the neo-X chromosome, suggesting that they are under a unique selection regime in which elevated nonsynonymous polymorphism provides a large reservoir of functional variants, some of which are fixed

  9. The Evolutionary Relationship between Alternative Splicing and Gene Duplication

    Science.gov (United States)

    Iñiguez, Luis P.; Hernández, Georgina

    2017-01-01

    The protein diversity that exists today has resulted from various evolutionary processes. It is well known that gene duplication (GD) along with the accumulation of mutations are responsible, among other factors, for an increase in the number of different proteins. The gene structure in eukaryotes requires the removal of non-coding sequences, introns, to produce mature mRNAs. This process, known as cis-splicing, referred to here as splicing, is regulated by several factors which can lead to numerous splicing arrangements, commonly designated as alternative splicing (AS). AS, producing several transcripts isoforms form a single gene, also increases the protein diversity. However, the evolution and manner for increasing protein variation differs between AS and GD. An important question is how are patterns of AS affected after a GD event. Here, we review the current knowledge of AS and GD, focusing on their evolutionary relationship. These two processes are now considered the main contributors to the increasing protein diversity and therefore their relationship is a relevant, yet understudied, area of evolutionary study. PMID:28261262

  10. Evolution of vertebrate central nervous system is accompanied by novel expression changes of duplicate genes.

    Science.gov (United States)

    Chen, Yuan; Ding, Yun; Zhang, Zuming; Wang, Wen; Chen, Jun-Yuan; Ueno, Naoto; Mao, Bingyu

    2011-12-20

    The evolution of the central nervous system (CNS) is one of the most striking changes during the transition from invertebrates to vertebrates. As a major source of genetic novelties, gene duplication might play an important role in the functional innovation of vertebrate CNS. In this study, we focused on a group of CNS-biased genes that duplicated during early vertebrate evolution. We investigated the tempo-spatial expression patterns of 33 duplicate gene families and their orthologs during the embryonic development of the vertebrate Xenopus laevis and the cephalochordate Brachiostoma belcheri. Almost all the identified duplicate genes are differentially expressed in the CNS in Xenopus embryos, and more than 50% and 30% duplicate genes are expressed in the telencephalon and mid-hindbrain boundary, respectively, which are mostly considered as two innovations in the vertebrate CNS. Interestingly, more than 50% of the amphioxus orthologs do not show apparent expression in the CNS in amphioxus embryos as detected by in situ hybridization, indicating that some of the vertebrate CNS-biased duplicate genes might arise from non-CNS genes in invertebrates. Our data accentuate the functional contribution of gene duplication in the CNS evolution of vertebrate and uncover an invertebrate non-CNS history for some vertebrate CNS-biased duplicate genes. Copyright © 2011. Published by Elsevier Ltd.

  11. Duplication of OsHAP family genes and their association with heading date in rice.

    Science.gov (United States)

    Li, Qiuping; Yan, Wenhao; Chen, Huaxia; Tan, Cong; Han, Zhongmin; Yao, Wen; Li, Guangwei; Yuan, Mengqi; Xing, Yongzhong

    2016-03-01

    Heterotrimeric Heme Activator Protein (HAP) family genes are involved in the regulation of flowering in plants. It is not clear how many HAP genes regulate heading date in rice. In this study, we identified 35 HAP genes, including seven newly identified genes, and performed gene duplication and candidate gene-based association analyses. Analyses showed that segmental duplication and tandem duplication are the main mechanisms of HAP gene duplication. Expression profiling and functional identification indicated that duplication probably diversifies the functions of HAP genes. A nucleotide diversity analysis revealed that 13 HAP genes underwent selection. A candidate gene-based association analysis detected four HAP genes related to heading date. An investigation of transgenic plants or mutants of 23 HAP genes confirmed that overexpression of at least four genes delayed heading date under long-day conditions, including the previously cloned Ghd8/OsHAP3H. Our results indicate that the large number of HAP genes in rice was mainly produced by gene duplication, and a few HAP genes function to regulate heading date. Selection of HAP genes is probably caused by their diverse functions rather than regulation of heading.

  12. Divergence of gene body DNA methylation and evolution of plant duplicate genes.

    Directory of Open Access Journals (Sweden)

    Jun Wang

    Full Text Available It has been shown that gene body DNA methylation is associated with gene expression. However, whether and how deviation of gene body DNA methylation between duplicate genes can influence their divergence remains largely unexplored. Here, we aim to elucidate the potential role of gene body DNA methylation in the fate of duplicate genes. We identified paralogous gene pairs from Arabidopsis and rice (Oryza sativa ssp. japonica genomes and reprocessed their single-base resolution methylome data. We show that methylation in paralogous genes nonlinearly correlates with several gene properties including exon number/gene length, expression level and mutation rate. Further, we demonstrated that divergence of methylation level and pattern in paralogs indeed positively correlate with their sequence and expression divergences. This result held even after controlling for other confounding factors known to influence the divergence of paralogs. We observed that methylation level divergence might be more relevant to the expression divergence of paralogs than methylation pattern divergence. Finally, we explored the mechanisms that might give rise to the divergence of gene body methylation in paralogs. We found that exonic methylation divergence more closely correlates with expression divergence than intronic methylation divergence. We show that genomic environments (e.g., flanked by transposable elements and repetitive sequences of paralogs generated by various duplication mechanisms are associated with the methylation divergence of paralogs. Overall, our results suggest that the changes in gene body DNA methylation could provide another avenue for duplicate genes to develop differential expression patterns and undergo different evolutionary fates in plant genomes.

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

    Science.gov (United States)

    Bao, Yongbo

    2017-01-01

    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. PMID:28338988

  14. Global analysis of human duplicated genes reveals the relative importance of whole-genome duplicates originated in the early vertebrate evolution.

    Science.gov (United States)

    Acharya, Debarun; Ghosh, Tapash C

    2016-01-22

    Gene duplication is a genetic mutation that creates functionally redundant gene copies that are initially relieved from selective pressures and may adapt themselves to new functions with time. The levels of gene duplication may vary from small-scale duplication (SSD) to whole genome duplication (WGD). Studies with yeast revealed ample differences between these duplicates: Yeast WGD pairs were functionally more similar, less divergent in subcellular localization and contained a lesser proportion of essential genes. In this study, we explored the differences in evolutionary genomic properties of human SSD and WGD genes, with the identifiable human duplicates coming from the two rounds of whole genome duplication occurred early in vertebrate evolution. We observed that these two groups of duplicates were also dissimilar in terms of their evolutionary and genomic properties. But interestingly, this is not like the same observed in yeast. The human WGDs were found to be functionally less similar, diverge more in subcellular level and contain a higher proportion of essential genes than the SSDs, all of which are opposite from yeast. Additionally, we explored that human WGDs were more divergent in their gene expression profile, have higher multifunctionality and are more often associated with disease, and are evolutionarily more conserved than human SSDs. Our study suggests that human WGD duplicates are more divergent and entails the adaptation of WGDs to novel and important functions that consequently lead to their evolutionary conservation in the course of evolution.

  15. Consensus properties and their large-scale applications for the gene duplication problem.

    Science.gov (United States)

    Moon, Jucheol; Lin, Harris T; Eulenstein, Oliver

    2016-06-01

    Solving the gene duplication problem is a classical approach for species tree inference from gene trees that are confounded by gene duplications. This problem takes a collection of gene trees and seeks a species tree that implies the minimum number of gene duplications. Wilkinson et al. posed the conjecture that the gene duplication problem satisfies the desirable Pareto property for clusters. That is, for every instance of the problem, all clusters that are commonly present in the input gene trees of this instance, called strict consensus, will also be found in every solution to this instance. We prove that this conjecture does not generally hold. Despite this negative result we show that the gene duplication problem satisfies a weaker version of the Pareto property where the strict consensus is found in at least one solution (rather than all solutions). This weaker property contributes to our design of an efficient scalable algorithm for the gene duplication problem. We demonstrate the performance of our algorithm in analyzing large-scale empirical datasets. Finally, we utilize the algorithm to evaluate the accuracy of standard heuristics for the gene duplication problem using simulated datasets.

  16. Buffering by gene duplicates: an analysis of molecular correlates and evolutionary conservation

    Directory of Open Access Journals (Sweden)

    Vogel Christine

    2008-12-01

    Full Text Available Abstract Background One mechanism to account for robustness against gene knockouts or knockdowns is through buffering by gene duplicates, but the extent and general correlates of this process in organisms is still a matter of debate. To reveal general trends of this process, we provide a comprehensive comparison of gene essentiality, duplication and buffering by duplicates across seven bacteria (Mycoplasma genitalium, Bacillus subtilis, Helicobacter pylori, Haemophilus influenzae, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Escherichia coli, and four eukaryotes (Saccharomyces cerevisiae (yeast, Caenorhabditis elegans (worm, Drosophila melanogaster (fly, Mus musculus (mouse. Results In nine of the eleven organisms, duplicates significantly increase chances of survival upon gene deletion (P-value ≤ 0.05, but only by up to 13%. Given that duplicates make up to 80% of eukaryotic genomes, the small contribution is surprising and points to dominant roles of other buffering processes, such as alternative metabolic pathways. The buffering capacity of duplicates appears to be independent of the degree of gene essentiality and tends to be higher for genes with high expression levels. For example, buffering capacity increases to 23% amongst highly expressed genes in E. coli. Sequence similarity and the number of duplicates per gene are weak predictors of the duplicate's buffering capacity. In a case study we show that buffering gene duplicates in yeast and worm are somewhat more similar in their functions than non-buffering duplicates and have increased transcriptional and translational activity. Conclusion In sum, the extent of gene essentiality and buffering by duplicates is not conserved across organisms and does not correlate with the organisms' apparent complexity. This heterogeneity goes beyond what would be expected from differences in experimental approaches alone. Buffering by duplicates contributes to robustness in several organisms

  17. Subfunctionalization of duplicated zebrafish pax6 genes by cis-regulatory divergence

    National Research Council Canada - National Science Library

    Kleinjan, Dirk A; Bancewicz, Ruth M; Gautier, Philippe; Dahm, Ralf; Schonthaler, Helia B; Damante, Giuseppe; Seawright, Anne; Hever, Ann M; Yeyati, Patricia L; van Heyningen, Veronica; Coutinho, Pedro

    2008-01-01

    Gene duplication is a major driver of evolutionary divergence. In most vertebrates a single PAX6 gene encodes a transcription factor required for eye, brain, olfactory system, and pancreas development...

  18. The evolutionary fate of alternatively spliced homologous exons after gene duplication.

    Science.gov (United States)

    Abascal, Federico; Tress, Michael L; Valencia, Alfonso

    2015-04-29

    Alternative splicing and gene duplication are the two main processes responsible for expanding protein functional diversity. Although gene duplication can generate new genes and alternative splicing can introduce variation through alternative gene products, the interplay between the two processes is complex and poorly understood. Here, we have carried out a study of the evolution of alternatively spliced exons after gene duplication to better understand the interaction between the two processes. We created a manually curated set of 97 human genes with mutually exclusively spliced homologous exons and analyzed the evolution of these exons across five distantly related vertebrates (lamprey, spotted gar, zebrafish, fugu, and coelacanth). Most of these exons had an ancient origin (more than 400 Ma). We found examples supporting two extreme evolutionary models for the behaviour of homologous axons after gene duplication. We observed 11 events in which gene duplication was accompanied by splice isoform separation, that is, each paralog specifically conserved just one distinct ancestral homologous exon. At other extreme, we identified genes in which the homologous exons were always conserved within paralogs, suggesting that the alternative splicing event cannot easily be separated from the function in these genes. That many homologous exons fall in between these two extremes highlights the diversity of biological systems and suggests that the subtle balance between alternative splicing and gene duplication is adjusted to the specific cellular context of each gene. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Gene duplication and divergence affecting drug content in Cannabis sativa.

    Science.gov (United States)

    Weiblen, George D; Wenger, Jonathan P; Craft, Kathleen J; ElSohly, Mahmoud A; Mehmedic, Zlatko; Treiber, Erin L; Marks, M David

    2015-12-01

    Cannabis sativa is an economically important source of durable fibers, nutritious seeds, and psychoactive drugs but few economic plants are so poorly understood genetically. Marijuana and hemp were crossed to evaluate competing models of cannabinoid inheritance and to explain the predominance of tetrahydrocannabinolic acid (THCA) in marijuana compared with cannabidiolic acid (CBDA) in hemp. Individuals in the resulting F2 population were assessed for differential expression of cannabinoid synthase genes and were used in linkage mapping. Genetic markers associated with divergent cannabinoid phenotypes were identified. Although phenotypic segregation and a major quantitative trait locus (QTL) for the THCA/CBDA ratio were consistent with a simple model of codominant alleles at a single locus, the diversity of THCA and CBDA synthase sequences observed in the mapping population, the position of enzyme coding loci on the map, and patterns of expression suggest multiple linked loci. Phylogenetic analysis further suggests a history of duplication and divergence affecting drug content. Marijuana is distinguished from hemp by a nonfunctional CBDA synthase that appears to have been positively selected to enhance psychoactivity. An unlinked QTL for cannabinoid quantity may also have played a role in the recent escalation of drug potency.

  20. Gene duplications and losses among vertebrate deoxyribonucleoside kinases of the non-TK1 Family

    DEFF Research Database (Denmark)

    Mutahir, Zeeshan; Christiansen, Louise Slot; Clausen, Anders R.;

    2016-01-01

    , among vertebrates only four mammalian dNKs have been studied for their substrate specificity and kinetic properties. However, some vertebrates, such as fish, frogs, and birds, apparently possess a duplicated homolog of deoxycytidine kinase (dCK). In this study, we characterized a family of d......CK/deoxyguanosine kinase (dGK)-like enzymes from a frog Xenopus laevis and a bird Gallus gallus. We showed that X. laevis has a duplicated dCK gene and a dGK gene, whereas G. gallus has a duplicated dCK gene but has lost the dGK gene. We cloned, expressed, purified, and subsequently determined the kinetic parameters...

  1. The roles of whole-genome and small-scale duplications in the functional specialization of Saccharomyces cerevisiae genes.

    Directory of Open Access Journals (Sweden)

    Mario A Fares

    Full Text Available Researchers have long been enthralled with the idea that gene duplication can generate novel functions, crediting this process with great evolutionary importance. Empirical data shows that whole-genome duplications (WGDs are more likely to be retained than small-scale duplications (SSDs, though their relative contribution to the functional fate of duplicates remains unexplored. Using the map of genetic interactions and the re-sequencing of 27 Saccharomyces cerevisiae genomes evolving for 2,200 generations we show that SSD-duplicates lead to neo-functionalization while WGD-duplicates partition ancestral functions. This conclusion is supported by: (a SSD-duplicates establish more genetic interactions than singletons and WGD-duplicates; (b SSD-duplicates copies share more interaction-partners than WGD-duplicates copies; (c WGD-duplicates interaction partners are more functionally related than SSD-duplicates partners; (d SSD-duplicates gene copies are more functionally divergent from one another, while keeping more overlapping functions, and diverge in their sub-cellular locations more than WGD-duplicates copies; and (e SSD-duplicates complement their functions to a greater extent than WGD-duplicates. We propose a novel model that uncovers the complexity of evolution after gene duplication.

  2. The Roles of Whole-Genome and Small-Scale Duplications in the Functional Specialization of Saccharomyces cerevisiae Genes

    Science.gov (United States)

    Fares, Mario A.; Keane, Orla M.; Toft, Christina; Carretero-Paulet, Lorenzo; Jones, Gary W.

    2013-01-01

    Researchers have long been enthralled with the idea that gene duplication can generate novel functions, crediting this process with great evolutionary importance. Empirical data shows that whole-genome duplications (WGDs) are more likely to be retained than small-scale duplications (SSDs), though their relative contribution to the functional fate of duplicates remains unexplored. Using the map of genetic interactions and the re-sequencing of 27 Saccharomyces cerevisiae genomes evolving for 2,200 generations we show that SSD-duplicates lead to neo-functionalization while WGD-duplicates partition ancestral functions. This conclusion is supported by: (a) SSD-duplicates establish more genetic interactions than singletons and WGD-duplicates; (b) SSD-duplicates copies share more interaction-partners than WGD-duplicates copies; (c) WGD-duplicates interaction partners are more functionally related than SSD-duplicates partners; (d) SSD-duplicates gene copies are more functionally divergent from one another, while keeping more overlapping functions, and diverge in their sub-cellular locations more than WGD-duplicates copies; and (e) SSD-duplicates complement their functions to a greater extent than WGD–duplicates. We propose a novel model that uncovers the complexity of evolution after gene duplication. PMID:23300483

  3. Tandem gene arrays in Trypanosoma brucei: Comparative phylogenomic analysis of duplicate sequence variation

    Directory of Open Access Journals (Sweden)

    Jackson Andrew P

    2007-04-01

    Full Text Available Abstract Background The genome sequence of the protistan parasite Trypanosoma brucei contains many tandem gene arrays. Gene duplicates are created through tandem duplication and are expressed through polycistronic transcription, suggesting that the primary purpose of long, tandem arrays is to increase gene dosage in an environment where individual gene promoters are absent. This report presents the first account of the tandem gene arrays in the T. brucei genome, employing several related genome sequences to establish how variation is created and removed. Results A systematic survey of tandem gene arrays showed that substantial sequence variation existed across the genome; variation from different regions of an array often produced inconsistent phylogenetic affinities. Phylogenetic relationships of gene duplicates were consistent with concerted evolution being a widespread homogenising force. However, tandem duplicates were not usually identical; therefore, any homogenising effect was coincident with divergence among duplicates. Allelic gene conversion was detected using various criteria and was apparently able to both remove and introduce sequence variation. Tandem arrays containing structural heterogeneity demonstrated how sequence homogenisation and differentiation can occur within a single locus. Conclusion The use of multiple genome sequences in a comparative analysis of tandem gene arrays identified substantial sequence variation among gene duplicates. The distribution of sequence variation is determined by a dynamic balance of conservative and innovative evolutionary forces. Gene trees from various species showed that intraspecific duplicates evolve in concert, perhaps through frequent gene conversion, although this does not prevent sequence divergence, especially where structural heterogeneity physically separates a duplicate from its neighbours. In describing dynamics of sequence variation that have consequences beyond gene dosage, this

  4. Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster

    Directory of Open Access Journals (Sweden)

    Jakobek Judy L

    2007-07-01

    Full Text Available Abstract Background The biosynthesis of aflatoxin (AF involves over 20 enzymatic reactions in a complex polyketide pathway that converts acetate and malonate to the intermediates sterigmatocystin (ST and O-methylsterigmatocystin (OMST, the respective penultimate and ultimate precursors of AF. Although these precursors are chemically and structurally very similar, their accumulation differs at the species level for Aspergilli. Notable examples are A. nidulans that synthesizes only ST, A. flavus that makes predominantly AF, and A. parasiticus that generally produces either AF or OMST. Whether these differences are important in the evolutionary/ecological processes of species adaptation and diversification is unknown. Equally unknown are the specific genomic mechanisms responsible for ordering and clustering of genes in the AF pathway of Aspergillus. Results To elucidate the mechanisms that have driven formation of these clusters, we performed systematic searches of aflatoxin cluster homologs across five Aspergillus genomes. We found a high level of gene duplication and identified seven modules consisting of highly correlated gene pairs (aflA/aflB, aflR/aflS, aflX/aflY, aflF/aflE, aflT/aflQ, aflC/aflW, and aflG/aflL. With the exception of A. nomius, contrasts of mean Ka/Ks values across all cluster genes showed significant differences in selective pressure between section Flavi and non-section Flavi species. A. nomius mean Ka/Ks values were more similar to partial clusters in A. fumigatus and A. terreus. Overall, mean Ka/Ks values were significantly higher for section Flavi than for non-section Flavi species. Conclusion Our results implicate several genomic mechanisms in the evolution of ST, OMST and AF cluster genes. Gene modules may arise from duplications of a single gene, whereby the function of the pre-duplication gene is retained in the copy (aflF/aflE or the copies may partition the ancestral function (aflA/aflB. In some gene modules, the

  5. Effect of Incomplete Lineage Sorting On Tree-Reconciliation-Based Inference of Gene Duplication.

    Science.gov (United States)

    Zheng, Yu; Zhang, Louxin

    2014-01-01

    In the tree reconciliation approach to infer the duplication history of a gene family, the gene (family) tree is compared to the corresponding species tree. Incomplete lineage sorting (ILS) gives rise to stochastic variation in the topology of a gene tree and hence likely introduces false duplication events when a tree reconciliation method is used. We quantify the effect of ILS on gene duplication inference in a species tree in terms of the expected number of false duplication events inferred from reconciling a random gene tree, which occurs with a probability predicted in coalescent theory, and the species tree. We computationally examine the relationship between the effect of ILS on duplication inference in a species tree and its topological parameters. Our findings suggest that ILS may cause non-negligible bias on duplication inference, particularly on an asymmetric species tree. Hence, when gene duplication is inferred via tree reconciliation or any other approach that takes gene tree topology into account, the ILS-induced bias should be examined cautiously.

  6. Pinda: a web service for detection and analysis of intraspecies gene duplication events.

    Science.gov (United States)

    Kontopoulos, Dimitrios-Georgios; Glykos, Nicholas M

    2013-09-01

    We present Pinda, a Web service for the detection and analysis of possible duplications of a given protein or DNA sequence within a source species. Pinda fully automates the whole gene duplication detection procedure, from performing the initial similarity searches, to generating the multiple sequence alignments and the corresponding phylogenetic trees, to bootstrapping the trees and producing a Z-score-based list of duplication candidates for the input sequence. Pinda has been cross-validated using an extensive set of known and bibliographically characterized duplication events. The service facilitates the automatic and dependable identification of gene duplication events, using some of the most successful bioinformatics software to perform an extensive analysis protocol. Pinda will prove of use for the analysis of newly discovered genes and proteins, thus also assisting the study of recently sequenced genomes. The service's location is http://orion.mbg.duth.gr/Pinda. The source code is freely available via https://github.com/dgkontopoulos/Pinda/.

  7. Comparative study of human mitochondrial proteome reveals extensive protein subcellular relocalization after gene duplications

    Directory of Open Access Journals (Sweden)

    Huang Yong

    2009-11-01

    Full Text Available Abstract Background Gene and genome duplication is the principle creative force in evolution. Recently, protein subcellular relocalization, or neolocalization was proposed as one of the mechanisms responsible for the retention of duplicated genes. This hypothesis received support from the analysis of yeast genomes, but has not been tested thoroughly on animal genomes. In order to evaluate the importance of subcellular relocalizations for retention of duplicated genes in animal genomes, we systematically analyzed nuclear encoded mitochondrial proteins in the human genome by reconstructing phylogenies of mitochondrial multigene families. Results The 456 human mitochondrial proteins selected for this study were clustered into 305 gene families including 92 multigene families. Among the multigene families, 59 (64% consisted of both mitochondrial and cytosolic (non-mitochondrial proteins (mt-cy families while the remaining 33 (36% were composed of mitochondrial proteins (mt-mt families. Phylogenetic analyses of mt-cy families revealed three different scenarios of their neolocalization following gene duplication: 1 relocalization from mitochondria to cytosol, 2 from cytosol to mitochondria and 3 multiple subcellular relocalizations. The neolocalizations were most commonly enabled by the gain or loss of N-terminal mitochondrial targeting signals. The majority of detected subcellular relocalization events occurred early in animal evolution, preceding the evolution of tetrapods. Mt-mt protein families showed a somewhat different pattern, where gene duplication occurred more evenly in time. However, for both types of protein families, most duplication events appear to roughly coincide with two rounds of genome duplications early in vertebrate evolution. Finally, we evaluated the effects of inaccurate and incomplete annotation of mitochondrial proteins and found that our conclusion of the importance of subcellular relocalization after gene duplication on

  8. Spider Transcriptomes Identify Ancient Large-Scale Gene Duplication Event Potentially Important in Silk Gland Evolution.

    Science.gov (United States)

    Clarke, Thomas H; Garb, Jessica E; Hayashi, Cheryl Y; Arensburger, Peter; Ayoub, Nadia A

    2015-06-08

    The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (order Scorpionida) and spiders (order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk glands. Transcripts that are expressed exclusively or primarily within black widow silk glands are more likely to have a paralog descended from the ancient duplication event and have elevated amino acid replacement rates compared with other transcripts. Thus, an ancient large-scale gene duplication event within the spider lineage was likely an important source of molecular novelty during the evolution of silk gland-specific expression. This duplication event may have provided genetic material for subsequent silk gland diversification in the true spiders (Araneomorphae). © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  9. Extensive local gene duplication and functional divergence among paralogs in Atlantic salmon.

    Science.gov (United States)

    Warren, Ian A; Ciborowski, Kate L; Casadei, Elisa; Hazlerigg, David G; Martin, Sam; Jordan, William C; Sumner, Seirian

    2014-06-19

    Many organisms can generate alternative phenotypes from the same genome, enabling individuals to exploit diverse and variable environments. A prevailing hypothesis is that such adaptation has been favored by gene duplication events, which generate redundant genomic material that may evolve divergent functions. Vertebrate examples of recent whole-genome duplications are sparse although one example is the salmonids, which have undergone a whole-genome duplication event within the last 100 Myr. The life-cycle of the Atlantic salmon, Salmo salar, depends on the ability to produce alternating phenotypes from the same genome, to facilitate migration and maintain its anadromous life history. Here, we investigate the hypothesis that genome-wide and local gene duplication events have contributed to the salmonid adaptation. We used high-throughput sequencing to characterize the transcriptomes of three key organs involved in regulating migration in S. salar: Brain, pituitary, and olfactory epithelium. We identified over 10,000 undescribed S. salar sequences and designed an analytic workflow to distinguish between paralogs originating from local gene duplication events or from whole-genome duplication events. These data reveal that substantial local gene duplications took place shortly after the whole-genome duplication event. Many of the identified paralog pairs have either diverged in function or become noncoding. Future functional genomics studies will reveal to what extent this rich source of divergence in genetic sequence is likely to have facilitated the evolution of extreme phenotypic plasticity required for an anadromous life-cycle.

  10. Distinct Defects in Spine Formation or Pruning in Two Gene Duplication Mouse Models of Autism.

    Science.gov (United States)

    Wang, Miao; Li, Huiping; Takumi, Toru; Qiu, Zilong; Xu, Xiu; Yu, Xiang; Bian, Wen-Jie

    2017-04-01

    Autism spectrum disorder (ASD) encompasses a complex set of developmental neurological disorders, characterized by deficits in social communication and excessive repetitive behaviors. In recent years, ASD is increasingly being considered as a disease of the synapse. One main type of genetic aberration leading to ASD is gene duplication, and several mouse models have been generated mimicking these mutations. Here, we studied the effects of MECP2 duplication and human chromosome 15q11-13 duplication on synaptic development and neural circuit wiring in the mouse sensory cortices. We showed that mice carrying MECP2 duplication had specific defects in spine pruning, while the 15q11-13 duplication mouse model had impaired spine formation. Our results demonstrate that spine pathology varies significantly between autism models and that distinct aspects of neural circuit development may be targeted in different ASD mutations. Our results further underscore the importance of gene dosage in normal development and function of the brain.

  11. Gene duplication and divergence of long wavelength-sensitive opsin genes in the guppy, Poecilia reticulata.

    Science.gov (United States)

    Watson, Corey T; Gray, Suzanne M; Hoffmann, Margarete; Lubieniecki, Krzysztof P; Joy, Jeffrey B; Sandkam, Ben A; Weigel, Detlef; Loew, Ellis; Dreyer, Christine; Davidson, William S; Breden, Felix

    2011-02-01

    Female preference for male orange coloration in the genus Poecilia suggests a role for duplicated long wavelength-sensitive (LWS) opsin genes in facilitating behaviors related to mate choice in these species. Previous work has shown that LWS gene duplication in this genus has resulted in expansion of long wavelength visual capacity as determined by microspectrophotometry (MSP). However, the relationship between LWS genomic repertoires and expression of LWS retinal cone classes within a given species is unclear. Our previous study in the related species, Xiphophorus helleri, was the first characterization of the complete LWS opsin genomic repertoire in conjunction with MSP expression data in the family Poeciliidae, and revealed the presence of four LWS loci and two distinct LWS cone classes. In this study we characterized the genomic organization of LWS opsin genes by BAC clone sequencing, and described the full range of cone cell types in the retina of the colorful Cumaná guppy, Poecilia reticulata. In contrast to X. helleri, MSP data from the Cumaná guppy revealed three LWS cone classes. Comparisons of LWS genomic organization described here for Cumaná to that of X. helleri indicate that gene divergence and not duplication was responsible for the evolution of a novel LWS haplotype in the Cumaná guppy. This lineage-specific divergence is likely responsible for a third additional retinal cone class not present in X. helleri, and may have facilitated the strong sexual selection driven by female preference for orange color patterns associated with the genus Poecilia.

  12. Methods for identifying and mapping recent segmental and gene duplications in eukaryotic genomes.

    Science.gov (United States)

    Khaja, Razi; MacDonald, Jeffrey R; Zhang, Junjun; Scherer, Stephen W

    2006-01-01

    The aim of this chapter is to provide instruction for analyzing and mapping recent segmental and gene duplications in eukaryotic genomes. We describe a bioinformatics-based approach utilizing computational tools to manage eukaryotic genome sequences to characterize and understand the evolutionary fates and trajectories of duplicated genes. An introduction to bioinformatics tools and programs such as BLAST, Perl, BioPerl, and the GFF specification provides the necessary background to complete this analysis for any eukaryotic genome of interest.

  13. Dynamics of gene duplication in the genomes of chlorophyll d-producing cyanobacteria: implications for the ecological niche.

    Science.gov (United States)

    Miller, Scott R; Wood, A Michelle; Blankenship, Robert E; Kim, Maria; Ferriera, Steven

    2011-01-01

    Gene duplication may be an important mechanism for the evolution of new functions and for the adaptive modulation of gene expression via dosage effects. Here, we analyzed the fate of gene duplicates for two strains of a novel group of cyanobacteria (genus Acaryochloris) that produces the far-red light absorbing chlorophyll d as its main photosynthetic pigment. The genomes of both strains contain an unusually high number of gene duplicates for bacteria. As has been observed for eukaryotic genomes, we find that the demography of gene duplicates can be well modeled by a birth-death process. Most duplicated Acaryochloris genes are of comparatively recent origin, are strain-specific, and tend to be located on different genetic elements. Analyses of selection on duplicates of different divergence classes suggest that a minority of paralogs exhibit near neutral evolutionary dynamics immediately following duplication but that most duplicate pairs (including those which have been retained for long periods) are under strong purifying selection against amino acid change. The likelihood of duplicate retention varied among gene functional classes, and the pronounced differences between strains in the pool of retained recent duplicates likely reflects differences in the nutrient status and other characteristics of their respective environments. We conclude that most duplicates are quickly purged from Acaryochloris genomes and that those which are retained likely make important contributions to organism ecology by conferring fitness benefits via gene dosage effects. The mechanism of enhanced duplication may involve homologous recombination between genetic elements mediated by paralogous copies of recA.

  14. Divergence of recently duplicated M{gamma}-type MADS-box genes in Petunia.

    Science.gov (United States)

    Bemer, Marian; Gordon, Jonathan; Weterings, Koen; Angenent, Gerco C

    2010-02-01

    The MADS-box transcription factor family has expanded considerably in plants via gene and genome duplications and can be subdivided into type I and MIKC-type genes. The two gene classes show a different evolutionary history. Whereas the MIKC-type genes originated during ancient genome duplications, as well as during more recent events, the type I loci appear to experience high turnover with many recent duplications. This different mode of origin also suggests a different fate for the type I duplicates, which are thought to have a higher chance to become silenced or lost from the genome. To get more insight into the evolution of the type I MADS-box genes, we isolated nine type I genes from Petunia, which belong to the Mgamma subclass, and investigated the divergence of their coding and regulatory regions. The isolated genes could be subdivided into two categories: two genes were highly similar to Arabidopsis Mgamma-type genes, whereas the other seven genes showed less similarity to Arabidopsis genes and originated more recently. Two of the recently duplicated genes were found to contain deleterious mutations in their coding regions, and expression analysis revealed that a third paralog was silenced by mutations in its regulatory region. However, in addition to the three genes that were subjected to nonfunctionalization, we also found evidence for neofunctionalization of one of the Petunia Mgamma-type genes. Our study shows a rapid divergence of recently duplicated Mgamma-type MADS-box genes and suggests that redundancy among type I paralogs may be less common than expected.

  15. Restriction and recruitment-gene duplication and the origin and evolution of snake venom toxins.

    Science.gov (United States)

    Hargreaves, Adam D; Swain, Martin T; Hegarty, Matthew J; Logan, Darren W; Mulley, John F

    2014-08-01

    Snake venom has been hypothesized to have originated and diversified through a process that involves duplication of genes encoding body proteins with subsequent recruitment of the copy to the venom gland, where natural selection acts to develop or increase toxicity. However, gene duplication is known to be a rare event in vertebrate genomes, and the recruitment of duplicated genes to a novel expression domain (neofunctionalization) is an even rarer process that requires the evolution of novel combinations of transcription factor binding sites in upstream regulatory regions. Therefore, although this hypothesis concerning the evolution of snake venom is very unlikely and should be regarded with caution, it is nonetheless often assumed to be established fact, hindering research into the true origins of snake venom toxins. To critically evaluate this hypothesis, we have generated transcriptomic data for body tissues and salivary and venom glands from five species of venomous and nonvenomous reptiles. Our comparative transcriptomic analysis of these data reveals that snake venom does not evolve through the hypothesized process of duplication and recruitment of genes encoding body proteins. Indeed, our results show that many proposed venom toxins are in fact expressed in a wide variety of body tissues, including the salivary gland of nonvenomous reptiles and that these genes have therefore been restricted to the venom gland following duplication, not recruited. Thus, snake venom evolves through the duplication and subfunctionalization of genes encoding existing salivary proteins. These results highlight the danger of the elegant and intuitive "just-so story" in evolutionary biology.

  16. Subfunctionalization reduces the fitness cost of gene duplication in humans by buffering dosage imbalances

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    Fernández Ariel

    2011-12-01

    Full Text Available Abstract Background Driven essentially by random genetic drift, subfunctionalization has been identified as a possible non-adaptive mechanism for the retention of duplicate genes in small-population species, where widespread deleterious mutations are likely to cause complementary loss of subfunctions across gene copies. Through subfunctionalization, duplicates become indispensable to maintain the functional requirements of the ancestral locus. Yet, gene duplication produces a dosage imbalance in the encoded proteins and thus, as investigated in this paper, subfunctionalization must be subject to the selective forces arising from the fitness bottleneck introduced by the duplication event. Results We show that, while arising from random drift, subfunctionalization must be inescapably subject to selective forces, since the diversification of expression patterns across paralogs mitigates duplication-related dosage imbalances in the concentrations of encoded proteins. Dosage imbalance effects become paramount when proteins rely on obligatory associations to maintain their structural integrity, and are expected to be weaker when protein complexation is ephemeral or adventitious. To establish the buffering effect of subfunctionalization on selection pressure, we determine the packing quality of encoded proteins, an established indicator of dosage sensitivity, and correlate this parameter with the extent of paralog segregation in humans, using species with larger population -and more efficient selection- as controls. Conclusions Recognizing the role of subfunctionalization as a dosage-imbalance buffer in gene duplication events enabled us to reconcile its mechanistic nonadaptive origin with its adaptive role as an enabler of the evolution of genetic redundancy. This constructive role was established in this paper by proving the following assertion: If subfunctionalization is indeed adaptive, its effect on paralog segregation should scale with the dosage

  17. Detecting functional divergence after gene duplication through evolutionary changes in posttranslational regulatory sequences.

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    Nguyen Ba, Alex N; Strome, Bob; Hua, Jun Jie; Desmond, Jonathan; Gagnon-Arsenault, Isabelle; Weiss, Eric L; Landry, Christian R; Moses, Alan M

    2014-12-01

    Gene duplication is an important evolutionary mechanism that can result in functional divergence in paralogs due to neo-functionalization or sub-functionalization. Consistent with functional divergence after gene duplication, recent studies have shown accelerated evolution in retained paralogs. However, little is known in general about the impact of this accelerated evolution on the molecular functions of retained paralogs. For example, do new functions typically involve changes in enzymatic activities, or changes in protein regulation? Here we study the evolution of posttranslational regulation by examining the evolution of important regulatory sequences (short linear motifs) in retained duplicates created by the whole-genome duplication in budding yeast. To do so, we identified short linear motifs whose evolutionary constraint has relaxed after gene duplication with a likelihood-ratio test that can account for heterogeneity in the evolutionary process by using a non-central chi-squared null distribution. We find that short linear motifs are more likely to show changes in evolutionary constraints in retained duplicates compared to single-copy genes. We examine changes in constraints on known regulatory sequences and show that for the Rck1/Rck2, Fkh1/Fkh2, Ace2/Swi5 paralogs, they are associated with previously characterized differences in posttranslational regulation. Finally, we experimentally confirm our prediction that for the Ace2/Swi5 paralogs, Cbk1 regulated localization was lost along the lineage leading to SWI5 after gene duplication. Our analysis suggests that changes in posttranslational regulation mediated by short regulatory motifs systematically contribute to functional divergence after gene duplication.

  18. Temporal pattern of loss/persistence of duplicate genes involved in signal transduction and metabolic pathways after teleost-specific genome duplication

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    Sato Yukuto

    2009-06-01

    Full Text Available Abstract Background Recent genomic studies have revealed a teleost-specific third-round whole genome duplication (3R-WGD event occurred in a common ancestor of teleost fishes. However, it is unclear how the genes duplicated in this event were lost or persisted during the diversification of teleosts, and therefore, how many of the duplicated genes contribute to the genetic differences among teleosts. This subject is also important for understanding the process of vertebrate evolution through WGD events. We applied a comparative evolutionary approach to this question by focusing on the genes involved in long-term potentiation, taste and olfactory transduction, and the tricarboxylic acid cycle, based on the whole genome sequences of four teleosts; zebrafish, medaka, stickleback, and green spotted puffer fish. Results We applied a state-of-the-art method of maximum-likelihood phylogenetic inference and conserved synteny analyses to each of 130 genes involved in the above biological systems of human. These analyses identified 116 orthologous gene groups between teleosts and tetrapods, and 45 pairs of 3R-WGD-derived duplicate genes among them. This suggests that more than half [(45×2/(116+45] = 56.5% of the loci, probably more than ten thousand genes, present in a common ancestor of the four teleosts were still duplicated after the 3R-WGD. The estimated temporal pattern of gene loss suggested that, after the 3R-WGD, many (71/116 of the duplicated genes were rapidly lost during the initial 75 million years (MY, whereas on average more than half (27.3/45 of the duplicated genes remaining in the ancestor of the four teleosts (45/116 have persisted for about 275 MY. The 3R-WGD-derived duplicates that have persisted for a long evolutionary periods of time had significantly larger number of interacting partners and longer length of protein coding sequence, implying that they tend to be more multifunctional than the singletons after the 3R-WGD. Conclusion

  19. A young Drosophila duplicate gene plays essential roles in spermatogenesis by regulating several Y-linked male fertility genes.

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    Yun Ding

    Full Text Available Gene duplication is supposed to be the major source for genetic innovations. However, how a new duplicate gene acquires functions by integrating into a pathway and results in adaptively important phenotypes has remained largely unknown. Here, we investigated the biological roles and the underlying molecular mechanism of the young kep1 gene family in the Drosophila melanogaster species subgroup to understand the origin and evolution of new genes with new functions. Sequence and expression analysis demonstrates that one of the new duplicates, nsr (novel spermatogenesis regulator, exhibits positive selection signals and novel subcellular localization pattern. Targeted mutagenesis and whole-transcriptome sequencing analysis provide evidence that nsr is required for male reproduction associated with sperm individualization, coiling, and structural integrity of the sperm axoneme via regulation of several Y chromosome fertility genes post-transcriptionally. The absence of nsr-like expression pattern and the presence of the corresponding cis-regulatory elements of the parental gene kep1 in the pre-duplication species Drosophila yakuba indicate that kep1 might not be ancestrally required for male functions and that nsr possibly has experienced the neofunctionalization process, facilitated by changes of trans-regulatory repertories. These findings not only present a comprehensive picture about the evolution of a new duplicate gene but also show that recently originated duplicate genes can acquire multiple biological roles and establish novel functional pathways by regulating essential genes.

  20. Trichomonas transmembrane cyclases result from massive gene duplication and concomitant development of pseudogenes.

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    Jike Cui

    2010-08-01

    Full Text Available Trichomonas vaginalis has an unusually large genome (approximately 160 Mb encoding approximately 60,000 proteins. With the goal of beginning to understand why some Trichomonas genes are present in so many copies, we characterized here a family of approximately 123 Trichomonas genes that encode transmembrane adenylyl cyclases (TMACs.The large family of TMACs genes is the result of recent duplications of a small set of ancestral genes that appear to be unique to trichomonads. Duplicated TMAC genes are not closely associated with repetitive elements, and duplications of flanking sequences are rare. However, there is evidence for TMAC gene replacements by homologous recombination. A high percentage of TMAC genes (approximately 46% are pseudogenes, as they contain stop codons and/or frame shifts, or the genes are truncated. Numerous stop codons present in the genome project G3 strain are not present in orthologous genes of two other Trichomonas strains (S1 and B7RC2. Each TMAC is composed of a series of N-terminal transmembrane helices and a single C-terminal cyclase domain that has adenylyl cyclase activity. Multiple TMAC genes are transcribed by Trichomonas cloned by limiting dilution.We conclude that one reason for the unusually large genome of Trichomonas is the presence of unstable families of genes such as those encoding TMACs that are undergoing massive gene duplication and concomitant development of pseudogenes.

  1. Local synteny and codon usage contribute to asymmetric sequence divergence of Saccharomyces cerevisiae gene duplicates

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    Bergthorsson Ulfar

    2011-09-01

    Full Text Available Abstract Background Duplicated genes frequently experience asymmetric rates of sequence evolution. Relaxed selective constraints and positive selection have both been invoked to explain the observation that one paralog within a gene-duplicate pair exhibits an accelerated rate of sequence evolution. In the majority of studies where asymmetric divergence has been established, there is no indication as to which gene copy, ancestral or derived, is evolving more rapidly. In this study we investigated the effect of local synteny (gene-neighborhood conservation and codon usage on the sequence evolution of gene duplicates in the S. cerevisiae genome. We further distinguish the gene duplicates into those that originated from a whole-genome duplication (WGD event (ohnologs versus small-scale duplications (SSD to determine if there exist any differences in their patterns of sequence evolution. Results For SSD pairs, the derived copy evolves faster than the ancestral copy. However, there is no relationship between rate asymmetry and synteny conservation (ancestral-like versus derived-like in ohnologs. mRNA abundance and optimal codon usage as measured by the CAI is lower in the derived SSD copies relative to ancestral paralogs. Moreover, in the case of ohnologs, the faster-evolving copy has lower CAI and lowered expression. Conclusions Together, these results suggest that relaxation of selection for codon usage and gene expression contribute to rate asymmetry in the evolution of duplicated genes and that in SSD pairs, the relaxation of selection stems from the loss of ancestral regulatory information in the derived copy.

  2. Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures

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    Kesterson Robert A

    2003-04-01

    Full Text Available Abstract Background Chromosomal abnormalities affecting human chromosome 15q11-q13 underlie multiple genomic disorders caused by deletion, duplication and triplication of intervals in this region. These events are mediated by highly homologous segments of DNA, or duplicons, that facilitate mispairing and unequal cross-over in meiosis. The gene encoding an amyloid precursor protein-binding protein (APBA2 was previously mapped to the distal portion of the interval commonly deleted in Prader-Willi and Angelman syndromes and duplicated in cases of autism. Results We show that this gene actually maps to a more telomeric location and is partially duplicated within the broader region. Two highly homologous copies of an interval containing a large 5' exon and downstream sequence are located ~5 Mb distal to the intact locus. The duplicated copies, containing the first coding exon of APBA2, can be distinguished by single nucleotide sequence differences and are transcriptionally inactive. Adjacent to APBA2 maps a gene termed KIAA0574. The protein encoded by this gene is weakly homologous to a protein termed X123 that in turn maps adjacent to APBA1 on 9q21.12; APBA1 is highly homologous to APBA2 in the C-terminal region and is distinguished from APBA2 by the N-terminal region encoded by this duplicated exon. Conclusion The duplication of APBA2 sequences in this region adds to a complex picture of different low copy repeats present across this region and elsewhere on the chromosome.

  3. Gene Duplication, Population Genomics, and Species-Level Differentiation within a Tropical Mountain Shrub

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    Mastretta-Yanes, Alicia; Zamudio, Sergio; Jorgensen, Tove H.; Arrigo, Nils; Alvarez, Nadir; Piñero, Daniel; Emerson, Brent C.

    2014-01-01

    Gene duplication leads to paralogy, which complicates the de novo assembly of genotyping-by-sequencing (GBS) data. The issue of paralogous genes is exacerbated in plants, because they are particularly prone to gene duplication events. Paralogs are normally filtered from GBS data before undertaking population genomics or phylogenetic analyses. However, gene duplication plays an important role in the functional diversification of genes and it can also lead to the formation of postzygotic barriers. Using populations and closely related species of a tropical mountain shrub, we examine 1) the genomic differentiation produced by putative orthologs, and 2) the distribution of recent gene duplication among lineages and geography. We find high differentiation among populations from isolated mountain peaks and species-level differentiation within what is morphologically described as a single species. The inferred distribution of paralogs among populations is congruent with taxonomy and shows that GBS could be used to examine recent gene duplication as a source of genomic differentiation of nonmodel species. PMID:25223767

  4. Evolution dynamics of a model for gene duplication under adaptive conflict

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    Ancliff, Mark; Park, Jeong-Man

    2014-06-01

    We present and solve the dynamics of a model for gene duplication showing escape from adaptive conflict. We use a Crow-Kimura quasispecies model of evolution where the fitness landscape is a function of Hamming distances from two reference sequences, which are assumed to optimize two different gene functions, to describe the dynamics of a mixed population of individuals with single and double copies of a pleiotropic gene. The evolution equations are solved through a spin coherent state path integral, and we find two phases: one is an escape from an adaptive conflict phase, where each copy of a duplicated gene evolves toward subfunctionalization, and the other is a duplication loss of function phase, where one copy maintains its pleiotropic form and the other copy undergoes neutral mutation. The phase is determined by a competition between the fitness benefits of subfunctionalization and the greater mutational load associated with maintaining two gene copies. In the escape phase, we find a dynamics of an initial population of single gene sequences only which escape adaptive conflict through gene duplication and find that there are two time regimes: until a time t* single gene sequences dominate, and after t* double gene sequences outgrow single gene sequences. The time t* is identified as the time necessary for subfunctionalization to evolve and spread throughout the double gene sequences, and we show that there is an optimum mutation rate which minimizes this time scale.

  5. A critical assessment of cross-species detection of gene duplicates using comparative genomic hybridization

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    Renn Suzy CP

    2010-05-01

    Full Text Available Abstract Background Comparison of genomic DNA among closely related strains or species is a powerful approach for identifying variation in evolutionary processes. One potent source of genomic variation is gene duplication, which is prevalent among individuals and species. Array comparative genomic hybridization (aCGH has been successfully utilized to detect this variation among lineages. Here, beyond the demonstration that gene duplicates among species can be quantified with aCGH, we consider the effect of sequence divergence on the ability to detect gene duplicates. Results Using the X chromosome genomic content difference between male D. melanogaster and female D. yakuba and D. simulans, we describe a decrease in the ability to accurately measure genomic content (copy number for orthologs that are only 90% identical. We demonstrate that genome characteristics (e.g. chromatin environment and non-orthologous sequence similarity can also affect the ability to accurately measure genomic content. We describe a normalization strategy and statistical criteria to be used for the identification of gene duplicates among any species group for which an array platform is available from a closely related species. Conclusions Array CGH can be used to effectively identify gene duplication and genome content; however, certain biases are present due to sequence divergence and other genome characteristics resulting from the divergence between lineages. Highly conserved gene duplicates will be more readily recovered by aCGH. Duplicates that have been retained for a selective advantage due to directional selection acting on many loci in one or both gene copies are likely to be under-represented. The results of this study should inform the interpretation of both previously published and future work that employs this powerful technique.

  6. Comparative Evolution of Duplicated Ddx3 Genes in Teleosts: Insights from Japanese Flounder, Paralichthys olivaceus.

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    Wang, Zhongkai; Liu, Wei; Song, Huayu; Wang, Huizhen; Liu, Jinxiang; Zhao, Haitao; Du, Xinxin; Zhang, Quanqi

    2015-06-24

    Following the two rounds of whole-genome duplication that occurred during deuterostome evolution, a third genome duplication event occurred in the stem lineage of ray-finned fishes. This teleost-specific genome duplication is thought to be responsible for the biological diversification of ray-finned fishes. DEAD-box polypeptide 3 (DDX3) belongs to the DEAD-box RNA helicase family. Although their functions in humans have been well studied, limited information is available regarding their function in teleosts. In this study, two teleost Ddx3 genes were first identified in the transcriptome of Japanese flounder (Paralichthys olivaceus). We confirmed that the two genes originated from teleost-specific genome duplication through synteny and phylogenetic analysis. Additionally, comparative analysis of genome structure, molecular evolution rate, and expression pattern of the two genes in Japanese flounder revealed evidence of subfunctionalization of the duplicated Ddx3 genes in teleosts. Thus, the results of this study reveal novel insights into the evolution of the teleost Ddx3 genes and constitute important groundwork for further research on this gene family.

  7. Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio: evidence for subfunctionalization or neofunctionalization of duplicated genes

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    Denovan-Wright Eileen M

    2009-09-01

    Full Text Available Abstract Background In the Duplication-Degeneration-Complementation (DDC model, subfunctionalization and neofunctionalization have been proposed as important processes driving the retention of duplicated genes in the genome. These processes are thought to occur by gain or loss of regulatory elements in the promoters of duplicated genes. We tested the DDC model by determining the transcriptional induction of fatty acid-binding proteins (Fabps genes by dietary fatty acids (FAs in zebrafish. We chose zebrafish for this study for two reasons: extensive bioinformatics resources are available for zebrafish at zfin.org and zebrafish contains many duplicated genes owing to a whole genome duplication event that occurred early in the ray-finned fish lineage approximately 230-400 million years ago. Adult zebrafish were fed diets containing either fish oil (12% lipid, rich in highly unsaturated fatty acid, sunflower oil (12% lipid, rich in linoleic acid, linseed oil (12% lipid, rich in linolenic acid, or low fat (4% lipid, low fat diet for 10 weeks. FA profiles and the steady-state levels of fabp mRNA and heterogeneous nuclear RNA in intestine, liver, muscle and brain of zebrafish were determined. Result FA profiles assayed by gas chromatography differed in the intestine, brain, muscle and liver depending on diet. The steady-state level of mRNA for three sets of duplicated genes, fabp1a/fabp1b.1/fabp1b.2, fabp7a/fabp7b, and fabp11a/fabp11b, was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR. In brain, the steady-state level of fabp7b mRNAs was induced in fish fed the linoleic acid-rich diet; in intestine, the transcript level of fabp1b.1 and fabp7b were elevated in fish fed the linolenic acid-rich diet; in liver, the level of fabp7a mRNAs was elevated in fish fed the low fat diet; and in muscle, the level of fabp7a and fabp11a mRNAs were elevated in fish fed the linolenic acid-rich or the low fat diets. In all cases

  8. Molecular evolution of the duplicated TFIIAγ genes in Oryzeae and its relatives

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    Sun Hong-Zheng

    2010-05-01

    Full Text Available Abstract Background Gene duplication provides raw genetic materials for evolutionary novelty and adaptation. The evolutionary fate of duplicated transcription factor genes is less studied although transcription factor gene plays important roles in many biological processes. TFIIAγ is a small subunit of TFIIA that is one of general transcription factors required by RNA polymerase II. Previous studies identified two TFIIAγ-like genes in rice genome and found that these genes either conferred resistance to rice bacterial blight or could be induced by pathogen invasion, raising the question as to their functional divergence and evolutionary fates after gene duplication. Results We reconstructed the evolutionary history of the TFIIAγ genes from main lineages of angiosperms and demonstrated that two TFIIAγ genes (TFIIAγ1 and TFIIAγ5 arose from a whole genome duplication that happened in the common ancestor of grasses. Likelihood-based analyses with branch, codon, and branch-site models showed no evidence of positive selection but a signature of relaxed selective constraint after the TFIIAγ duplication. In particular, we found that the nonsynonymous/synonymous rate ratio (ω = dN/dS of the TFIIAγ1 sequences was two times higher than that of TFIIAγ5 sequences, indicating highly asymmetric rates of protein evolution in rice tribe and its relatives, with an accelerated rate of TFIIAγ1 gene. Our expression data and EST database search further indicated that after whole genome duplication, the expression of TFIIAγ1 gene was significantly reduced while TFIIAγ5 remained constitutively expressed and maintained the ancestral role as a subunit of the TFIIA complex. Conclusion The evolutionary fate of TFIIAγ duplicates is not consistent with the neofunctionalization model that predicts that one of the duplicated genes acquires a new function because of positive Darwinian selection. Instead, we suggest that subfunctionalization might be involved in

  9. Dating and functional characterization of duplicated genes in the apple (Malus domestica Borkh. by analyzing EST data

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    Sanzol Javier

    2010-05-01

    Full Text Available Abstract Background Gene duplication is central to genome evolution. In plants, genes can be duplicated through small-scale events and large-scale duplications often involving polyploidy. The apple belongs to the subtribe Pyrinae (Rosaceae, a diverse lineage that originated via allopolyploidization. Both small-scale duplications and polyploidy may have been important mechanisms shaping the genome of this species. Results This study evaluates the gene duplication and polyploidy history of the apple by characterizing duplicated genes in this species using EST data. Overall, 68% of the apple genes were clustered into families with a mean copy-number of 4.6. Analysis of the age distribution of gene duplications supported a continuous mode of small-scale duplications, plus two episodes of large-scale duplicates of vastly different ages. The youngest was consistent with the polyploid origin of the Pyrinae 37-48 MYBP, whereas the older may be related to γ-triplication; an ancient hexapolyploidization previously characterized in the four sequenced eurosid genomes and basal to the eurosid-asterid divergence. Duplicated genes were studied for functional diversification with an emphasis on young paralogs; those originated during or after the formation of the Pyrinae lineage. Unequal assignment of single-copy genes and gene families to Gene Ontology categories suggested functional bias in the pattern of gene retention of paralogs. Young paralogs related to signal transduction, metabolism, and energy pathways have been preferentially retained. Non-random retention of duplicated genes seems to have mediated the expansion of gene families, some of which may have substantially increased their members after the origin of the Pyrinae. The joint analysis of over-duplicated functional categories and phylogenies, allowed evaluation of the role of both polyploidy and small-scale duplications during this process. Finally, gene expression analysis indicated that 82

  10. Molecular evolution accompanying functional divergence of duplicated genes along the plant starch biosynthesis pathway.

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    Nougué, Odrade; Corbi, Jonathan; Ball, Steven G; Manicacci, Domenica; Tenaillon, Maud I

    2014-05-15

    Starch is the main source of carbon storage in the Archaeplastida. The starch biosynthesis pathway (sbp) emerged from cytosolic glycogen metabolism shortly after plastid endosymbiosis and was redirected to the plastid stroma during the green lineage divergence. The SBP is a complex network of genes, most of which are members of large multigene families. While some gene duplications occurred in the Archaeplastida ancestor, most were generated during the sbp redirection process, and the remaining few paralogs were generated through compartmentalization or tissue specialization during the evolution of the land plants. In the present study, we tested models of duplicated gene evolution in order to understand the evolutionary forces that have led to the development of SBP in angiosperms. We combined phylogenetic analyses and tests on the rates of evolution along branches emerging from major duplication events in six gene families encoding sbp enzymes. We found evidence of positive selection along branches following cytosolic or plastidial specialization in two starch phosphorylases and identified numerous residues that exhibited changes in volume, polarity or charge. Starch synthases, branching and debranching enzymes functional specializations were also accompanied by accelerated evolution. However, none of the sites targeted by selection corresponded to known functional domains, catalytic or regulatory. Interestingly, among the 13 duplications tested, 7 exhibited evidence of positive selection in both branches emerging from the duplication, 2 in only one branch, and 4 in none of the branches. The majority of duplications were followed by accelerated evolution targeting specific residues along both branches. This pattern was consistent with the optimization of the two sub-functions originally fulfilled by the ancestral gene before duplication. Our results thereby provide strong support to the so-called "Escape from Adaptive Conflict" (EAC) model. Because none of the

  11. Functional divergence of gene duplicates – a domain-centric view

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    Khaladkar Mugdha

    2012-07-01

    Full Text Available Abstract Background Gene duplicates have been shown to evolve at different rates. Here we further investigate the mechanism and functional underpinning of this phenomenon by assessing asymmetric evolution specifically within functional domains of gene duplicates. Results Based on duplicate genes in five teleost fishes resulting from a whole genome duplication event, we first show that a Fisher Exact test based approach to detect asymmetry is more sensitive than the previously used Likelihood Ratio test. Using our Fisher Exact test, we found that the evolutionary rate asymmetry in the overall protein is largely explained by the asymmetric evolution within specific protein domains. Moreover, among cases of asymmetrically evolving domains, for the gene copy containing a fast evolving domain, the non-synonymous substitutions often cluster within the fast evolving domain. We found that rare substitutions were preferred within asymmetrically evolving domains suggestive of functional divergence. While overall ~32 % of the domains tested were found to be evolving asymmetrically, certain protein domains such as the Tyrosine and Ser/Thr Kinase domains had a much greater prevalence of asymmetric evolution. Finally, based on the spatial expression of Zebra fish duplicate proteins during development, we found that protein pairs containing asymmetrically evolving domains had a greater divergence in gene expression as compared to the duplicate proteins that did not exhibit asymmetric evolution. Conclusions Taken together, our results suggest that the previously observed asymmetry in the overall duplicate protein evolution is largely due to divergence of specific domains of the protein, and coincides with divergence in spatial expression domains.

  12. Partial duplications of the ATRX gene cause the ATR-X syndrome.

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    Thienpont, Bernard; de Ravel, Thomy; Van Esch, Hilde; Van Schoubroeck, Dominique; Moerman, Philippe; Vermeesch, Joris Robert; Fryns, Jean-Pierre; Froyen, Guy; Lacoste, Caroline; Badens, Catherine; Devriendt, Koen

    2007-10-01

    ATR-X syndrome is a rare syndromic X-linked mental retardation disorder. We report that some of the patients suspected of ATR-X carry large intragenic duplications in the ATRX gene, leading to an absence of ATRX mRNA and of the protein. These findings underscore the need for including quantitative analyses to mutation analysis of the ATRX gene.

  13. Compensatory Drift and the Evolutionary Dynamics of Dosage-Sensitive Duplicate Genes.

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    Thompson, Ammon; Zakon, Harold H; Kirkpatrick, Mark

    2016-02-01

    Dosage-balance selection preserves functionally redundant duplicates (paralogs) at the optimum for their combined expression. Here we present a model of the dynamics of duplicate genes coevolving under dosage-balance selection. We call this the compensatory drift model. Results show that even when strong dosage-balance selection constrains total expression to the optimum, expression of each duplicate can diverge by drift from its original level. The rate of divergence slows as the strength of stabilizing selection, the size of the mutation effect, and/or the size of the population increases. We show that dosage-balance selection impedes neofunctionalization early after duplication but can later facilitate it. We fit this model to data from sodium channel duplicates in 10 families of teleost fish; these include two convergent lineages of electric fish in which one of the duplicates neofunctionalized. Using the model, we estimated the strength of dosage-balance selection for these genes. The results indicate that functionally redundant paralogs still may undergo radical functional changes after a prolonged period of compensatory drift.

  14. Genomic analysis reveals extensive gene duplication within the bovine TRB locus

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    Law Andy

    2009-04-01

    Full Text Available Abstract Background Diverse TR and IG repertoires are generated by V(DJ somatic recombination. Genomic studies have been pivotal in cataloguing the V, D, J and C genes present in the various TR/IG loci and describing how duplication events have expanded the number of these genes. Such studies have also provided insights into the evolution of these loci and the complex mechanisms that regulate TR/IG expression. In this study we analyze the sequence of the third bovine genome assembly to characterize the germline repertoire of bovine TRB genes and compare the organization, evolution and regulatory structure of the bovine TRB locus with that of humans and mice. Results The TRB locus in the third bovine genome assembly is distributed over 5 scaffolds, extending to ~730 Kb. The available sequence contains 134 TRBV genes, assigned to 24 subgroups, and 3 clusters of DJC genes, each comprising a single TRBD gene, 5–7 TRBJ genes and a single TRBC gene. Seventy-nine of the TRBV genes are predicted to be functional. Comparison with the human and murine TRB loci shows that the gene order, as well as the sequences of non-coding elements that regulate TRB expression, are highly conserved in the bovine. Dot-plot analyses demonstrate that expansion of the genomic TRBV repertoire has occurred via a complex and extensive series of duplications, predominantly involving DNA blocks containing multiple genes. These duplication events have resulted in massive expansion of several TRBV subgroups, most notably TRBV6, 9 and 21 which contain 40, 35 and 16 members respectively. Similarly, duplication has lead to the generation of a third DJC cluster. Analyses of cDNA data confirms the diversity of the TRBV genes and, in addition, identifies a substantial number of TRBV genes, predominantly from the larger subgroups, which are still absent from the genome assembly. The observed gene duplication within the bovine TRB locus has created a repertoire of phylogenetically

  15. On the Complexity of Duplication-Transfer-Loss Reconciliation with Non-Binary Gene Trees.

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    Kordi, Misagh; Bansal, Mukul

    2015-12-23

    Duplication-Transfer-Loss (DTL) reconciliation has emerged as a powerful technique for studying gene family evolution in the presence of horizontal gene transfer. DTL reconciliation takes as input a gene family phylogeny and the corresponding species phylogeny, and reconciles the two by postulating speciation, gene duplication, horizontal gene transfer, and gene loss events. Efficient algorithms exist for finding optimal DTL reconciliations when the gene tree is binary. However, gene trees are frequently non-binary. With such non-binary gene trees, the reconciliation problem seeks to find a binary resolution of the gene tree that minimizes the reconciliation cost. Given the prevalence of non-binary gene trees, many efficient algorithms have been developed for this problem in the context of the simpler Duplication-Loss (DL) reconciliation model. Yet, no efficient algorithms exist for DTL reconciliation with non-binary gene trees and the complexity of the problem remains unknown. In this work, we resolve this open question by showing that the problem is, in fact, NP-hard. Our reduction applies to both the dated and undated formulations of DTL reconciliation. By resolving this long-standing open problem, this work will spur the development of both exact and heuristic algorithms for this important problem.

  16. Evidence of duplicated Hox genes in the most recent common ancestor of extant scorpions.

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    Sharma, Prashant P; Santiago, Marc A; González-Santillán, Edmundo; Monod, Lionel; Wheeler, Ward C

    2015-01-01

    Scorpions (order Scorpiones) are unusual among arthropods, both for the extreme heteronomy of their bauplan and for the high gene family turnover exhibited in their genomes. These phenomena appear to be correlated, as two scorpion species have been shown to possess nearly twice the number of Hox genes present in most arthropods. Segmentally offset anterior expression boundaries of a subset of Hox paralogs have been shown to correspond to transitions in segmental identities in the scorpion posterior tagmata, suggesting that posterior heteronomy in scorpions may have been achieved by neofunctionalization of Hox paralogs. However, both the first scorpion genome sequenced and the developmental genetic data are based on exemplars of Buthidae, one of 19 families of scorpions. It is therefore not known whether Hox paralogy is limited to Buthidae or widespread among scorpions. We surveyed 24 high throughput transcriptomes and the single whole genome available for scorpions, in order to test the prediction that Hox gene duplications are common to the order. We used gene tree parsimony to infer whether the paralogy was consistent with a duplication event in the scorpion common ancestor. Here we show that duplicated Hox genes in non-buthid scorpions occur in six of the ten Hox classes. Gene tree topologies and parsimony-based reconciliation of the gene trees are consistent with a duplication event in the most recent common ancestor of scorpions. These results suggest that a Hox paralogy, and by extension the model of posterior patterning established in a buthid, can be extended to non-Buthidae scorpions.

  17. Duplication and relocation of the functional DPY19L2 gene within low copy repeats

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    Cheung Joseph

    2006-03-01

    Full Text Available Abstract Background Low copy repeats (LCRs are thought to play an important role in recent gene evolution, especially when they facilitate gene duplications. Duplicate genes are fundamental to adaptive evolution, providing substrates for the development of new or shared gene functions. Moreover, silencing of duplicate genes can have an indirect effect on adaptive evolution by causing genomic relocation of functional genes. These changes are theorized to have been a major factor in speciation. Results Here we present a novel example showing functional gene relocation within a LCR. We characterize the genomic structure and gene content of eight related LCRs on human Chromosomes 7 and 12. Two members of a novel transmembrane gene family, DPY19L, were identified in these regions, along with six transcribed pseudogenes. One of these genes, DPY19L2, is found on Chromosome 12 and is not syntenic with its mouse orthologue. Instead, the human locus syntenic to mouse Dpy19l2 contains a pseudogene, DPY19L2P1. This indicates that the ancestral copy of this gene has been silenced, while the descendant copy has remained active. Thus, the functional copy of this gene has been relocated to a new genomic locus. We then describe the expansion and evolution of the DPY19L gene family from a single gene found in invertebrate animals. Ancient duplications have led to multiple homologues in different lineages, with three in fish, frogs and birds and four in mammals. Conclusion Our results show that the DPY19L family has expanded throughout the vertebrate lineage and has undergone recent primate-specific evolution within LCRs.

  18. Duplication and diversification of the hypoxia-inducible IGFBP-1 gene in zebrafish.

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    Hiroyasu Kamei

    Full Text Available BACKGROUND: Gene duplication is the primary force of new gene evolution. Deciphering whether a pair of duplicated genes has evolved divergent functions is often challenging. The zebrafish is uniquely positioned to provide insight into the process of functional gene evolution due to its amenability to genetic and experimental manipulation and because it possess a large number of duplicated genes. METHODOLOGY/PRINCIPAL FINDINGS: We report the identification and characterization of two hypoxia-inducible genes in zebrafish that are co-ortholgs of human IGF binding protein-1 (IGFBP-1. IGFBP-1 is a secreted protein that binds to IGF and modulates IGF actions in somatic growth, development, and aging. Like their human and mouse counterparts, in adult zebrafish igfbp-1a and igfbp-1b are exclusively expressed in the liver. During embryogenesis, the two genes are expressed in overlapping spatial domains but with distinct temporal patterns. While zebrafish IGFBP-1a mRNA was easily detected throughout embryogenesis, IGFBP-1b mRNA was detectable only in advanced stages. Hypoxia induces igfbp-1a expression in early embryogenesis, but induces the igfbp-1b expression later in embryogenesis. Both IGFBP-1a and -b are capable of IGF binding, but IGFBP-1b has much lower affinities for IGF-I and -II because of greater dissociation rates. Overexpression of IGFBP-1a and -1b in zebrafish embryos caused significant decreases in growth and developmental rates. When tested in cultured zebrafish embryonic cells, IGFBP-1a and -1b both inhibited IGF-1-induced cell proliferation but the activity of IGFBP-1b was significantly weaker. CONCLUSIONS/SIGNIFICANCE: These results indicate subfunction partitioning of the duplicated IGFBP-1 genes at the levels of gene expression, physiological regulation, protein structure, and biological actions. The duplicated IGFBP-1 may provide additional flexibility in fine-tuning IGF signaling activities under hypoxia and other catabolic

  19. Gene duplication as a mechanism of genomic adaptation to a changing environment

    Science.gov (United States)

    Kondrashov, Fyodor A.

    2012-01-01

    A subject of extensive study in evolutionary theory has been the issue of how neutral, redundant copies can be maintained in the genome for long periods of time. Concurrently, examples of adaptive gene duplications to various environmental conditions in different species have been described. At this point, it is too early to tell whether or not a substantial fraction of gene copies have initially achieved fixation by positive selection for increased dosage. Nevertheless, enough examples have accumulated in the literature that such a possibility should be considered. Here, I review the recent examples of adaptive gene duplications and make an attempt to draw generalizations on what types of genes may be particularly prone to be selected for under certain environmental conditions. The identification of copy-number variation in ecological field studies of species adapting to stressful or novel environmental conditions may improve our understanding of gene duplications as a mechanism of adaptation and its relevance to the long-term persistence of gene duplications. PMID:22977152

  20. Functional characterization of duplicated Suppressor of Overexpression of Constans 1-like genes in petunia.

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    Jill C Preston

    Full Text Available Flowering time is strictly controlled by a combination of internal and external signals that match seed set with favorable environmental conditions. In the model plant species Arabidopsis thaliana (Brassicaceae, many of the genes underlying development and evolution of flowering have been discovered. However, much remains unknown about how conserved the flowering gene networks are in plants with different growth habits, gene duplication histories, and distributions. Here we functionally characterize three homologs of the flowering gene Suppressor Of Overexpression of Constans 1 (SOC1 in the short-lived perennial Petunia hybrida (petunia, Solanaceae. Similar to A. thaliana soc1 mutants, co-silencing of duplicated petunia SOC1-like genes results in late flowering. This phenotype is most severe when all three SOC1-like genes are silenced. Furthermore, expression levels of the SOC1-like genes Unshaven (UNS and Floral Binding Protein 21 (FBP21, but not FBP28, are positively correlated with developmental age. In contrast to A. thaliana, petunia SOC1-like gene expression did not increase with longer photoperiods, and FBP28 transcripts were actually more abundant under short days. Despite evidence of functional redundancy, differential spatio-temporal expression data suggest that SOC1-like genes might fine-tune petunia flowering in response to photoperiod and developmental stage. This likely resulted from modification of SOC1-like gene regulatory elements following recent duplication, and is a possible mechanism to ensure flowering under both inductive and non-inductive photoperiods.

  1. Early vertebrate chromosome duplications and the evolution of the neuropeptide Y receptor gene regions

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    Brenner Sydney

    2008-06-01

    Full Text Available Abstract Background One of the many gene families that expanded in early vertebrate evolution is the neuropeptide (NPY receptor family of G-protein coupled receptors. Earlier work by our lab suggested that several of the NPY receptor genes found in extant vertebrates resulted from two genome duplications before the origin of jawed vertebrates (gnathostomes and one additional genome duplication in the actinopterygian lineage, based on their location on chromosomes sharing several gene families. In this study we have investigated, in five vertebrate genomes, 45 gene families with members close to the NPY receptor genes in the compact genomes of the teleost fishes Tetraodon nigroviridis and Takifugu rubripes. These correspond to Homo sapiens chromosomes 4, 5, 8 and 10. Results Chromosome regions with conserved synteny were identified and confirmed by phylogenetic analyses in H. sapiens, M. musculus, D. rerio, T. rubripes and T. nigroviridis. 26 gene families, including the NPY receptor genes, (plus 3 described recently by other labs showed a tree topology consistent with duplications in early vertebrate evolution and in the actinopterygian lineage, thereby supporting expansion through block duplications. Eight gene families had complications that precluded analysis (such as short sequence length or variable number of repeated domains and another eight families did not support block duplications (because the paralogs in these families seem to have originated in another time window than the proposed genome duplication events. RT-PCR carried out with several tissues in T. rubripes revealed that all five NPY receptors were expressed in the brain and subtypes Y2, Y4 and Y8 were also expressed in peripheral organs. Conclusion We conclude that the phylogenetic analyses and chromosomal locations of these gene families support duplications of large blocks of genes or even entire chromosomes. Thus, these results are consistent with two early vertebrate

  2. Gene Duplication and Gene Expression Changes Play a Role in the Evolution of Candidate Pollen Feeding Genes in Heliconius Butterflies.

    Science.gov (United States)

    Smith, Gilbert; Macias-Muñoz, Aide; Briscoe, Adriana D

    2016-09-02

    Heliconius possess a unique ability among butterflies to feed on pollen. Pollen feeding significantly extends their lifespan, and is thought to have been important to the diversification of the genus. We used RNA sequencing to examine feeding-related gene expression in the mouthparts of four species of Heliconius and one nonpollen feeding species, Eueides isabella We hypothesized that genes involved in morphology and protein metabolism might be upregulated in Heliconius because they have longer proboscides than Eueides, and because pollen contains more protein than nectar. Using de novo transcriptome assemblies, we tested these hypotheses by comparing gene expression in mouthparts against antennae and legs. We first looked for genes upregulated in mouthparts across all five species and discovered several hundred genes, many of which had functional annotations involving metabolism of proteins (cocoonase), lipids, and carbohydrates. We then looked specifically within Heliconius where we found eleven common upregulated genes with roles in morphology (CPR cuticle proteins), behavior (takeout-like), and metabolism (luciferase-like). Closer examination of these candidates revealed that cocoonase underwent several duplications along the lineage leading to heliconiine butterflies, including two Heliconius-specific duplications. Luciferase-like genes also underwent duplication within lepidopterans, and upregulation in Heliconius mouthparts. Reverse-transcription PCR confirmed that three cocoonases, a peptidase, and one luciferase-like gene are expressed in the proboscis with little to no expression in labial palps and salivary glands. Our results suggest pollen feeding, like other dietary specializations, was likely facilitated by adaptive expansions of preexisting genes-and that the butterfly proboscis is involved in digestive enzyme production.

  3. Zebrafish IGF genes: gene duplication, conservation and divergence, and novel roles in midline and notochord development.

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    Shuming Zou

    Full Text Available Insulin-like growth factors (IGFs are key regulators of development, growth, and longevity. In most vertebrate species including humans, there is one IGF-1 gene and one IGF-2 gene. Here we report the identification and functional characterization of 4 distinct IGF genes (termed as igf-1a, -1b, -2a, and -2b in zebrafish. These genes encode 4 structurally distinct and functional IGF peptides. IGF-1a and IGF-2a mRNAs were detected in multiple tissues in adult fish. IGF-1b mRNA was detected only in the gonad and IGF-2b mRNA only in the liver. Functional analysis showed that all 4 IGFs caused similar developmental defects but with different potencies. Many of these embryos had fully or partially duplicated notochords, suggesting that an excess of IGF signaling causes defects in the midline formation and an expansion of the notochord. IGF-2a, the most potent IGF, was analyzed in depth. IGF-2a expression caused defects in the midline formation and expansion of the notochord but it did not alter the anterior neural patterning. These results not only provide new insights into the functional conservation and divergence of the multiple igf genes but also reveal a novel role of IGF signaling in midline formation and notochord development in a vertebrate model.

  4. A duplicated PLP gene causing Pelizaeus-Merzbacher disease detected by comparative multiplex PCR

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, K.; Sugiyama, N.; Kawanishi, C. [Yokohama City Univ., Yokohama (Japan)] [and others

    1996-07-01

    Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10% - 25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be an important genetic abnormality in PMD and affect myelin formation. 38 ref., 5 figs., 2 tabs.

  5. Preferential duplication of intermodular hub genes: an evolutionary signature in eukaryotes genome networks.

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    Ricardo M Ferreira

    Full Text Available Whole genome protein-protein association networks are not random and their topological properties stem from genome evolution mechanisms. In fact, more connected, but less clustered proteins are related to genes that, in general, present more paralogs as compared to other genes, indicating frequent previous gene duplication episodes. On the other hand, genes related to conserved biological functions present few or no paralogs and yield proteins that are highly connected and clustered. These general network characteristics must have an evolutionary explanation. Considering data from STRING database, we present here experimental evidence that, more than not being scale free, protein degree distributions of organisms present an increased probability for high degree nodes. Furthermore, based on this experimental evidence, we propose a simulation model for genome evolution, where genes in a network are either acquired de novo using a preferential attachment rule, or duplicated with a probability that linearly grows with gene degree and decreases with its clustering coefficient. For the first time a model yields results that simultaneously describe different topological distributions. Also, this model correctly predicts that, to produce protein-protein association networks with number of links and number of nodes in the observed range for Eukaryotes, it is necessary 90% of gene duplication and 10% of de novo gene acquisition. This scenario implies a universal mechanism for genome evolution.

  6. A gene duplication led to specialized gamma-aminobutyrate and beta-alanine aminotransferase in yeast

    DEFF Research Database (Denmark)

    Andersen, Gorm; Andersen, Birgit; Dobritzsch, D.

    2007-01-01

    and related yeasts have two different genes/enzymes to apparently 'distinguish' between the two reactions in a single cell. It is likely that upon duplication similar to 200 million years ago, a specialized Uga1p evolved into a 'novel' transaminase enzyme with broader substrate specificity....

  7. Duplication and Divergence of Floral MADS-Box Genes in Grasses: Evidence for the Generation and Modification of Novel Regulators

    Institute of Scientific and Technical Information of China (English)

    Guixia Xu; Hongzhi Kong

    2007-01-01

    The process of flowering is controlled by a hierarchy of floral genes that act as flowering time genes, inflorescence/floral meristem identity genes, and/or floral organ-identity genes. The most important and well-characterized floral genes are those that belong to the MADS-box family of transcription factors. Compelling evidence suggests that floral MADS-box genes have experienced a few large-scale duplication events. In particular, the pre-core eudicot duplication events have been considered to correlate with the emergence and diversification of core eudicots. Duplication of floral MADS-box genes has also been documented in monocots, particularly in grasses, although a systematic study is lacking. In the present study, by conducting extensive phylogenetic analyses, we identified pre-Poaceae gene duplication events in each of the AP1, PI, AG, AGL11, AGL2/3/4, and AGL9gene lineages. Comparative genomic studies further indicated that some of these duplications actually resulted from the genome doubling event that occurred 66-70 million years ago (MYA). In addition, we found that after gene duplication, exonization (of intron sequences) and pseudoexonization (of exon sequences) have contributed to the divergence of duplicate genes in sequence structure and, possibly, gene function.

  8. Exact Algorithms for Duplication-Transfer-Loss Reconciliation with Non-Binary Gene Trees.

    Science.gov (United States)

    Kordi, Misagh; Bansal, Mukul S

    2017-06-01

    Duplication-Transfer-Loss (DTL) reconciliation is a powerful method for studying gene family evolution in the presence of horizontal gene transfer. DTL reconciliation seeks to reconcile gene trees with species trees by postulating speciation, duplication, transfer, and loss events. Efficient algorithms exist for finding optimal DTL reconciliations when the gene tree is binary. In practice, however, gene trees are often non-binary due to uncertainty in the gene tree topologies, and DTL reconciliation with non-binary gene trees is known to be NP-hard. In this paper, we present the first exact algorithms for DTL reconciliation with non-binary gene trees. Specifically, we (i) show that the DTL reconciliation problem for non-binary gene trees is fixed-parameter tractable in the maximum degree of the gene tree, (ii) present an exponential-time, but in-practice efficient, algorithm to track and enumerate all optimal binary resolutions of a non-binary input gene tree, and (iii) apply our algorithms to a large empirical data set of over 4700 gene trees from 100 species to study the impact of gene tree uncertainty on DTL-reconciliation and to demonstrate the applicability and utility of our algorithms. The new techniques and algorithms introduced in this paper will help biologists avoid incorrect evolutionary inferences caused by gene tree uncertainty.

  9. Species-specific duplications of NBS-encoding genes in Chinese chestnut (Castanea mollissima)

    Science.gov (United States)

    Zhong, Yan; Li, Yingjun; Huang, Kaihui; Cheng, Zong-Ming

    2015-01-01

    The disease resistance (R) genes play an important role in protecting plants from infection by diverse pathogens in the environment. The nucleotide-binding site (NBS)-leucine-rich repeat (LRR) class of genes is one of the largest R gene families. Chinese chestnut (Castanea mollissima) is resistant to Chestnut Blight Disease, but relatively little is known about the resistance mechanism. We identified 519 NBS-encoding genes, including 374 NBS-LRR genes and 145 NBS-only genes. The majority of Ka/Ks were less than 1, suggesting the purifying selection operated during the evolutionary history of NBS-encoding genes. A minority (4/34) of Ka/Ks in non-TIR gene families were greater than 1, showing that some genes were under positive selection pressure. Furthermore, Ks peaked at a range of 0.4 to 0.5, indicating that ancient duplications arose during the evolution. The relationship between Ka/Ks and Ks indicated greater selective pressure on the newer and older genes with the critical value of Ks = 0.4–0.5. Notably, species-specific duplications were detected in NBS-encoding genes. In addition, the group of RPW8-NBS-encoding genes clustered together as an independent clade located at a relatively basal position in the phylogenetic tree. Many cis-acting elements related to plant defense responses were detected in promoters of NBS-encoding genes. PMID:26559332

  10. Duplication, divergence and persistence in the Phytochrome photoreceptor gene family of cottons (Gossypium spp.

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    Abdukarimov Abdusattor

    2010-06-01

    Full Text Available Abstract Background Phytochromes are a family of red/far-red photoreceptors that regulate a number of important developmental traits in cotton (Gossypium spp., including plant architecture, fiber development, and photoperiodic flowering. Little is known about the composition and evolution of the phytochrome gene family in diploid (G. herbaceum, G. raimondii or allotetraploid (G. hirsutum, G. barbadense cotton species. The objective of this study was to obtain a preliminary inventory and molecular-evolutionary characterization of the phytochrome gene family in cotton. Results We used comparative sequence resources to design low-degeneracy PCR primers that amplify genomic sequence tags (GSTs for members of the PHYA, PHYB/D, PHYC and PHYE gene sub-families from A- and D-genome diploid and AD-genome allotetraploid Gossypium species. We identified two paralogous PHYA genes (designated PHYA1 and PHYA2 in diploid cottons, the result of a Malvaceae-specific PHYA gene duplication that occurred approximately 14 million years ago (MYA, before the divergence of the A- and D-genome ancestors. We identified a single gene copy of PHYB, PHYC, and PHYE in diploid cottons. The allotetraploid genomes have largely retained the complete gene complements inherited from both of the diploid genome ancestors, with at least four PHYA genes and two genes encoding PHYB, PHYC and PHYE in the AD-genomes. We did not identify a PHYD gene in any cotton genomes examined. Conclusions Detailed sequence analysis suggests that phytochrome genes retained after duplication by segmental duplication and allopolyploidy appear to be evolving independently under a birth-and-death-process with strong purifying selection. Our study provides a preliminary phytochrome gene inventory that is necessary and sufficient for further characterization of the biological functions of each of the cotton phytochrome genes, and for the development of 'candidate gene' markers that are potentially useful for

  11. Insight into transcription factor gene duplication from Caenorhabditis elegans Promoterome-driven expression patterns

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    Vidal Marc

    2007-01-01

    Full Text Available Abstract Background The C. elegans Promoterome is a powerful resource for revealing the regulatory mechanisms by which transcription is controlled pan-genomically. Transcription factors will form the core of any systems biology model of genome control and therefore the promoter activity of Promoterome inserts for C. elegans transcription factor genes was examined, in vivo, with a reporter gene approach. Results Transgenic C. elegans strains were generated for 366 transcription factor promoter/gfp reporter gene fusions. GFP distributions were determined, and then summarized with reference to developmental stage and cell type. Reliability of these data was demonstrated by comparison to previously described gene product distributions. A detailed consideration of the results for one C. elegans transcription factor gene family, the Six family, comprising ceh-32, ceh-33, ceh-34 and unc-39 illustrates the value of these analyses. The high proportion of Promoterome reporter fusions that drove GFP expression, compared to previous studies, led to the hypothesis that transcription factor genes might be involved in local gene duplication events less frequently than other genes. Comparison of transcription factor genes of C. elegans and Caenorhabditis briggsae was therefore carried out and revealed very few examples of functional gene duplication since the divergence of these species for most, but not all, transcription factor gene families. Conclusion Examining reporter expression patterns for hundreds of promoters informs, and thereby improves, interpretation of this data type. Genes encoding transcription factors involved in intrinsic developmental control processes appear acutely sensitive to changes in gene dosage through local gene duplication, on an evolutionary time scale.

  12. Ancient gene duplication provided a key molecular step for anaerobic growth of Baker's yeast.

    Science.gov (United States)

    Hayashi, Masaya; Schilke, Brenda; Marszalek, Jaroslaw; Williams, Barry; Craig, Elizabeth A

    2011-07-01

    Mitochondria are essential organelles required for a number of key cellular processes. As most mitochondrial proteins are nuclear encoded, their efficient translocation into the organelle is critical. Transport of proteins across the inner membrane is driven by a multicomponent, matrix-localized "import motor," which is based on the activity of the molecular chaperone Hsp70 and a J-protein cochaperone. In Saccharomyces cerevisiae, two paralogous J-proteins, Pam18 and Mdj2, can form the import motor. Both contain transmembrane and matrix domains, with Pam18 having an additional intermembrane space (IMS) domain. Evolutionary analyses revealed that the origin of the IMS domain of S. cerevisiae Pam18 coincides with a gene duplication event that generated the PAM18/MDJ2 gene pair. The duplication event and origin of the Pam18 IMS domain occurred at the relatively ancient divergence of the fungal subphylum Saccharomycotina. The timing of the duplication event also corresponds with a number of additional functional changes related to mitochondrial function and respiration. Physiological and genetic studies revealed that the IMS domain of Pam18 is required for efficient growth under anaerobic conditions, even though it is dispensable when oxygen is present. Thus, the gene duplication was beneficial for growth capacity under particular environmental conditions as well as diversification of the import motor components.

  13. A single enhancer regulating the differential expression of duplicated red-sensitive opsin genes in zebrafish.

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    Taro Tsujimura

    2010-12-01

    Full Text Available A fundamental step in the evolution of the visual system is the gene duplication of visual opsins and differentiation between the duplicates in absorption spectra and expression pattern in the retina. However, our understanding of the mechanism of expression differentiation is far behind that of spectral tuning of opsins. Zebrafish (Danio rerio have two red-sensitive cone opsin genes, LWS-1 and LWS-2. These genes are arrayed in a tail-to-head manner, in this order, and are both expressed in the long member of double cones (LDCs in the retina. Expression of the longer-wave sensitive LWS-1 occurs later in development and is thus confined to the peripheral, especially ventral-nasal region of the adult retina, whereas expression of LWS-2 occurs earlier and is confined to the central region of the adult retina, shifted slightly to the dorsal-temporal region. In this study, we employed a transgenic reporter assay using fluorescent proteins and P1-artificial chromosome (PAC clones encompassing the two genes and identified a 0.6-kb "LWS-activating region" (LAR upstream of LWS-1, which regulates expression of both genes. Under the 2.6-kb flanking upstream region containing the LAR, the expression pattern of LWS-1 was recapitulated by the fluorescent reporter. On the other hand, when LAR was directly conjugated to the LWS-2 upstream region, the reporter was expressed in the LDCs but also across the entire outer nuclear layer. Deletion of LAR from the PAC clones drastically lowered the reporter expression of the two genes. These results suggest that LAR regulates both LWS-1 and LWS-2 by enhancing their expression and that interaction of LAR with the promoters is competitive between the two genes in a developmentally restricted manner. Sharing a regulatory region between duplicated genes could be a general way to facilitate the expression differentiation in duplicated visual opsins.

  14. New Organelles by Gene Duplication in a Biophysical Model of Eukaryote Endomembrane Evolution

    OpenAIRE

    Ramadas, Rohini; Thattai, Mukund

    2013-01-01

    Extant eukaryotic cells have a dynamic traffic network that consists of diverse membrane-bound organelles exchanging matter via vesicles. This endomembrane system arose and diversified during a period characterized by massive expansions of gene families involved in trafficking after the acquisition of a mitochondrial endosymbiont by a prokaryotic host cell >1.8 billion years ago. Here we investigate the mechanistic link between gene duplication and the emergence of new nonendosymbiotic organe...

  15. CTDGFinder: A Novel Homology-Based Algorithm for Identifying Closely Spaced Clusters of Tandemly Duplicated Genes.

    Science.gov (United States)

    Ortiz, Juan F; Rokas, Antonis

    2017-01-01

    Closely spaced clusters of tandemly duplicated genes (CTDGs) contribute to the diversity of many phenotypes, including chemosensation, snake venom, and animal body plans. CTDGs have traditionally been identified subjectively as genomic neighborhoods containing several gene duplicates in close proximity; however, CTDGs are often highly variable with respect to gene number, intergenic distance, and synteny. This lack of formal definition hampers the study of CTDG evolutionary dynamics and the discovery of novel CTDGs in the exponentially growing body of genomic data. To address this gap, we developed a novel homology-based algorithm, CTDGFinder, which formalizes and automates the identification of CTDGs by examining the physical distribution of individual members of families of duplicated genes across chromosomes. Application of CTDGFinder accurately identified CTDGs for many well-known gene clusters (e.g., Hox and beta-globin gene clusters) in the human, mouse and 20 other mammalian genomes. Differences between previously annotated gene clusters and our inferred CTDGs were due to the exclusion of nonhomologs that have historically been considered parts of specific gene clusters, the inclusion or absence of genes between the CTDGs and their corresponding gene clusters, and the splitting of certain gene clusters into distinct CTDGs. Examination of human genes showing tissue-specific enhancement of their expression by CTDGFinder identified members of several well-known gene clusters (e.g., cytochrome P450s and olfactory receptors) and revealed that they were unequally distributed across tissues. By formalizing and automating CTDG identification, CTDGFinder will facilitate understanding of CTDG evolutionary dynamics, their functional implications, and how they are associated with phenotypic diversity. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e

  16. Genomics 4.0 : syntenic gene and genome duplication drives diversification of plant secondary metabolism and innate immunity in flowering plants : advanced pattern analytics in duplicate genomes

    NARCIS (Netherlands)

    Hofberger, J.A.

    2015-01-01

    Genomics 4.0 - Syntenic Gene and Genome Duplication Drives Diversification of Plant Secondary Metabolism and Innate Immunity in Flowering Plants   Johannes A. Hofberger1, 2, 3 1 Biosystematics Group, Wageningen University & Research Center, Droevendaalsesteeg 1, 6708 PB Wageningen, The Neth

  17. Higher primates, but not New World monkeys, have a duplicate set of enhancers flanking their apoC-I genes.

    Science.gov (United States)

    Puppione, Donald L

    2014-09-01

    Previous studies have demonstrated that the apoC-I gene and its pseudogene on human chromosome 19 are flanked by a duplicate set of enhancers. Multienhancers, ME.1 and ME.2, are located upstream from the genes and the hepatic control region enhancers, HCR.1 and HCR.2, are located downstream. The duplication of the enhancers has been thought to have occurred when the apoC-I gene was duplicated during primate evolution. Currently, the only primate data are for the human enhancers. Examining the genome of other primates (great and lesser apes, Old and New World monkeys), it was possible to locate the duplicate set of enhancers in apes and Old World monkeys. However, only a single set was found in New World monkeys. These observations provide additional evidence that the apoC-I gene and the flanking enhancers underwent duplication after the divergence of Old and New World monkeys.

  18. Phylogenomics of the benzoxazinoid biosynthetic pathway of Poaceae: gene duplications and origin of the Bx cluster

    Directory of Open Access Journals (Sweden)

    Dutartre Leslie

    2012-05-01

    Full Text Available Abstract Background The benzoxazinoids 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA and 2,4-dihydroxy-7- methoxy-1,4-benzoxazin-3-one (DIMBOA, are key defense compounds present in major agricultural crops such as maize and wheat. Their biosynthesis involves nine enzymes thought to form a linear pathway leading to the storage of DI(MBOA as glucoside conjugates. Seven of the genes (Bx1-Bx6 and Bx8 form a cluster at the tip of the short arm of maize chromosome 4 that includes four P450 genes (Bx2-5 belonging to the same CYP71C subfamily. The origin of this cluster is unknown. Results We show that the pathway appeared following several duplications of the TSA gene (α-subunit of tryptophan synthase and of a Bx2-like ancestral CYP71C gene and the recruitment of Bx8 before the radiation of Poaceae. The origins of Bx6 and Bx7 remain unclear. We demonstrate that the Bx2-like CYP71C ancestor was not committed to the benzoxazinoid pathway and that after duplications the Bx2-Bx5 genes were under positive selection on a few sites and underwent functional divergence, leading to the current specific biochemical properties of the enzymes. The absence of synteny between available Poaceae genomes involving the Bx gene regions is in contrast with the conserved synteny in the TSA gene region. Conclusions These results demonstrate that rearrangements following duplications of an IGL/TSA gene and of a CYP71C gene probably resulted in the clustering of the new copies (Bx1 and Bx2 at the tip of a chromosome in an ancestor of grasses. Clustering favored cosegregation and tip chromosomal location favored gene rearrangements that allowed the further recruitment of genes to the pathway. These events, a founding event and elongation events, may have been the key to the subsequent evolution of the benzoxazinoid biosynthetic cluster.

  19. Phylogenomics of the benzoxazinoid biosynthetic pathway of Poaceae: gene duplications and origin of the Bx cluster.

    Science.gov (United States)

    Dutartre, Leslie; Hilliou, Frédérique; Feyereisen, René

    2012-05-11

    The benzoxazinoids 2,4-dihydroxy-1,4-benzoxazin-3-one (DIBOA) and 2,4-dihydroxy-7- methoxy-1,4-benzoxazin-3-one (DIMBOA), are key defense compounds present in major agricultural crops such as maize and wheat. Their biosynthesis involves nine enzymes thought to form a linear pathway leading to the storage of DI(M)BOA as glucoside conjugates. Seven of the genes (Bx1-Bx6 and Bx8) form a cluster at the tip of the short arm of maize chromosome 4 that includes four P450 genes (Bx2-5) belonging to the same CYP71C subfamily. The origin of this cluster is unknown. We show that the pathway appeared following several duplications of the TSA gene (α-subunit of tryptophan synthase) and of a Bx2-like ancestral CYP71C gene and the recruitment of Bx8 before the radiation of Poaceae. The origins of Bx6 and Bx7 remain unclear. We demonstrate that the Bx2-like CYP71C ancestor was not committed to the benzoxazinoid pathway and that after duplications the Bx2-Bx5 genes were under positive selection on a few sites and underwent functional divergence, leading to the current specific biochemical properties of the enzymes. The absence of synteny between available Poaceae genomes involving the Bx gene regions is in contrast with the conserved synteny in the TSA gene region. These results demonstrate that rearrangements following duplications of an IGL/TSA gene and of a CYP71C gene probably resulted in the clustering of the new copies (Bx1 and Bx2) at the tip of a chromosome in an ancestor of grasses. Clustering favored cosegregation and tip chromosomal location favored gene rearrangements that allowed the further recruitment of genes to the pathway. These events, a founding event and elongation events, may have been the key to the subsequent evolution of the benzoxazinoid biosynthetic cluster.

  20. Transcriptional rewiring of the sex determining dmrt1 gene duplicate by transposable elements.

    Directory of Open Access Journals (Sweden)

    Amaury Herpin

    2010-02-01

    Full Text Available Control and coordination of eukaryotic gene expression rely on transcriptional and posttranscriptional regulatory networks. Evolutionary innovations and adaptations often require rapid changes of such networks. It has long been hypothesized that transposable elements (TE might contribute to the rewiring of regulatory interactions. More recently it emerged that TEs might bring in ready-to-use transcription factor binding sites to create alterations to the promoters by which they were captured. A process where the gene regulatory architecture is of remarkable plasticity is sex determination. While the more downstream components of the sex determination cascades are evolutionary conserved, the master regulators can switch between groups of organisms even on the interspecies level or between populations. In the medaka fish (Oryzias latipes a duplicated copy of dmrt1, designated dmrt1bY or DMY, on the Y chromosome was shown to be the master regulator of male development, similar to Sry in mammals. We found that the dmrt1bY gene has acquired a new feedback downregulation of its expression. Additionally, the autosomal dmrt1a gene is also able to regulate transcription of its duplicated paralog by binding to a unique target Dmrt1 site nested within the dmrt1bY proximal promoter region. We could trace back this novel regulatory element to a highly conserved sequence within a new type of TE that inserted into the upstream region of dmrt1bY shortly after the duplication event. Our data provide functional evidence for a role of TEs in transcriptional network rewiring for sub- and/or neo-functionalization of duplicated genes. In the particular case of dmrt1bY, this contributed to create new hierarchies of sex-determining genes.

  1. 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.

  2. Concomitant duplications of opioid peptide and receptor genes before the origin of jawed vertebrates.

    Directory of Open Access Journals (Sweden)

    Görel Sundström

    Full Text Available BACKGROUND: The opioid system is involved in reward and pain mechanisms and consists in mammals of four receptors and several peptides. The peptides are derived from four prepropeptide genes, PENK, PDYN, PNOC and POMC, encoding enkephalins, dynorphins, orphanin/nociceptin and beta-endorphin, respectively. Previously we have described how two rounds of genome doubling (2R before the origin of jawed vertebrates formed the receptor family. METHODOLOGY/PRINCIPAL FINDINGS: Opioid peptide gene family members were investigated using a combination of sequence-based phylogeny and chromosomal locations of the peptide genes in various vertebrates. Several adjacent gene families were investigated similarly. The results show that the ancestral peptide gene gave rise to two additional copies in the genome doublings. The fourth member was generated by a local gene duplication, as the genes encoding POMC and PNOC are located on the same chromosome in the chicken genome and all three teleost genomes that we have studied. A translocation has disrupted this synteny in mammals. The PDYN gene seems to have been lost in chicken, but not in zebra finch. Duplicates of some peptide genes have arisen in the teleost fishes. Within the prepropeptide precursors, peptides have been lost or gained in different lineages. CONCLUSIONS/SIGNIFICANCE: The ancestral peptide and receptor genes were located on the same chromosome and were thus duplicated concomitantly. However, subsequently genetic linkage has been lost. In conclusion, the system of opioid peptides and receptors was largely formed by the genome doublings that took place early in vertebrate evolution.

  3. Gains, losses and changes of function after gene duplication: study of the metallothionein family.

    Directory of Open Access Journals (Sweden)

    Ana Moleirinho

    Full Text Available Metallothioneins (MT are small proteins involved in heavy metal detoxification and protection against oxidative stress and cancer. The mammalian MT family originated through a series of duplication events which generated four major genes (MT1 to MT4. MT1 and MT2 encode for ubiquitous proteins, while MT3 and MT4 evolved to accomplish specific roles in brain and epithelium, respectively. Herein, phylogenetic, transcriptional and polymorphic analyses are carried out to expose gains, losses and diversification of functions that characterize the evolutionary history of the MT family. The phylogenetic analyses show that all four major genes originated through a single duplication event prior to the radiation of mammals. Further expansion of the MT1 gene has occurred in the primate lineage reaching in humans a total of 13 paralogs, five of which are pseudogenes. In humans, the reading frame of all five MT1 pseudogenes is reconstructed by sequence homology with a functional duplicate revealing that loss of invariant cysteines is the most frequent event accounting for pseudogeneisation. Expression analyses based on EST counts and RT-PCR experiments show that, as for MT1 and MT2, human MT3 is also ubiquitously expressed while MT4 transcripts are present in brain, testes, esophagus and mainly in thymus. Polymorphic variation reveals two deleterious mutations (Cys30Tyr and Arg31Trp in MT4 with frequencies reaching about 30% in African and Asian populations suggesting the gene is inactive in some individuals and physiological compensation for its loss must arise from a functional equivalent. Altogether our findings provide novel data on the evolution and diversification of MT gene duplicates, a valuable resource for understanding the vast set of biological processes in which these proteins are involved.

  4. The effect of functional compensation among duplicate genes can constrain their evolutionary divergence

    Indian Academy of Sciences (India)

    Joseph Esfandiar Hannon Bozorgmehr

    2011-04-01

    Gene duplicates have the inherent property of initially being functionally redundant. This means that they can compensate for the effect of deleterious variation occurring at one or more sister sites. Here, I present data bearing on evolutionary theory that illustrates the manner in which any functional adaptation in duplicate genes is markedly constrained because of the compensatory utility provided by a sustained genetic redundancy. Specifically, a two-locus epistatic model of paralogous genes was simulated to investigate the degree of purifying selection imposed, and whether this would serve to impede any possible biochemical innovation. Three population sizes were considered to see if, as expected, there was a significant difference in any selection for robustness. Interestingly, physical linkage between tandem duplicates was actually found to increase the probability of any neofunctionalization and the efficacy of selection, contrary to what is expected in the case of singleton genes. The results indicate that an evolutionary trade-off often exists between any functional change under either positive or relaxed selection and the need to compensate for failures due to degenerative mutations, thereby guaranteeing the reliability of protein production.

  5. Assessment and reconstruction of novel HSP90 genes: duplications, gains and losses in fungal and animal lineages.

    Directory of Open Access Journals (Sweden)

    Chrysoula N Pantzartzi

    Full Text Available Hsp90s, members of the Heat Shock Protein class, protect the structure and function of proteins and play a significant task in cellular homeostasis and signal transduction. In order to determine the number of hsp90 gene copies and encoded proteins in fungal and animal lineages and through that key duplication events that this family has undergone, we collected and evaluated Hsp90 protein sequences and corresponding Expressed Sequence Tags and analyzed available genomes from various taxa. We provide evidence for duplication events affecting either single species or wider taxonomic groups. With regard to Fungi, duplicated genes have been detected in several lineages. In invertebrates, we demonstrate key duplication events in certain clades of Arthropoda and Mollusca, and a possible gene loss event in a hymenopteran family. Finally, we infer that the duplication event responsible for the two (a and b isoforms in vertebrates occurred probably shortly after the split of Hyperoartia and Gnathostomata.

  6. The evolution of pepsinogen C genes in vertebrates: duplication, loss and functional diversification.

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    Luís Filipe Costa Castro

    Full Text Available BACKGROUND: Aspartic proteases comprise a large group of enzymes involved in peptide proteolysis. This collection includes prominent enzymes globally categorized as pepsins, which are derived from pepsinogen precursors. Pepsins are involved in gastric digestion, a hallmark of vertebrate physiology. An important member among the pepsinogens is pepsinogen C (Pgc. A particular aspect of Pgc is its apparent single copy status, which contrasts with the numerous gene copies found for example in pepsinogen A (Pga. Although gene sequences with similarity to Pgc have been described in some vertebrate groups, no exhaustive evolutionary framework has been considered so far. METHODOLOGY/PRINCIPAL FINDINGS: By combining phylogenetics and genomic analysis, we find an unexpected Pgc diversity in the vertebrate sub-phylum. We were able to reconstruct gene duplication timings relative to the divergence of major vertebrate clades. Before tetrapod divergence, a single Pgc gene tandemly expanded to produce two gene lineages (Pgbc and Pgc2. These have been differentially retained in various classes. Accordingly, we find Pgc2 in sauropsids, amphibians and marsupials, but not in eutherian mammals. Pgbc was retained in amphibians, but duplicated in the ancestor of amniotes giving rise to Pgb and Pgc1. The latter was retained in mammals and probably in reptiles and marsupials but not in birds. Pgb was kept in all of the amniote clade with independent episodes of loss in some mammalian species. Lineage specific expansions of Pgc2 and Pgbc have also occurred in marsupials and amphibians respectively. We find that teleost and tetrapod Pgc genes reside in distinct genomic regions hinting at a possible translocation. CONCLUSIONS: We conclude that the repertoire of Pgc genes is larger than previously reported, and that tandem duplications have modelled the history of Pgc genes. We hypothesize that gene expansion lead to functional divergence in tetrapods, coincident with the

  7. Duplication of 7q36.3 encompassing the Sonic Hedgehog (SHH) gene is associated with congenital muscular hypertrophy

    DEFF Research Database (Denmark)

    Kroeldrup, L; Kjaergaard, S; Kirchhoff, Eva Maria

    2012-01-01

    with muscular hypertrophy and mildly retarded psychomotor development. Array-CGH identified a small duplication of 7q36.3 including the Sonic Hedgehog (SHH) gene in both the aborted foetus and the live born male sib. Neither of the parents carried the 7q36.3 duplication. The consequences of overexpression...

  8. The butterfly plant arms-race escalated by gene and genome duplications.

    Science.gov (United States)

    Edger, Patrick P; Heidel-Fischer, Hanna M; Bekaert, Michaël; Rota, Jadranka; Glöckner, Gernot; Platts, Adrian E; Heckel, David G; Der, Joshua P; Wafula, Eric K; Tang, Michelle; Hofberger, Johannes A; Smithson, Ann; Hall, Jocelyn C; Blanchette, Matthieu; Bureau, Thomas E; Wright, Stephen I; dePamphilis, Claude W; Eric Schranz, M; Barker, Michael S; Conant, Gavin C; Wahlberg, Niklas; Vogel, Heiko; Pires, J Chris; Wheat, Christopher W

    2015-07-07

    Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.

  9. A rare case of plastid protein-coding gene duplication in the chloroplast genome of Euglena archaeoplastidiata (Euglenophyta).

    Science.gov (United States)

    Bennett, Matthew S; Shiu, Shin-Han; Triemer, Richard E

    2017-03-12

    Gene duplication is an important evolutionary process that allows duplicate functions to diverge, or, in some cases, allows for new functional gains. However, in contrast to the nuclear genome, gene duplications within the chloroplast are extremely rare. Here, we present the chloroplast genome of the photosynthetic protist Euglena archaeoplastidiata. Upon annotation, it was found that the chloroplast genome contained a novel tandem direct duplication that encoded a portion of RuBisCO large subunit (rbcL) followed by a complete copy of ribosomal protein L32 (rpl32), as well as the associated intergenic sequences. Analyses of the duplicated rpl32 were inconclusive regarding selective pressures, although it was found that substitutions in the duplicated region, all non-synonymous, likely had a neutral functional effect. The duplicated region did not exhibit patterns consistent with previously described mechanisms for tandem direct duplications, and demonstrated an unknown mechanism of duplication. In addition, a comparison of this chloroplast genome to other previously characterized chloroplast genomes from the same family revealed characteristics that indicated E. archaeoplastidiata was probably more closely related to taxa in the genera Monomorphina, Cryptoglena, and Euglenaria than it was to other Euglena taxa. Taken together, the chloroplast genome of E. archaeoplastidiata demonstrated multiple characteristics unique to the euglenoid world, and has justified the longstanding curiosity regarding this enigmatic taxon.

  10. Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1

    Energy Technology Data Exchange (ETDEWEB)

    Hort, Y.; Shine, J.; Herzog, H. [Garvan Inst. of Medical Research, Sydney (Australia)

    1995-03-01

    Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are structurally related but functionally diverse peptides, encoded by separate genes and expressed in different tissues. Although the human NPY gene has been mapped to chromosome 7, the authors demonstrate here that the genes for human PYY and PP (PPY) are localized only 10 kb apart from each another on chromosome 17q21.1. The high degree of homology between the members of this gene family, both in primary sequence and exon/intron structure, suggests that the NYP and the PYY genes arose from an initial gene duplication event, with a subsequent tandem duplication of the PYY gene being responsible for the creation of the PPY gene. A second weaker hybridization signal also found on chromosome 17q11 and results obtained by Southern blot analysis suggest that the entire PYY-PPY region has undergone a further duplication event. 27 refs., 5 figs.

  11. Gene duplications and losses among vertebrate deoxyribonucleoside kinases of the non-TK1 Family

    DEFF Research Database (Denmark)

    Mutahir, Zeeshan; Christiansen, Louise Slot; Clausen, Anders R.;

    2016-01-01

    of the dCK/dGK enzymes encoded by these genes. The two dCK enzymes in G. gallus have broader substrate specificity than their human or X. laevis counterparts. Additionally, the duplicated dCK enzyme in G. gallus might have become mitochondria. Based on our study we postulate that changing and adapting...... substrate specificities and subcellular localization are likely the drivers behind the evolution of vertebrate dNKs...

  12. Whole-Genome Duplications Spurred the Functional Diversification of the Globin Gene Superfamily in Vertebrates

    OpenAIRE

    Hoffmann, Federico G.; Opazo, Juan C; Storz, Jay F.

    2011-01-01

    It has been hypothesized that two successive rounds of whole-genome duplication (WGD) in the stem lineage of vertebrates provided genetic raw materials for the evolutionary innovation of many vertebrate-specific features. However, it has seldom been possible to trace such innovations to specific functional differences between paralogous gene products that derive from a WGD event. Here, we report genomic evidence for a direct link between WGD and key physiological innovations in the vertebrate...

  13. Adaptations to endosymbiosis in a cnidarian-dinoflagellate association: differential gene expression and specific gene duplications.

    Directory of Open Access Journals (Sweden)

    Philippe Ganot

    2011-07-01

    Full Text Available Trophic endosymbiosis between anthozoans and photosynthetic dinoflagellates forms the key foundation of reef ecosystems. Dysfunction and collapse of symbiosis lead to bleaching (symbiont expulsion, which is responsible for the severe worldwide decline of coral reefs. Molecular signals are central to the stability of this partnership and are therefore closely related to coral health. To decipher inter-partner signaling, we developed genomic resources (cDNA library and microarrays from the symbiotic sea anemone Anemonia viridis. Here we describe differential expression between symbiotic (also called zooxanthellate anemones or aposymbiotic (also called bleached A. viridis specimens, using microarray hybridizations and qPCR experiments. We mapped, for the first time, transcript abundance separately in the epidermal cell layer and the gastrodermal cells that host photosynthetic symbionts. Transcriptomic profiles showed large inter-individual variability, indicating that aposymbiosis could be induced by different pathways. We defined a restricted subset of 39 common genes that are characteristic of the symbiotic or aposymbiotic states. We demonstrated that transcription of many genes belonging to this set is specifically enhanced in the symbiotic cells (gastroderm. A model is proposed where the aposymbiotic and therefore heterotrophic state triggers vesicular trafficking, whereas the symbiotic and therefore autotrophic state favors metabolic exchanges between host and symbiont. Several genetic pathways were investigated in more detail: i a key vitamin K-dependant process involved in the dinoflagellate-cnidarian recognition; ii two cnidarian tissue-specific carbonic anhydrases involved in the carbon transfer from the environment to the intracellular symbionts; iii host collagen synthesis, mostly supported by the symbiotic tissue. Further, we identified specific gene duplications and showed that the cnidarian-specific isoform was also up-regulated both

  14. Sub-functionalization to ovule development following duplication of a floral organ identity gene.

    Science.gov (United States)

    Galimba, Kelsey D; Di Stilio, Verónica S

    2015-09-01

    Gene duplications result in paralogs that may be maintained due to the gain of novel functions (neo-functionalization) or the partitioning of ancestral function (sub-functionalization). Plant genomes are especially prone to duplication; paralogs are particularly widespread in the floral MADS box transcription factors that control organ identity through the ABC model of flower development. C class genes establish stamen and carpel identity and control floral meristem determinacy, and are largely conserved across the angiosperm phylogeny. Originally, an additional D class had been identified as controlling ovule identity; yet subsequent studies indicated that both C and D lineage genes more commonly control ovule development redundantly. The ranunculid Thalictrum thalictroides has two orthologs of the Arabidopsis thaliana C class gene AGAMOUS (AG), ThtAG1 and ThtAG2 (Thalictrum thalictroides AGAMOUS1/2). We previously showed that ThtAG1 exhibits typical C class function; here we examine the role of its paralog, ThtAG2. Our phylogenetic analysis shows that ThtAG2 falls within the C lineage, together with ThtAG1, and is consistent with previous findings of a Ranunculales-specific duplication in this clade. However, ThtAG2 is not expressed in stamens, but rather solely in carpels and ovules. This female-specific expression pattern is consistent with D lineage genes, and with other C lineage genes known to be involved in ovule identity. Given the divergent expression of ThtAG2, we tested the hypothesis that it has acquired ovule identity function. Molecular evolution analyses showed evidence of positive selection on ThtAG2-a pattern that supports divergence of function by sub-functionalization. Down-regulation of ThtAG2 by virus-induced gene silencing resulted in homeotic conversions of ovules into carpel-like structures. Taken together, our results suggest that, although ThtAG2 falls within the C lineage, it has diverged to acquire "D function" as an ovule identity gene

  15. Comparative genomic organization and tissue-specific transcription of the duplicated fabp7 and fabp10 genes in teleost fishes.

    Science.gov (United States)

    Parmar, Manoj B; Wright, Jonathan M

    2013-11-01

    A whole-genome duplication (WGD) early in the teleost fish lineage makes fish ideal organisms to study the fate of duplicated genes and underlying evolutionary trajectories that have led to the retention of ohnologous gene duplicates in fish genomes. Here, we compare the genomic organization and tissue-specific transcription of the ohnologous fabp7 and fabp10 genes in medaka, three-spined stickleback, and spotted green pufferfish to the well-studied duplicated fabp7 and fabp10 genes of zebrafish. Teleost fabp7 and fabp10 genes contain four exons interrupted by three introns. Polypeptide sequences of Fabp7 and Fabp10 show the highest sequence identity and similarity with their orthologs from vertebrates. Orthology was evident as the ohnologous Fabp7 and Fabp10 polypeptides of teleost fishes each formed distinct clades and clustered together with their orthologs from other vertebrates in a phylogenetic tree. Furthermore, ohnologous teleost fabp7 and fabp10 genes exhibit conserved gene synteny with human FABP7 and chicken FABP10, respectively, which provides compelling evidence that the duplicated fabp7 and fabp10 genes of teleost fishes most likely arose from the well-documented WGD. The tissue-specific distribution of fabp7a, fabp7b, fabp10a, and fabp10b transcripts provides evidence of diverged spatial transcriptional regulation between ohnologous gene duplicates of fabp7 and fabp10 in teleost fishes.

  16. Evolution history of duplicated smad3 genes in teleost: insights from Japanese flounder, Paralichthys olivaceus

    Directory of Open Access Journals (Sweden)

    Xinxin Du

    2016-09-01

    Full Text Available Following the two rounds of whole-genome duplication (WGD during deuterosome evolution, a third genome duplication occurred in the ray-fined fish lineage and is considered to be responsible for the teleost-specific lineage diversification and regulation mechanisms. As a receptor-regulated SMAD (R-SMAD, the function of SMAD3 was widely studied in mammals. However, limited information of its role or putative paralogs is available in ray-finned fishes. In this study, two SMAD3 paralogs were first identified in the transcriptome and genome of Japanese flounder (Paralichthys olivaceus. We also explored SMAD3 duplication in other selected species. Following identification, genomic structure, phylogenetic reconstruction, and synteny analyses performed by MrBayes and online bioinformatic tools confirmed that smad3a/3b most likely originated from the teleost-specific WGD. Additionally, selection pressure analysis and expression pattern of the two genes performed by PAML and quantitative real-time PCR (qRT-PCR revealed evidence of subfunctionalization of the two SMAD3 paralogs in teleost. Our results indicate that two SMAD3 genes originate from teleost-specific WGD, remain transcriptionally active, and may have likely undergone subfunctionalization. This study provides novel insights to the evolution fates of smad3a/3b and draws attentions to future function analysis of SMAD3 gene family.

  17. Some novel intron positions in conserved Drosophila genes are caused by intron sliding or tandem duplication

    Directory of Open Access Journals (Sweden)

    Stadler Peter F

    2010-05-01

    Full Text Available Abstract Background Positions of spliceosomal introns are often conserved between remotely related genes. Introns that reside in non-conserved positions are either novel or remnants of frequent losses of introns in some evolutionary lineages. A recent gain of such introns is difficult to prove. However, introns verified as novel are needed to evaluate contemporary processes of intron gain. Results We identified 25 unambiguous cases of novel intron positions in 31 Drosophila genes that exhibit near intron pairs (NIPs. Here, a NIP consists of an ancient and a novel intron position that are separated by less than 32 nt. Within a single gene, such closely-spaced introns are very unlikely to have coexisted. In most cases, therefore, the ancient intron position must have disappeared in favour of the novel one. A survey for NIPs among 12 Drosophila genomes identifies intron sliding (migration as one of the more frequent causes of novel intron positions. Other novel introns seem to have been gained by regional tandem duplications of coding sequences containing a proto-splice site. Conclusions Recent intron gains sometimes appear to have arisen by duplication of exonic sequences and subsequent intronization of one of the copies. Intron migration and exon duplication together may account for a significant amount of novel intron positions in conserved coding sequences.

  18. Sox genes in grass carp (Ctenopharyngodon idella with their implications for genome duplication and evolution

    Directory of Open Access Journals (Sweden)

    Tong Jingou

    2006-11-01

    Full Text Available Abstract The Sox gene family is found in a broad range of animal taxa and encodes important gene regulatory proteins involved in a variety of developmental processes. We have obtained clones representing the HMG boxes of twelve Sox genes from grass carp (Ctenopharyngodon idella, one of the four major domestic carps in China. The cloned Sox genes belong to group B1, B2 and C. Our analyses show that whereas the human genome contains a single copy of Sox4, Sox11 and Sox14, each of these genes has two co-orthologs in grass carp, and the duplication of Sox4 and Sox11 occurred before the divergence of grass carp and zebrafish, which support the "fish-specific whole-genome duplication" theory. An estimation for the origin of grass carp based on the molecular clock using Sox1, Sox3 and Sox11 genes as markers indicates that grass carp (subfamily Leuciscinae and zebrafish (subfamily Danioninae diverged approximately 60 million years ago. The potential uses of Sox genes as markers in revealing the evolutionary history of grass carp are discussed.

  19. Divergent Evolutionary Patterns of NAC Transcription Factors Are Associated with Diversification and Gene Duplications in Angiosperm.

    Science.gov (United States)

    Jin, Xiaoli; Ren, Jing; Nevo, Eviatar; Yin, Xuegui; Sun, Dongfa; Peng, Junhua

    2017-01-01

    NAC (NAM/ATAF/CUC) proteins constitute one of the biggest plant-specific transcription factor (TF) families and have crucial roles in diverse developmental programs during plant growth. Phylogenetic analyses have revealed both conserved and lineage-specific NAC subfamilies, among which various origins and distinct features were observed. It is reasonable to hypothesize that there should be divergent evolutionary patterns of NAC TFs both between dicots and monocots, and among NAC subfamilies. In this study, we compared the gene duplication and loss, evolutionary rate, and selective pattern among non-lineage specific NAC subfamilies, as well as those between dicots and monocots, through genome-wide analyses of sequence and functional data in six dicot and five grass lineages. The number of genes gained in the dicot lineages was much larger than that in the grass lineages, while fewer gene losses were observed in the grass than that in the dicots. We revealed (1) uneven constitution of Clusters of Orthologous Groups (COGs) and contrasting birth/death rates among subfamilies, and (2) two distinct evolutionary scenarios of NAC TFs between dicots and grasses. Our results demonstrated that relaxed selection, resulting from concerted gene duplications, may have permitted substitutions responsible for functional divergence of NAC genes into new lineages. The underlying mechanism of distinct evolutionary fates of NAC TFs shed lights on how evolutionary divergence contributes to differences in establishing NAC gene subfamilies and thus impacts the distinct features between dicots and grasses.

  20. Divergent Evolutionary Patterns of NAC Transcription Factors Are Associated with Diversification and Gene Duplications in Angiosperm

    Directory of Open Access Journals (Sweden)

    Xiaoli Jin

    2017-06-01

    Full Text Available NAC (NAM/ATAF/CUC proteins constitute one of the biggest plant-specific transcription factor (TF families and have crucial roles in diverse developmental programs during plant growth. Phylogenetic analyses have revealed both conserved and lineage-specific NAC subfamilies, among which various origins and distinct features were observed. It is reasonable to hypothesize that there should be divergent evolutionary patterns of NAC TFs both between dicots and monocots, and among NAC subfamilies. In this study, we compared the gene duplication and loss, evolutionary rate, and selective pattern among non-lineage specific NAC subfamilies, as well as those between dicots and monocots, through genome-wide analyses of sequence and functional data in six dicot and five grass lineages. The number of genes gained in the dicot lineages was much larger than that in the grass lineages, while fewer gene losses were observed in the grass than that in the dicots. We revealed (1 uneven constitution of Clusters of Orthologous Groups (COGs and contrasting birth/death rates among subfamilies, and (2 two distinct evolutionary scenarios of NAC TFs between dicots and grasses. Our results demonstrated that relaxed selection, resulting from concerted gene duplications, may have permitted substitutions responsible for functional divergence of NAC genes into new lineages. The underlying mechanism of distinct evolutionary fates of NAC TFs shed lights on how evolutionary divergence contributes to differences in establishing NAC gene subfamilies and thus impacts the distinct features between dicots and grasses.

  1. The role of human-specific gene duplications during brain development and evolution.

    Science.gov (United States)

    Sassa, Takayuki

    2013-09-01

    One of the most fascinating questions in evolutionary biology is how traits unique to humans, such as their high cognitive abilities, erect bipedalism, and hairless skin, are encoded in the genome. Recent advances in genomics have begun to reveal differences between the genomes of the great apes. It has become evident that one of the many mutation types, segmental duplication, has drastically increased in the primate genomes, and most remarkably in the human genome. Genes contained in these segmental duplications have a tremendous potential to cause genetic innovation, probably accounting for the acquisition of human-specific traits. In this review, I begin with an overview of the genes, which have increased their copy number specifically in the human lineage, following its separation from the common ancestor with our closest living relative, the chimpanzee. Then, I introduce the recent experimental approaches, focusing on SRGAP2, which has been partially duplicated, to elucidate the role of SRGAP2 protein and its human-specific paralogs in human brain development and evolution.

  2. The Role of Cis-Regulatory Motifs and Genetical Control of Expression in the Divergence of Yeast Duplicate Genes

    National Research Council Canada - National Science Library

    Leach, Lindsey J; Zhang, Ze; Lu, Chenqi; Kearsey, Michael J; Luo, Zewei

    2007-01-01

    Expression divergence of duplicate genes is widely believed to be important for their retention and evolution of new function, although the mechanism that determines their expression divergence remains unclear...

  3. Historical profiling of maize duplicate genes sheds light on the evolution of C4 photosynthesis in grasses.

    Science.gov (United States)

    Chang, Yao-Ming; Chang, Chia-Lin; Li, Wen-Hsiung; Shih, Arthur Chun-Chieh

    2013-02-01

    C4 plants evolved from C3 plants through a series of complex evolutionary steps. On the basis of the evolution of key C4 enzyme genes, the evolution of C4 photosynthesis has been considered a story of gene/genome duplications and subsequent modifications of gene function. If whole-genome duplication has contributed to the evolution of C4 photosynthesis, other genes should have been duplicated together with these C4 genes. However, which genes were co-duplicated with C4 genes and whether they have also played a role in C4 evolution are largely unknown. In this study, we developed a simple method to characterize the historical profile of the paralogs of a gene by tracing back to the most recent common ancestor (MRCA) of the gene and its paralog(s) and then counting the number of paralogs at each MRCA. We clustered the genes into clusters with similar duplication profiles and inferred their functional enrichments. Applying our method to maize, a familiar C4 plant, we identified many genes that show similar duplication profiles with those of the key C4 enzyme genes and found that the functional preferences of the C4 gene clusters are not only similar to those identified by an experimental approach in a recent study but also highly consistent with the functions required for the C4 photosynthesis evolutionary model proposed by S.F. Sage. Some of these genes might have co-evolved with the key C4 enzyme genes to increase the strength of C4 photosynthesis. Moreover, our results suggested that most key C4 enzyme genes had different origins and have undergone a long evolutionary process before the emergence of C4 grasses (Andropogoneae), consistent with the conclusion proposed by previous authors. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Identification of genes that are essential to restrict genome duplication to once per cell division

    Science.gov (United States)

    Vassilev, Alex; Lee, Chrissie Y.; Vassilev, Boris; Zhu, Wenge; Ormanoglu, Pinar; Martin, Scott E.; DePamphilis, Melvin L.

    2016-01-01

    Nuclear genome duplication is normally restricted to once per cell division, but aberrant events that allow excess DNA replication (EDR) promote genomic instability and aneuploidy, both of which are characteristics of cancer development. Here we provide the first comprehensive identification of genes that are essential to restrict genome duplication to once per cell division. An siRNA library of 21,584 human genes was screened for those that prevent EDR in cancer cells with undetectable chromosomal instability. Candidates were validated by testing multiple siRNAs and chemical inhibitors on both TP53+ and TP53- cells to reveal the relevance of this ubiquitous tumor suppressor to preventing EDR, and in the presence of an apoptosis inhibitor to reveal the full extent of EDR. The results revealed 42 genes that prevented either DNA re-replication or unscheduled endoreplication. All of them participate in one or more of eight cell cycle events. Seventeen of them have not been identified previously in this capacity. Remarkably, 14 of the 42 genes have been shown to prevent aneuploidy in mice. Moreover, suppressing a gene that prevents EDR increased the ability of the chemotherapeutic drug Paclitaxel to induce EDR, suggesting new opportunities for synthetic lethalities in the treatment of human cancers. PMID:27144335

  5. The maize auxotrophic mutant orange pericarp is defective in duplicate genes for tryptophan synthase beta.

    Science.gov (United States)

    Wright, A D; Moehlenkamp, C A; Perrot, G H; Neuffer, M G; Cone, K C

    1992-06-01

    orange pericarp (orp) is a seedling lethal mutant of maize caused by mutations in the duplicate unlinked recessive loci orp1 and orp2. Mutant seedlings accumulate two tryptophan precursors, anthranilate and indole, suggesting a block in tryptophan biosynthesis. Results from feeding studies and enzyme assays indicate that the orp mutant is defective in tryptophan synthase beta activity. Thus, orp is one of only a few amino acid auxotrophic mutants to be characterized in plants. Two genes encoding tryptophan synthase beta were isolated from maize and sequenced. Both genes encode polypeptides with high homology to tryptophan synthase beta enzymes from other organisms. The cloned genes were mapped by restriction fragment length polymorphism analysis to approximately the same chromosomal locations as the genetically mapped factors orp1 and orp2. RNA analysis indicates that both genes are expressed in all tissues examined from normal plants. Together, the biochemical, genetic, and molecular data verify the identity of orp1 and orp2 as duplicate structural genes for the beta subunit of tryptophan synthase.

  6. Adaptive evolution after gene duplication in alpha-KT x 14 subfamily from Buthus martensii Karsch.

    Science.gov (United States)

    Cao, Zhijian; Mao, Xin; Xu, Xiuling; Sheng, Jiqun; Dai, Chao; Wu, Yingliang; Luo, Feng; Sha, Yonggang; Jiang, Dahe; Li, Wenxin

    2005-07-01

    A series of isoforms of alpha-KT x 14 (short chain potassium channel scorpion toxins) were isolated from the venom of Buthus martensii Karsch by RACE and screening cDNA library methods. These isoforms adding BmKK1--3 and BmSKTx1--2 together shared high homology (more than 97%) with each other. The result of genomic sequence analysis showed that a length 79 bp intron is inserted Ala codes between the first and the second base at the 17th amino acid of signal peptide. The introns of these isoforms also share high homology with those of BmKK2 and BmSKT x 1 reported previously. Sequence analysis of many clones of cDNA and genomic DNA showed that a species population or individual polymorphism of alpha-KT x 14 genes took place in scorpion Buthus martensii Karsch and accelerated evolution played an important role in the forming process of alpha-KT x 14 scorpion toxins subfamily. The result of southern hybridization indicated that alpha-KT x 14 toxin genes existed in scorpion chromosome with multicopies. All findings maybe provided an important evidence for an extensive evolutionary process of the scorpion "pharmacological factory": at the early course of evolution, the ancestor toxic gene duplicated into a series of multicopy genes integrated at the different chromosome; at the late course of evolution, subsequent functional divergence of duplicate genes was generated by mutations, deletions and insertion.

  7. Impact of duplicate gene copies on phylogenetic analysis and divergence time estimates in butterflies

    Directory of Open Access Journals (Sweden)

    Liswi Saif W

    2009-05-01

    Full Text Available Abstract Background The increase in availability of genomic sequences for a wide range of organisms has revealed gene duplication to be a relatively common event. Encounters with duplicate gene copies have consequently become almost inevitable in the context of collecting gene sequences for inferring species trees. Here we examine the effect of incorporating duplicate gene copies evolving at different rates on tree reconstruction and time estimation of recent and deep divergences in butterflies. Results Sequences from ultraviolet-sensitive (UVRh, blue-sensitive (BRh, and long-wavelength sensitive (LWRh opsins,EF-1α and COI were obtained from 27 taxa representing the five major butterfly families (5535 bp total. Both BRh and LWRh are present in multiple copies in some butterfly lineages and the different copies evolve at different rates. Regardless of the phylogenetic reconstruction method used, we found that analyses of combined data sets using either slower or faster evolving copies of duplicate genes resulted in a single topology in agreement with our current understanding of butterfly family relationships based on morphology and molecules. Interestingly, individual analyses of BRh and LWRh sequences also recovered these family-level relationships. Two different relaxed clock methods resulted in similar divergence time estimates at the shallower nodes in the tree, regardless of whether faster or slower evolving copies were used, with larger discrepancies observed at deeper nodes in the phylogeny. The time of divergence between the monarch butterfly Danaus plexippus and the queen D. gilippus (15.3–35.6 Mya was found to be much older than the time of divergence between monarch co-mimic Limenitis archippus and red-spotted purple L. arthemis (4.7–13.6 Mya, and overlapping with the time of divergence of the co-mimetic passionflower butterflies Heliconius erato and H. melpomene (13.5–26.1 Mya. Our family-level results are congruent with

  8. The transformer genes in the fig wasp Ceratosolen solmsi provide new evidence for duplications independent of complementary sex determination.

    Science.gov (United States)

    Jia, L-Y; Xiao, J-H; Xiong, T-L; Niu, L-M; Huang, D-W

    2016-06-01

    Transformer (tra) is the key gene that turns on the sex-determination cascade in Drosophila melanogaster and in some other insects. The honeybee Apis mellifera has two duplicates of tra, one of which (complementary sex determiner, csd) is the primary signal for complementary sex-determination (CSD), regulating the other duplicate (feminizer). Two tra duplicates have been found in some other hymenopteran species, resulting in the assumption that a single ancestral duplication of tra took place in the Hymenoptera. Here, we searched for tra homologues and pseudogenes in the Hymenoptera, focusing on five newly published hymenopteran genomes. We found three tra copies in the fig wasp Ceratosolen solmsi. Further evolutionary and expression analyses also showed that the two duplicates (Csoltra-B and Csoltra-C) are under positive selection, and have female-specific expression, suggesting possible sex-related functions. Moreover, Aculeata species exhibit many pseudogenes generated by lineage-specific duplications. We conclude that phylogenetic reconstruction and pseudogene screening provide novel evidence supporting the hypothesis of independent duplications rather an ancestral origin of multiple tra paralogues in the Hymenoptera. The case of C. solmsi is the first example of a non-CSD species with duplicated tra, contrary to the previous assumption that derived tra paralogues function as the CSD locus. © 2016 The Royal Entomological Society.

  9. Duplication and amplification of antibiotic resistance genes enable increased resistance in isolates of multidrug-resistant Salmonella Typhimurium

    Science.gov (United States)

    During normal bacterial DNA replication, gene duplication and amplification (GDA) events occur randomly at a low frequency in the genome throughout a population. In the absence of selection, GDA events that increase the number of copies of a bacterial gene (or a set of genes) are lost. Antibiotic ...

  10. Gene Duplication and the Evolution of Plant MADS-box Transcription Factors

    Institute of Scientific and Technical Information of China (English)

    Chiara A. Airoldi; Brendan Davies

    2012-01-01

    Since the first MADS-box transcription factor genes were implicated in the establishment of floral organ identity in a couple of model plants,the size and scope of this gene family has begun to be appreciated in a much wider range of species.Over the course of millions of years the number of MADS-box genes in plants has increased to the point that the Arabidopsis genome contains more than 100.The understanding gained from studying the evolution,regulation and function of multiple MADS-box genes in an increasing set of species,makes this large plant transcription factor gene family an ideal subject to study the processes that lead to an increase in gene number and the selective birth,death and repurposing of its component members.Here we will use examples taken from the MADS-box gene family to review what is known about the factors that influence the loss and retention of genes duplicated in different ways and examine the varied fates of the retained genes and their associated biological outcomes.

  11. Multiple tandem duplication of the phenylalanine ammonia-lyase genes in Cucumis sativus L.

    Science.gov (United States)

    Shang, Qing-Mao; Li, Liang; Dong, Chun-Juan

    2012-10-01

    Phenylalanine ammonia-lyase (PAL) is the first entry enzyme of the phenylpropanoid pathway, and therefore plays a key role in both plant development and stress defense. In many plants, PAL is encoded by a multi-gene family, and each member is differentially regulated in response to environmental stimuli. In the present study, we report that PAL in cucumber (Cucumis sativus L.) is encoded for by a family of seven genes (designated as CsPAL1-7). All seven CsPALs are arranged in tandem in two duplication blocks, which are located on chromosomes 4 and 6, respectively. The cDNA and protein sequences of the CsPALs share an overall high identity to each other. Homology modeling reveals similarities in their protein structures, besides several slight differences, implying the different activities in conversion of phenylalanine. Phylogenic analysis places CsPAL1-7 in a separate cluster rather than clustering with other plant PALs. Analyses of expression profiles in different cucumber tissues or in response to various stress or plant hormone treatments indicate that CsPAL1-7 play redundant, but divergent roles in cucumber development and stress response. This is consistent with our finding that CsPALs possess overlapping but different cis-elements in their promoter regions. Finally, several duplication events are discussed to explain the evolution of the cucumber PAL genes.

  12. Insights into the coupling of duplication events and macroevolution from an age profile of animal transmembrane gene families.

    Directory of Open Access Journals (Sweden)

    Guohui Ding

    2006-08-01

    Full Text Available The evolution of new gene families subsequent to gene duplication may be coupled to the fluctuation of population and environment variables. Based upon that, we presented a systematic analysis of the animal transmembrane gene duplication events on a macroevolutionary scale by integrating the palaeontology repository. The age of duplication events was calculated by maximum likelihood method, and the age distribution was estimated by density histogram and normal kernel density estimation. We showed that the density of the duplicates displays a positive correlation with the estimates of maximum number of cell types of common ancestors, and the oxidation events played a key role in the major transitions of this density trace. Next, we focused on the Phanerozoic phase, during which more macroevolution data are available. The pulse mass extinction timepoints coincide with the local peaks of the age distribution, suggesting that the transmembrane gene duplicates fixed frequently when the environment changed dramatically. Moreover, a 61-million-year cycle is the most possible cycle in this phase by spectral analysis, which is consistent with the cycles recently detected in biodiversity. Our data thus elucidate a strong coupling of duplication events and macroevolution; furthermore, our method also provides a new way to address these questions.

  13. Duplication and divergent evolution of the CHS and CHS-like genes in the chalcone synthase (CHS) superfamily

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The enzymes of the CHS-superfamily are responsible for biosynthesis of a wide range of natural products in plants. They are important for flower pigmentation, protection against UV light and defense against phytopathogens. Many plants were found to contain multiple copies of CHS genes. This review summarizes the recent progress in the studies of the CHS-superfamily, focusing on the duplication and divergent evolution of the CHS and CHS-like genes. Comparative analyses of gene structure, expression patterns and catalytic properties revealed extensive differentiation in both regulation and function among duplicate CHS genes. It is also proposed that the CHS-like enzymes in the CHS-superfamily evolved from CHS at different times in various organisms. The CHS-superfamily thus offers a valuable model to study the rates and patterns of sequence divergence between duplicate genes.

  14. Characterization of genes encoding poly(A polymerases in plants: evidence for duplication and functional specialization.

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    Lisa R Meeks

    Full Text Available BACKGROUND: Poly(A polymerase is a key enzyme in the machinery that mediates mRNA 3' end formation in eukaryotes. In plants, poly(A polymerases are encoded by modest gene families. To better understand this multiplicity of genes, poly(A polymerase-encoding genes from several other plants, as well as from Selaginella, Physcomitrella, and Chlamydomonas, were studied. METHODOLOGY/PRINCIPAL FINDINGS: Using bioinformatics tools, poly(A polymerase-encoding genes were identified in the genomes of eight species in the plant lineage. Whereas Chlamydomonas reinhardtii was found to possess a single poly(A polymerase gene, other species possessed between two and six possible poly(A polymerase genes. With the exception of four intron-lacking genes, all of the plant poly(A polymerase genes (but not the C. reinhardtii gene possessed almost identical intron positions within the poly(A polymerase coding sequences, suggesting that all plant poly(A polymerase genes derive from a single ancestral gene. The four Arabidopsis poly(A polymerase genes were found to be essential, based on genetic analysis of T-DNA insertion mutants. GFP fusion proteins containing three of the four Arabidopsis poly(A polymerases localized to the nucleus, while one such fusion protein was localized in the cytoplasm. The fact that this latter protein is largely pollen-specific suggests that it has important roles in male gametogenesis. CONCLUSIONS/SIGNIFICANCE: Our results indicate that poly(A polymerase genes have expanded from a single ancestral gene by a series of duplication events during the evolution of higher plants, and that individual members have undergone sorts of functional specialization so as to render them essential for plant growth and development. Perhaps the most interesting of the plant poly(A polymerases is a novel cytoplasmic poly(A polymerase that is expressed in pollen in Arabidopsis; this is reminiscent of spermatocyte-specific cytoplasmic poly(A polymerases in

  15. Correlating Traits of Gene Retention, Sequence Divergence, Duplicability and Essentiality in Vertebrates, Arthropods, and Fungi

    Science.gov (United States)

    Waterhouse, Robert M.; Zdobnov, Evgeny M.; Kriventseva, Evgenia V.

    2011-01-01

    Delineating ancestral gene relations among a large set of sequenced eukaryotic genomes allowed us to rigorously examine links between evolutionary and functional traits. We classified 86% of over 1.36 million protein-coding genes from 40 vertebrates, 23 arthropods, and 32 fungi into orthologous groups and linked over 90% of them to Gene Ontology or InterPro annotations. Quantifying properties of ortholog phyletic retention, copy-number variation, and sequence conservation, we examined correlations with gene essentiality and functional traits. More than half of vertebrate, arthropod, and fungal orthologs are universally present across each lineage. These universal orthologs are preferentially distributed in groups with almost all single-copy or all multicopy genes, and sequence evolution of the predominantly single-copy orthologous groups is markedly more constrained. Essential genes from representative model organisms, Mus musculus, Drosophila melanogaster, and Saccharomyces cerevisiae, are significantly enriched in universal orthologs within each lineage, and essential-gene-containing groups consistently exhibit greater sequence conservation than those without. This study of eukaryotic gene repertoire evolution identifies shared fundamental principles and highlights lineage-specific features, it also confirms that essential genes are highly retained and conclusively supports the “knockout-rate prediction” of stronger constraints on essential gene sequence evolution. However, the distinction between sequence conservation of single- versus multicopy orthologs is quantitatively more prominent than between orthologous groups with and without essential genes. The previously underappreciated difference in the tolerance of gene duplications and contrasting evolutionary modes of “single-copy control” versus “multicopy license” may reflect a major evolutionary mechanism that allows extended exploration of gene sequence space. PMID:21148284

  16. Neofunctionalization of a duplicate hatching enzyme gene during the evolution of teleost fishes.

    Science.gov (United States)

    Sano, Kaori; Kawaguchi, Mari; Watanabe, Satoshi; Yasumasu, Shigeki

    2014-10-19

    Duplication and subsequent neofunctionalization of the teleostean hatching enzyme gene occurred in the common ancestor of Euteleostei and Otocephala, producing two genes belonging to different phylogenetic clades (clade I and II). In euteleosts, the clade I enzyme inherited the activity of the ancestral enzyme of swelling the egg envelope by cleavage of the N-terminal region of egg envelope proteins. The clade II enzyme gained two specific cleavage sites, N-ZPd and mid-ZPd but lost the ancestral activity. Thus, euteleostean clade II enzymes assumed a new function; solubilization of the egg envelope by the cooperative action with clade I enzyme. However, in Otocephala, the clade II gene was lost during evolution. Consequently, in a late group of Otocephala, only the clade I enzyme is present to swell the egg envelope. We evaluated the egg envelope digestion properties of clade I and II enzymes in Gonorynchiformes, an early diverging group of Otocephala, using milkfish, and compared their digestion with those of other fishes. Finally, we propose a hypothesis of the neofunctionalization process. The milkfish clade II enzyme cleaved N-ZPd but not mid-ZPd, and did not cause solubilization of the egg envelope. We conclude that neofunctionalization is incomplete in the otocephalan clade II enzymes. Comparison of clade I and clade II enzyme characteristics implies that the specificity of the clade II enzymes gradually changed during evolution after the duplication event, and that a change in substrate was required for the addition of the mid-ZPd site and loss of activity at the N-terminal region. We infer the process of neofunctionalization of the clade II enzyme after duplication of the gene. The ancestral clade II gene gained N-ZPd cleavage activity in the common ancestral lineage of the Euteleostei and Otocephala. Subsequently, acquisition of cleavage activity at the mid-ZPd site and loss of cleavage activity in the N-terminal region occurred during the evolution of

  17. Gene duplication and adaptive evolution of digestive proteases in Drosophila arizonae female reproductive tracts.

    Directory of Open Access Journals (Sweden)

    Erin S Kelleher

    2007-08-01

    Full Text Available It frequently has been postulated that intersexual coevolution between the male ejaculate and the female reproductive tract is a driving force in the rapid evolution of reproductive proteins. The dearth of research on female tracts, however, presents a major obstacle to empirical tests of this hypothesis. Here, we employ a comparative EST approach to identify 241 candidate female reproductive proteins in Drosophila arizonae, a repleta group species in which physiological ejaculate-female coevolution has been documented. Thirty-one of these proteins exhibit elevated amino acid substitution rates, making them candidates for molecular coevolution with the male ejaculate. Strikingly, we also discovered 12 unique digestive proteases whose expression is specific to the D. arizonae lower female reproductive tract. These enzymes belong to classes most commonly found in the gastrointestinal tracts of a diverse array of organisms. We show that these proteases are associated with recent, lineage-specific gene duplications in the Drosophila repleta species group, and exhibit strong signatures of positive selection. Observation of adaptive evolution in several female reproductive tract proteins indicates they are active players in the evolution of reproductive tract interactions. Additionally, pervasive gene duplication, adaptive evolution, and rapid acquisition of a novel digestive function by the female reproductive tract points to a novel coevolutionary mechanism of ejaculate-female interaction.

  18. On the origin of protein synthesis factors: a gene duplication/fusion model.

    Science.gov (United States)

    Cousineau, B; Leclerc, F; Cedergren, R

    1997-12-01

    Sequence similarity has given rise to the proposal that IF-2, EF-G, and EF-Tu are related through a common ancestor. We evaluate this proposition and whether the relationship can be extended to other factors of protein synthesis. Analysis of amino acid sequence similarity gives statistical support for an evolutionary affiliation among IF-1, IF-2, IF-3, EF-Tu, EF-Ts, and EF-G and suggests further that this association is a result of gene duplication/fusion events. In support of this mechanism, the three-dimensional structures of IF-3, EF-Tu, and EF-G display a predictable domain structure and overall conformational similarity. The model that we propose consists of three consecutives duplication/fusion events which would have taken place before the divergence of the three superkingdoms: eubacteria, archaea, and eukaryotes. The root of this protein superfamily tree would be an ancestor of the modern IF-1 gene sequence. The repeated fundamental motif of this protein superfamily is a small RNA binding domain composed of two alpha-helices packed along side of an antiparallel beta-sheet.

  19. New organelles by gene duplication in a biophysical model of eukaryote endomembrane evolution.

    Science.gov (United States)

    Ramadas, Rohini; Thattai, Mukund

    2013-06-04

    Extant eukaryotic cells have a dynamic traffic network that consists of diverse membrane-bound organelles exchanging matter via vesicles. This endomembrane system arose and diversified during a period characterized by massive expansions of gene families involved in trafficking after the acquisition of a mitochondrial endosymbiont by a prokaryotic host cell >1.8 billion years ago. Here we investigate the mechanistic link between gene duplication and the emergence of new nonendosymbiotic organelles, using a minimal biophysical model of traffic. Our model incorporates membrane-bound compartments, coat proteins and adaptors that drive vesicles to bud and segregate cargo from source compartments, and SNARE proteins and associated factors that cause vesicles to fuse into specific destination compartments. In simulations, arbitrary numbers of compartments with heterogeneous initial compositions segregate into a few compositionally distinct subsets that we term organelles. The global structure of the traffic system (i.e., the number, composition, and connectivity of organelles) is determined completely by local molecular interactions. On evolutionary timescales, duplication of the budding and fusion machinery followed by loss of cross-interactions leads to the emergence of new organelles, with increased molecular specificity being necessary to maintain larger organellar repertoires. These results clarify potential modes of early eukaryotic evolution as well as more recent eukaryotic diversification. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  20. The impact of gene duplication, insertion, deletion, lateral gene transfer and sequencing error on orthology inference: a simulation study.

    Science.gov (United States)

    Dalquen, Daniel A; Altenhoff, Adrian M; Gonnet, Gaston H; Dessimoz, Christophe

    2013-01-01

    The identification of orthologous genes, a prerequisite for numerous analyses in comparative and functional genomics, is commonly performed computationally from protein sequences. Several previous studies have compared the accuracy of orthology inference methods, but simulated data has not typically been considered in cross-method assessment studies. Yet, while dependent on model assumptions, simulation-based benchmarking offers unique advantages: contrary to empirical data, all aspects of simulated data are known with certainty. Furthermore, the flexibility of simulation makes it possible to investigate performance factors in isolation of one another.Here, we use simulated data to dissect the performance of six methods for orthology inference available as standalone software packages (Inparanoid, OMA, OrthoInspector, OrthoMCL, QuartetS, SPIMAP) as well as two generic approaches (bidirectional best hit and reciprocal smallest distance). We investigate the impact of various evolutionary forces (gene duplication, insertion, deletion, and lateral gene transfer) and technological artefacts (ambiguous sequences) on orthology inference. We show that while gene duplication/loss and insertion/deletion are well handled by most methods (albeit for different trade-offs of precision and recall), lateral gene transfer disrupts all methods. As for ambiguous sequences, which might result from poor sequencing, assembly, or genome annotation, we show that they affect alignment score-based orthology methods more strongly than their distance-based counterparts.

  1. The impact of gene duplication, insertion, deletion, lateral gene transfer and sequencing error on orthology inference: a simulation study.

    Directory of Open Access Journals (Sweden)

    Daniel A Dalquen

    Full Text Available The identification of orthologous genes, a prerequisite for numerous analyses in comparative and functional genomics, is commonly performed computationally from protein sequences. Several previous studies have compared the accuracy of orthology inference methods, but simulated data has not typically been considered in cross-method assessment studies. Yet, while dependent on model assumptions, simulation-based benchmarking offers unique advantages: contrary to empirical data, all aspects of simulated data are known with certainty. Furthermore, the flexibility of simulation makes it possible to investigate performance factors in isolation of one another.Here, we use simulated data to dissect the performance of six methods for orthology inference available as standalone software packages (Inparanoid, OMA, OrthoInspector, OrthoMCL, QuartetS, SPIMAP as well as two generic approaches (bidirectional best hit and reciprocal smallest distance. We investigate the impact of various evolutionary forces (gene duplication, insertion, deletion, and lateral gene transfer and technological artefacts (ambiguous sequences on orthology inference. We show that while gene duplication/loss and insertion/deletion are well handled by most methods (albeit for different trade-offs of precision and recall, lateral gene transfer disrupts all methods. As for ambiguous sequences, which might result from poor sequencing, assembly, or genome annotation, we show that they affect alignment score-based orthology methods more strongly than their distance-based counterparts.

  2. Sgs1 and Exo1 suppress targeted chromosome duplication during ends-in and ends-out gene targeting.

    Science.gov (United States)

    Štafa, Anamarija; Miklenić, Marina; Zunar, Bojan; Lisnić, Berislav; Symington, Lorraine S; Svetec, Ivan-Krešimir

    2014-10-01

    Gene targeting is extremely efficient in the yeast Saccharomyces cerevisiae. It is performed by transformation with a linear, non-replicative DNA fragment carrying a selectable marker and containing ends homologous to the particular locus in a genome. However, even in S. cerevisiae, transformation can result in unwanted (aberrant) integration events, the frequency and spectra of which are quite different for ends-out and ends-in transformation assays. It has been observed that gene replacement (ends-out gene targeting) can result in illegitimate integration, integration of the transforming DNA fragment next to the target sequence and duplication of a targeted chromosome. By contrast, plasmid integration (ends-in gene targeting) is often associated with multiple targeted integration events but illegitimate integration is extremely rare and a targeted chromosome duplication has not been reported. Here we systematically investigated the influence of design of the ends-out assay on the success of targeted genetic modification. We have determined transformation efficiency, fidelity of gene targeting and spectra of all aberrant events in several ends-out gene targeting assays designed to insert, delete or replace a particular sequence in the targeted region of the yeast genome. Furthermore, we have demonstrated for the first time that targeted chromosome duplications occur even during ends-in gene targeting. Most importantly, the whole chromosome duplication is POL32 dependent pointing to break-induced replication (BIR) as the underlying mechanism. Moreover, the occurrence of duplication of the targeted chromosome was strikingly increased in the exo1Δ sgs1Δ double mutant but not in the respective single mutants demonstrating that the Exo1 and Sgs1 proteins independently suppress whole chromosome duplication during gene targeting.

  3. Evolutionary history of c-myc in teleosts and characterization of the duplicated c-myca genes in goldfish embryos.

    Science.gov (United States)

    Marandel, Lucie; Labbe, Catherine; Bobe, Julien; Le Bail, Pierre-Yves

    2012-02-01

    c-Myc plays an important role during embryogenesis in mammals, but little is known about its function during embryonic development in teleosts. In addition, the evolutionary history of c-myc gene in teleosts remains unclear, and depending on the species, a variable number of gene duplicates exist in teleosts. To gain new insight into c-myc genes in teleosts, the present study was designed to clarify the evolutionary history of c-myc gene(s) in teleosts and to subsequently characterize DNA methylation and early embryonic expression patterns in a cyprinid fish. Our results show that a duplication of c-myc gene occurred before or around the teleost radiation, as a result of the teleost-specific whole genome duplication giving rise to c-myca and c-mycb in teleosts and was followed by a loss of the c-mycb gene in the Gasterosteiforms and Tetraodontiforms. Our data also demonstrate that both c-myc genes previously identified in carp and goldfish are co-orthologs of the zebrafish c-myca. These results indicate the presence of additional c-myca duplication in Cyprininae. We were able to identify differences between the expression patterns of the two goldfish c-myca genes in oocytes and early embryos. These differences suggest a partial sub-functionalization of c-myca genes after duplication. Despite differences in transcription patterns, both of the c-myca genes displayed similar DNA methylation patterns during early development and in gametes. Together, our results clarify the evolutionary history of the c-myc gene in teleosts and provide new insight into the involvement of c-myc in early embryonic development in cyprinids. Copyright © 2011 Wiley Periodicals, Inc.

  4. A 380-kb Duplication in 7p22.3 Encompassing the LFNG Gene in a Boy with Asperger Syndrome

    NARCIS (Netherlands)

    Vulto-van Silfhout, A.T.; Brouwer, A.F. de; Leeuw, N. de; Obihara, C.C.; Brunner, H.G.; Vries, B.B. de

    2012-01-01

    De novo genomic aberrations are considered an important cause of autism spectrum disorders. We describe a de novo 380-kb gain in band p22.3 of chromosome 7 in a patient with Asperger syndrome. This duplicated region contains 9 genes including the LNFG gene that is an important regulator of NOTCH

  5. A 380-kb Duplication in 7p22.3 Encompassing the LFNG Gene in a Boy with Asperger Syndrome

    NARCIS (Netherlands)

    Vulto-van Silfhout, A.T.; Brouwer, A.F. de; Leeuw, N. de; Obihara, C.C.; Brunner, H.G.; Vries, B.B. de

    2012-01-01

    De novo genomic aberrations are considered an important cause of autism spectrum disorders. We describe a de novo 380-kb gain in band p22.3 of chromosome 7 in a patient with Asperger syndrome. This duplicated region contains 9 genes including the LNFG gene that is an important regulator of NOTCH sig

  6. A 380-kb Duplication in 7p22.3 Encompassing the LFNG Gene in a Boy with Asperger Syndrome

    NARCIS (Netherlands)

    Vulto-van Silfhout, A.T.; Brouwer, A.F. de; Leeuw, N. de; Obihara, C.C.; Brunner, H.G.; Vries, B.B. de

    2012-01-01

    De novo genomic aberrations are considered an important cause of autism spectrum disorders. We describe a de novo 380-kb gain in band p22.3 of chromosome 7 in a patient with Asperger syndrome. This duplicated region contains 9 genes including the LNFG gene that is an important regulator of NOTCH sig

  7. Duplication of the NPHP1 gene in patients with autism spectrum disorder and normal intellectual ability: a case series.

    Science.gov (United States)

    Yasuda, Yuka; Hashimoto, Ryota; Fukai, Ryoko; Okamoto, Nobuhiko; Hiraki, Yoko; Yamamori, Hidenaga; Fujimoto, Michiko; Ohi, Kazutaka; Taniike, Masako; Mohri, Ikuko; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Matsumoto, Naomichi; Miyake, Noriko; Takeda, Masatoshi

    2014-01-01

    Autism spectrum disorder is a neurodevelopmental disorder characterized by impairments in social interactions, reduced verbal communication abilities, stereotyped repetitive behaviors, and restricted interests. It is a complex condition caused by genetic and environmental factors; the high heritability of this disorder supports the presence of a significant genetic contribution. Many studies have suggested that copy-number variants contribute to the etiology of autism spectrum disorder. Recently, copy-number variants of the nephronophthisis 1 gene have been reported in patients with autism spectrum disorder. To the best of our knowledge, only six autism spectrum disorder cases with duplications of the nephronophthisis 1 gene have been reported. These patients exhibited intellectual dysfunction, including verbal dysfunction in one patient, below-average verbal intellectual ability in one patient, and intellectual disability in four patients. In this study, we identified nephronophthisis 1 duplications in two unrelated Japanese patients with autism spectrum disorder using a high-resolution single-nucleotide polymorphism array. This report is the first to describe a nephronophthisis 1 duplication in an autism spectrum disorder patient with an average verbal intelligence quotient and an average performance intelligence quotient. However, the second autism spectrum disorder patient with a nephronophthisis 1 duplication had a below-average performance intelligence quotient. Neither patient exhibited physical dysfunction, motor developmental delay, or neurological abnormalities. This study supports the clinical observation of nephronophthisis 1 duplication in autism spectrum disorder cases and might contribute to our understanding of the clinical phenotype that arises from this duplication.

  8. Gene duplications circumvent trade-offs in enzyme function: Insect adaptation to toxic host plants.

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    Dalla, Safaa; Dobler, Susanne

    2016-12-01

    Herbivorous insects and their adaptations against plant toxins provide striking opportunities to investigate the genetic basis of traits involved in coevolutionary interactions. Target site insensitivity to cardenolides has evolved convergently across six orders of insects, involving identical substitutions in the Na,K-ATPase gene and repeated convergent gene duplications. The large milkweed bug, Oncopeltus fasciatus, has three copies of the Na,K-ATPase α-subunit gene that bear differing numbers of amino acid substitutions in the binding pocket for cardenolides. To analyze the effect of these substitutions on cardenolide resistance and to infer possible trade-offs in gene function, we expressed the cardenolide-sensitive Na,K-ATPase of Drosophila melanogaster in vitro and introduced four distinct combinations of substitutions observed in the three gene copies of O. fasciatus. With an increasing number of substitutions, the sensitivity of the Na,K-ATPase to a standard cardenolide decreased in a stepwise manner. At the same time, the enzyme's overall activity decreased significantly with increasing cardenolide resistance and only the least substituted mimic of the Na,K-ATPase α1C copy maintained activity similar to the wild-type enzyme. Our results suggest that the Na,K-ATPase copies in O. fasciatus have diverged in function, enabling specific adaptations to dietary cardenolides while maintaining the functionality of this critical ion carrier. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  9. Gene duplication and fragmentation in the zebra finch major histocompatibility complex

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    Burt David W

    2010-04-01

    Full Text Available Abstract Background Due to its high polymorphism and importance for disease resistance, the major histocompatibility complex (MHC has been an important focus of many vertebrate genome projects. Avian MHC organization is of particular interest because the chicken Gallus gallus, the avian species with the best characterized MHC, possesses a highly streamlined minimal essential MHC, which is linked to resistance against specific pathogens. It remains unclear the extent to which this organization describes the situation in other birds and whether it represents a derived or ancestral condition. The sequencing of the zebra finch Taeniopygia guttata genome, in combination with targeted bacterial artificial chromosome (BAC sequencing, has allowed us to characterize an MHC from a highly divergent and diverse avian lineage, the passerines. Results The zebra finch MHC exhibits a complex structure and history involving gene duplication and fragmentation. The zebra finch MHC includes multiple Class I and Class II genes, some of which appear to be pseudogenes, and spans a much more extensive genomic region than the chicken MHC, as evidenced by the presence of MHC genes on each of seven BACs spanning 739 kb. Cytogenetic (FISH evidence and the genome assembly itself place core MHC genes on as many as four chromosomes with TAP and Class I genes mapping to different chromosomes. MHC Class II regions are further characterized by high endogenous retroviral content. Lastly, we find strong evidence of selection acting on sites within passerine MHC Class I and Class II genes. Conclusion The zebra finch MHC differs markedly from that of the chicken, the only other bird species with a complete genome sequence. The apparent lack of synteny between TAP and the expressed MHC Class I locus is in fact reminiscent of a pattern seen in some mammalian lineages and may represent convergent evolution. Our analyses of the zebra finch MHC suggest a complex history involving

  10. 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

  11. Gene duplication and fragment recombination drive functional diversification of a superfamily of cytoplasmic effectors in Phytophthora sojae.

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    Shen, Danyu; Liu, Tingli; Ye, Wenwu; Liu, Li; Liu, Peihan; Wu, Yuren; Wang, Yuanchao; Dou, Daolong

    2013-01-01

    Phytophthora and other oomycetes secrete a large number of putative host cytoplasmic effectors with conserved FLAK motifs following signal peptides, termed crinkling and necrosis inducing proteins (CRN), or Crinkler. Here, we first investigated the evolutionary patterns and mechanisms of CRN effectors in Phytophthora sojae and compared them to two other Phytophthora species. The genes encoding CRN effectors could be divided into 45 orthologous gene groups (OGG), and most OGGs unequally distributed in the three species, in which each underwent large number of gene gains or losses, indicating that the CRN genes expanded after species evolution in Phytophthora and evolved through pathoadaptation. The 134 expanded genes in P. sojae encoded family proteins including 82 functional genes and expressed at higher levels while the other 68 genes encoding orphan proteins were less expressed and contained 50 pseudogenes. Furthermore, we demonstrated that most expanded genes underwent gene duplication or/and fragment recombination. Three different mechanisms that drove gene duplication or recombination were identified. Finally, the expanded CRN effectors exhibited varying pathogenic functions, including induction of programmed cell death (PCD) and suppression of PCD through PAMP-triggered immunity or/and effector-triggered immunity. Overall, these results suggest that gene duplication and fragment recombination may be two mechanisms that drive the expansion and neofunctionalization of the CRN family in P. sojae, which aids in understanding the roles of CRN effectors within each oomycete pathogen.

  12. Gene duplication and fragment recombination drive functional diversification of a superfamily of cytoplasmic effectors in Phytophthora sojae.

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    Danyu Shen

    Full Text Available Phytophthora and other oomycetes secrete a large number of putative host cytoplasmic effectors with conserved FLAK motifs following signal peptides, termed crinkling and necrosis inducing proteins (CRN, or Crinkler. Here, we first investigated the evolutionary patterns and mechanisms of CRN effectors in Phytophthora sojae and compared them to two other Phytophthora species. The genes encoding CRN effectors could be divided into 45 orthologous gene groups (OGG, and most OGGs unequally distributed in the three species, in which each underwent large number of gene gains or losses, indicating that the CRN genes expanded after species evolution in Phytophthora and evolved through pathoadaptation. The 134 expanded genes in P. sojae encoded family proteins including 82 functional genes and expressed at higher levels while the other 68 genes encoding orphan proteins were less expressed and contained 50 pseudogenes. Furthermore, we demonstrated that most expanded genes underwent gene duplication or/and fragment recombination. Three different mechanisms that drove gene duplication or recombination were identified. Finally, the expanded CRN effectors exhibited varying pathogenic functions, including induction of programmed cell death (PCD and suppression of PCD through PAMP-triggered immunity or/and effector-triggered immunity. Overall, these results suggest that gene duplication and fragment recombination may be two mechanisms that drive the expansion and neofunctionalization of the CRN family in P. sojae, which aids in understanding the roles of CRN effectors within each oomycete pathogen.

  13. Gene duplication, loss and selection in the evolution of saxitoxin biosynthesis in alveolates.

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    Murray, Shauna A; Diwan, Rutuja; Orr, Russell J S; Kohli, Gurjeet S; John, Uwe

    2015-11-01

    A group of marine dinoflagellates (Alveolata, Eukaryota), consisting of ∼10 species of the genus Alexandrium, Gymnodinium catenatum and Pyrodinium bahamense, produce the toxin saxitoxin and its analogues (STX), which can accumulate in shellfish, leading to ecosystem and human health impacts. The genes, sxt, putatively involved in STX biosynthesis, have recently been identified, however, the evolution of these genes within dinoflagellates is not clear. There are two reasons for this: uncertainty over the phylogeny of dinoflagellates; and that the sxt genes of many species of Alexandrium and other dinoflagellate genera are not known. Here, we determined the phylogeny of STX-producing and other dinoflagellates based on a concatenated eight-gene alignment. We determined the presence, diversity and phylogeny of sxtA, domains A1 and A4 and sxtG in 52 strains of Alexandrium, and a further 43 species of dinoflagellates and thirteen other alveolates. We confirmed the presence and high sequence conservation of sxtA, domain A4, in 40 strains (35 Alexandrium, 1 Pyrodinium, 4 Gymnodinium) of 8 species of STX-producing dinoflagellates, and absence from non-producing species. We found three paralogs of sxtA, domain A1, and a widespread distribution of sxtA1 in non-STX producing dinoflagellates, indicating duplication events in the evolution of this gene. One paralog, clade 2, of sxtA1 may be particularly related to STX biosynthesis. Similarly, sxtG appears to be generally restricted to STX-producing species, while three amidinotransferase gene paralogs were found in dinoflagellates. We investigated the role of positive (diversifying) selection following duplication in sxtA1 and sxtG, and found negative selection in clades of sxtG and sxtA1, clade 2, suggesting they were functionally constrained. Significant episodic diversifying selection was found in some strains in clade 3 of sxtA1, a clade that may not be involved in STX biosynthesis, indicating pressure for diversification

  14. Genome-wide analysis of homeobox genes from Mesobuthus martensii reveals Hox gene duplication in scorpions.

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    Di, Zhiyong; Yu, Yao; Wu, Yingliang; Hao, Pei; He, Yawen; Zhao, Huabin; Li, Yixue; Zhao, Guoping; Li, Xuan; Li, Wenxin; Cao, Zhijian

    2015-06-01

    Homeobox genes belong to a large gene group, which encodes the famous DNA-binding homeodomain that plays a key role in development and cellular differentiation during embryogenesis in animals. Here, one hundred forty-nine homeobox genes were identified from the Asian scorpion, Mesobuthus martensii (Chelicerata: Arachnida: Scorpiones: Buthidae) based on our newly assembled genome sequence with approximately 248 × coverage. The identified homeobox genes were categorized into eight classes including 82 families: 67 ANTP class genes, 33 PRD genes, 11 LIM genes, five POU genes, six SINE genes, 14 TALE genes, five CUT genes, two ZF genes and six unclassified genes. Transcriptome data confirmed that more than half of the genes were expressed in adults. The homeobox gene diversity of the eight classes is similar to the previously analyzed Mandibulata arthropods. Interestingly, it is hypothesized that the scorpion M. martensii may have two Hox clusters. The first complete genome-wide analysis of homeobox genes in Chelicerata not only reveals the repertoire of scorpion, arachnid and chelicerate homeobox genes, but also shows some insights into the evolution of arthropod homeobox genes.

  15. Tubulin evolution in insects: gene duplication and subfunctionalization provide specialized isoforms in a functionally constrained gene family

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    Gadagkar Sudhindra R

    2010-04-01

    Full Text Available Abstract Background The completion of 19 insect genome sequencing projects spanning six insect orders provides the opportunity to investigate the evolution of important gene families, here tubulins. Tubulins are a family of eukaryotic structural genes that form microtubules, fundamental components of the cytoskeleton that mediate cell division, shape, motility, and intracellular trafficking. Previous in vivo studies in Drosophila find a stringent relationship between tubulin structure and function; small, biochemically similar changes in the major alpha 1 or testis-specific beta 2 tubulin protein render each unable to generate a motile spermtail axoneme. This has evolutionary implications, not a single non-synonymous substitution is found in beta 2 among 17 species of Drosophila and Hirtodrosophila flies spanning 60 Myr of evolution. This raises an important question, How do tubulins evolve while maintaining their function? To answer, we use molecular evolutionary analyses to characterize the evolution of insect tubulins. Results Sixty-six alpha tubulins and eighty-six beta tubulin gene copies were retrieved and subjected to molecular evolutionary analyses. Four ancient clades of alpha and beta tubulins are found in insects, a major isoform clade (alpha 1, beta 1 and three minor, tissue-specific clades (alpha 2-4, beta 2-4. Based on a Homarus americanus (lobster outgroup, these were generated through gene duplication events on major beta and alpha tubulin ancestors, followed by subfunctionalization in expression domain. Strong purifying selection acts on all tubulins, yet maximum pairwise amino acid distances between tubulin paralogs are large (0.464 substitutions/site beta tubulins, 0.707 alpha tubulins. Conversely orthologs, with the exception of reproductive tissue isoforms, show little sequence variation except in the last 15 carboxy terminus tail (CTT residues, which serve as sites for post-translational modifications (PTMs and interactions

  16. Resolution and reconciliation of non-binary gene trees with transfers, duplications and losses.

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    Jacox, Edwin; Weller, Mathias; Tannier, Eric; Scornavacca, Celine

    2017-04-01

    Gene trees reconstructed from sequence alignments contain poorly supported branches when the phylogenetic signal in the sequences is insufficient to determine them all. When a species tree is available, the signal of gains and losses of genes can be used to correctly resolve the unsupported parts of the gene history. However finding a most parsimonious binary resolution of a non-binary tree obtained by contracting the unsupported branches is NP-hard if transfer events are considered as possible gene scale events, in addition to gene origination, duplication and loss. We propose an exact, parameterized algorithm to solve this problem in single-exponential time, where the parameter is the number of connected branches of the gene tree that show low support from the sequence alignment or, equivalently, the maximum number of children of any node of the gene tree once the low-support branches have been collapsed. This improves on the best known algorithm by an exponential factor. We propose a way to choose among optimal solutions based on the available information. We show the usability of this principle on several simulated and biological datasets. The results are comparable in quality to several other tested methods having similar goals, but our approach provides a lower running time and a guarantee that the produced solution is optimal. Our algorithm has been integrated into the ecceTERA phylogeny package, available at http://mbb.univ-montp2.fr/MBB/download_sources/16__ecceTERA and which can be run online at http://mbb.univ-montp2.fr/MBB/subsection/softExec.php?soft=eccetera . celine.scornavacca@umontpellier.fr. Supplementary data are available at Bioinformatics online.

  17. 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

    2016-01-05

    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.

  18. The major resistance gene cluster in lettuce is highly duplicated and spans several megabases.

    Science.gov (United States)

    Meyers, B C; Chin, D B; Shen, K A; Sivaramakrishnan, S; Lavelle, D O; Zhang, Z; Michelmore, R W

    1998-11-01

    At least 10 Dm genes conferring resistance to the oomycete downy mildew fungus Bremia lactucae map to the major resistance cluster in lettuce. We investigated the structure of this cluster in the lettuce cultivar Diana, which contains Dm3. A deletion breakpoint map of the chromosomal region flanking Dm3 was saturated with a variety of molecular markers. Several of these markers are components of a family of resistance gene candidates (RGC2) that encode a nucleotide binding site and a leucine-rich repeat region. These motifs are characteristic of plant disease resistance genes. Bacterial artificial chromosome clones were identified by using duplicated restriction fragment length polymorphism markers from the region, including the nucleotide binding site-encoding region of RGC2. Twenty-two distinct members of the RGC2 family were characterized from the bacterial artificial chromosomes; at least two additional family members exist. The RGC2 family is highly divergent; the nucleotide identity was as low as 53% between the most distantly related copies. These RGC2 genes span at least 3.5 Mb. Eighteen members were mapped on the deletion breakpoint map. A comparison between the phylogenetic and physical relationships of these sequences demonstrated that closely related copies are physically separated from one another and indicated that complex rearrangements have shaped this region. Analysis of low-copy genomic sequences detected no genes, including RGC2, in the Dm3 region, other than sequences related to retrotransposons and transposable elements. The related but divergent family of RGC2 genes may act as a resource for the generation of new resistance phenotypes through infrequent recombination or unequal crossing over.

  19. The opsin repertoire of Jenynsia onca: a new perspective on gene duplication and divergence in livebearers

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    Owens Gregory L

    2009-08-01

    Full Text Available Abstract Background Jenynsia onca, commonly known as the one sided livebearer, is a member of the family Anablepidae. The opsin gene repertoires of J. onca's close relatives, the four-eyed fish (Anableps anableps and the guppy (Poecilia reticulata, have been characterized and each found to include one unique LWS opsin. Currently, the relationship among LWS paralogs and orthologs in these species are unclear, making it difficult to test the hypotheses that link vision to morphology or life history traits. The phylogenetic signal appears to have been disrupted by gene conversion. Here we have sequenced the opsin genes of J. onca in order to resolve these relationships. Findings We identified nine visual opsins; LWS S180r, LWS S180, LWS P180, SWS1, SWS2A, SWS2B, RH1, RH2-1, and RH2-2. Key site analysis revealed only one unique haplotype, RH2-2, although this is unlikely to shift λmax significantly. LWS P180 was found to be a product of a gene conversion event with LWS S180, followed by convergence to a proline residue at the 180 site. Conclusion Jenynsia onca has at least 9 visual opsins: three LWS, one RH1, two RH2, one SWS1 and two SWS2. The presence of LWS P180 moves the location of the LWS P180-S180 tandem duplication event back to the base of the Poeciliidae-Anablepidae clade, expanding the number of species possessing this unusual blue shifted LWS opsin. The presence of the LWS P180 gene also confirms that gene conversion events have homogenized opsin paralogs in fish, just as they have in humans.

  20. Genome-wide analysis of the Dof transcription factor gene family reveals soybean-specific duplicable and functional characteristics.

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    Yong Guo

    Full Text Available The Dof domain protein family is a classic plant-specific zinc-finger transcription factor family involved in a variety of biological processes. There is great diversity in the number of Dof genes in different plants. However, there are only very limited reports on the characterization of Dof transcription factors in soybean (Glycine max. In the present study, 78 putative Dof genes were identified from the whole-genome sequence of soybean. The predicted GmDof genes were non-randomly distributed within and across 19 out of 20 chromosomes and 97.4% (38 pairs were preferentially retained duplicate paralogous genes located in duplicated regions of the genome. Soybean-specific segmental duplications contributed significantly to the expansion of the soybean Dof gene family. These Dof proteins were phylogenetically clustered into nine distinct subgroups among which the gene structure and motif compositions were considerably conserved. Comparative phylogenetic analysis of these Dof proteins revealed four major groups, similar to those reported for Arabidopsis and rice. Most of the GmDofs showed specific expression patterns based on RNA-seq data analyses. The expression patterns of some duplicate genes were partially redundant while others showed functional diversity, suggesting the occurrence of sub-functionalization during subsequent evolution. Comprehensive expression profile analysis also provided insights into the soybean-specific functional divergence among members of the Dof gene family. Cis-regulatory element analysis of these GmDof genes suggested diverse functions associated with different processes. Taken together, our results provide useful information for the functional characterization of soybean Dof genes by combining phylogenetic analysis with global gene-expression profiling.

  1. Identification of coding exon 3 duplication in the BMPR1A gene in a patient with juvenile polyposis syndrome.

    Science.gov (United States)

    Yamaguchi, Junya; Nagayama, Satoshi; Chino, Akiko; Sakata, Ai; Yamamoto, Noriko; Sato, Yuri; Ashihara, Yuumi; Kita, Mizuho; Nomura, Sachio; Ishikawa, Yuichi; Igarashi, Masahiro; Ueno, Masashi; Arai, Masami

    2014-10-01

    Juvenile polyposis syndrome is an autosomal dominant inherited disorder characterized by multiple juvenile polyps arising in the gastrointestinal tract and an increased risk of gastrointestinal cancers, specifically colon cancer. BMPR1A and SMAD4 germline mutations have been found in patients with juvenile polyposis syndrome. We identified a BMPR1A mutation, which involves a duplication of coding exon 3 (c.230+452_333+441dup1995), on multiple ligation dependent probe amplification in a patient with juvenile polyposis syndrome. The mutation causes a frameshift, producing a truncated protein (p.D112NfsX2). Therefore, the mutation is believed to be pathogenic. We also identified a duplication breakpoint in which Alu sequences are located. These results suggest that the duplication event resulted from recombination between Alu sequences. To our knowledge, partial duplication in the BMPR1A gene has not been reported previously. This is the first case report to document coding exon 3 duplication in the BMPR1A gene in a patient with juvenile polyposis syndrome.

  2. The evolution and maintenance of Hox gene clusters in vertebrates and the teleost-specific genome duplication.

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    Kuraku, Shigehiro; Meyer, Axel

    2009-01-01

    Hox genes are known to specify spatial identities along the anterior-posterior axis during embryogenesis. In vertebrates and most other deuterostomes, they are arranged in sets of uninterrupted clusters on chromosomes, and are in most cases expressed in a "colinear" fashion, in which genes closer to the 3-end of the Hox clusters are expressed earlier and more anteriorly and genes close to the 5-end of the clusters later and more posteriorly. In this review, we summarize the current understanding of how Hox gene clusters have been modified from basal lineages of deuterostomes to diverse taxa of vertebrates. Our parsimony reconstruction of Hox cluster architecture at various stages of vertebrate evolution highlights that the variation in Hox cluster structures among jawed vertebrates is mostly due to secondary lineage-specific gene losses and an additional genome duplication that occurred in the actinopterygian stem lineage, the teleost-specific genome duplication (TSGD).

  3. The role of gene duplication and unconstrained selective pressures in the melanopsin gene family evolution and vertebrate circadian rhythm regulation.

    Science.gov (United States)

    Borges, Rui; Johnson, Warren E; O'Brien, Stephen J; Vasconcelos, Vitor; Antunes, Agostinho

    2012-01-01

    Melanopsin is a photosensitive cell protein involved in regulating circadian rhythms and other non-visual responses to light. The melanopsin gene family is represented by two paralogs, OPN4x and OPN4m, which originated through gene duplication early in the emergence of vertebrates. Here we studied the melanopsin gene family using an integrated gene/protein evolutionary approach, which revealed that the rhabdomeric urbilaterian ancestor had the same amino acid patterns (DRY motif and the Y and E conterions) as extant vertebrate species, suggesting that the mechanism for light detection and regulation is similar to rhabdomeric rhodopsins. Both OPN4m and OPN4x paralogs are found in vertebrate genomic paralogons, suggesting that they diverged following this duplication event about 600 million years ago, when the complex eye emerged in the vertebrate ancestor. Melanopsins generally evolved under negative selection (ω = 0.171) with some minor episodes of positive selection (proportion of sites = 25%) and functional divergence (θ(I) = 0.349 and θ(II) = 0.126). The OPN4m and OPN4x melanopsin paralogs show evidence of spectral divergence at sites likely involved in melanopsin light absorbance (200F, 273S and 276A). Also, following the teleost lineage-specific whole genome duplication (3R) that prompted the teleost fish radiation, type I divergence (θ(I) = 0.181) and positive selection (affecting 11% of sites) contributed to amino acid variability that we related with the photo-activation stability of melanopsin. The melanopsin intracellular regions had unexpectedly high variability in their coupling specificity of G-proteins and we propose that Gq/11 and Gi/o are the two G-proteins most-likely to mediate the melanopsin phototransduction pathway. The selection signatures were mainly observed on retinal-related sites and the third and second intracellular loops, demonstrating the physiological plasticity of the melanopsin protein group. Our results provide new insights on

  4. The role of gene duplication and unconstrained selective pressures in the melanopsin gene family evolution and vertebrate circadian rhythm regulation.

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    Rui Borges

    Full Text Available Melanopsin is a photosensitive cell protein involved in regulating circadian rhythms and other non-visual responses to light. The melanopsin gene family is represented by two paralogs, OPN4x and OPN4m, which originated through gene duplication early in the emergence of vertebrates. Here we studied the melanopsin gene family using an integrated gene/protein evolutionary approach, which revealed that the rhabdomeric urbilaterian ancestor had the same amino acid patterns (DRY motif and the Y and E conterions as extant vertebrate species, suggesting that the mechanism for light detection and regulation is similar to rhabdomeric rhodopsins. Both OPN4m and OPN4x paralogs are found in vertebrate genomic paralogons, suggesting that they diverged following this duplication event about 600 million years ago, when the complex eye emerged in the vertebrate ancestor. Melanopsins generally evolved under negative selection (ω = 0.171 with some minor episodes of positive selection (proportion of sites = 25% and functional divergence (θ(I = 0.349 and θ(II = 0.126. The OPN4m and OPN4x melanopsin paralogs show evidence of spectral divergence at sites likely involved in melanopsin light absorbance (200F, 273S and 276A. Also, following the teleost lineage-specific whole genome duplication (3R that prompted the teleost fish radiation, type I divergence (θ(I = 0.181 and positive selection (affecting 11% of sites contributed to amino acid variability that we related with the photo-activation stability of melanopsin. The melanopsin intracellular regions had unexpectedly high variability in their coupling specificity of G-proteins and we propose that Gq/11 and Gi/o are the two G-proteins most-likely to mediate the melanopsin phototransduction pathway. The selection signatures were mainly observed on retinal-related sites and the third and second intracellular loops, demonstrating the physiological plasticity of the melanopsin protein group. Our results provide new

  5. Plant Genome Duplication Database.

    Science.gov (United States)

    Lee, Tae-Ho; Kim, Junah; Robertson, Jon S; Paterson, Andrew H

    2017-01-01

    Genome duplication, widespread in flowering plants, is a driving force in evolution. Genome alignments between/within genomes facilitate identification of homologous regions and individual genes to investigate evolutionary consequences of genome duplication. PGDD (the Plant Genome Duplication Database), a public web service database, provides intra- or interplant genome alignment information. At present, PGDD contains information for 47 plants whose genome sequences have been released. Here, we describe methods for identification and estimation of dates of genome duplication and speciation by functions of PGDD.The database is freely available at http://chibba.agtec.uga.edu/duplication/.

  6. Molecular Characterization of Duplicate Cytosolic Phosphoglucose Isomerase Genes in Clarkia and Comparison to the Single Gene in Arabidopsis

    Science.gov (United States)

    Thomas, B. R.; Ford, V. S.; Pichersky, E.; Gottlieb, L. D.

    1993-01-01

    The nucleotide sequence of PgiC1-a which encodes a cytosolic isozyme of phosphoglucose isomerase (PGIC; EC 5.3.1.9) in Clarkia lewisii, a wildflower native to California, is described and compared to the previously published sequence of the duplicate PgiC2-a from the same genome. Both genes have the same structure of 23 exons and 22 introns located in identical positions, and they encode proteins of 569 amino acids. Exon and inferred protein sequences of the two genes are 96.4% and 97.2% identical, respectively. Intron sequences are 88.2% identical. The high nucleotide similarity of the two genes is consistent with previous genetic and biosystematic findings that suggest the duplication arose within Clarkia. A partial sequence of PgiC2-b was also obtained. It is 99.5% identical to PgiC2-a in exons and 99.7% in introns. The nucleotide sequence of the single PgiC from Arabidopsis thaliana was also determined for comparison to the Clarkia genes. The A. thaliana PgiC has 21 introns located at positions identical to those in Clarkia PgiC1 and PgiC2, but lacks the intron that divides Clarkia exons 21 and 22. The A. thaliana PGIC protein is shorter, with 560 amino acids, and differs by about 17% from the Clarkia PGICs. The PgiC in A. thaliana was mapped to a site 20 cM from restriction fragment length polymorphism marker 331 on chromosome 5. PMID:8293986

  7. Allelic Polymorphism, Gene Duplication and Balancing Selection of MHC Class IIB Genes in the Omei Treefrog (Rhacophorus omeimontis)

    Institute of Scientific and Technical Information of China (English)

    Li HUANG; Mian ZHAO; Zhenhua LUO; Hua WU

    2016-01-01

    The worldwide declines in amphibian populations have largely been caused by infectious fungi and bacteria. Given that vertebrate immunity against these extracellular pathogens is primarily functioned by the major histocompatibility complex (MHC) class II molecules, the characterization and the evolution of amphibian MHC class II genes have attracted increasing attention. The polymorphism of MHC class II genes was found to be correlated with susceptibility to fungal pathogens in many amphibian species, suggesting the importance of studies on MHC class II genes for amphibians. However, such studies on MHC class II gene evolution have rarely been conducted on amphibians in China. In this study, we chose Omei treefrog (Rhacophorus omeimontis), which lived moist environments easy for breeding bacteria, to study the polymorphism of its MHC class II genes and the underlying evolutionary mechanisms. We amplified the entire MHC class IIB exon 2 sequence in the R. omeimontis using newly designed primers. We detected 102 putative alleles in 146 individuals. The number of alleles per individual ranged from one to seven, indicating that there are at least four loci containing MHC class IIB genes in R. omeimontis. The allelic polymorphism estimated from the 102 alleles in R. omeimontis was not high compared to that estimated in other anuran species. No significant gene recombination was detected in the 102 MHC class IIB exon 2 sequences. In contrast, both gene duplication and balancing selection greatly contributed to the variability in MHC class IIB exon 2 sequences of R. omeimontis. This study lays the groundwork for the future researches to comprehensively analyze the evolution of amphibian MHC genes and to assess the role of MHC gene polymorphisms in resistance against extracellular pathogens for amphibians in China.

  8. Whole-genome duplications spurred the functional diversification of the globin gene superfamily in vertebrates.

    Science.gov (United States)

    Hoffmann, Federico G; Opazo, Juan C; Storz, Jay F

    2012-01-01

    It has been hypothesized that two successive rounds of whole-genome duplication (WGD) in the stem lineage of vertebrates provided genetic raw materials for the evolutionary innovation of many vertebrate-specific features. However, it has seldom been possible to trace such innovations to specific functional differences between paralogous gene products that derive from a WGD event. Here, we report genomic evidence for a direct link between WGD and key physiological innovations in the vertebrate oxygen transport system. Specifically, we demonstrate that key globin proteins that evolved specialized functions in different aspects of oxidative metabolism (hemoglobin, myoglobin, and cytoglobin) represent paralogous products of two WGD events in the vertebrate common ancestor. Analysis of conserved macrosynteny between the genomes of vertebrates and amphioxus (subphylum Cephalochordata) revealed that homologous chromosomal segments defined by myoglobin + globin-E, cytoglobin, and the α-globin gene cluster each descend from the same linkage group in the reconstructed proto-karyotype of the chordate common ancestor. The physiological division of labor between the oxygen transport function of hemoglobin and the oxygen storage function of myoglobin played a pivotal role in the evolution of aerobic energy metabolism, supporting the hypothesis that WGDs helped fuel key innovations in vertebrate evolution.

  9. Duplications of the neuropeptide receptor gene VIPR2 confer significant risk for schizophrenia.

    LENUS (Irish Health Repository)

    Vacic, Vladimir

    2011-03-24

    Rare copy number variants (CNVs) have a prominent role in the aetiology of schizophrenia and other neuropsychiatric disorders. Substantial risk for schizophrenia is conferred by large (>500-kilobase) CNVs at several loci, including microdeletions at 1q21.1 (ref. 2), 3q29 (ref. 3), 15q13.3 (ref. 2) and 22q11.2 (ref. 4) and microduplication at 16p11.2 (ref. 5). However, these CNVs collectively account for a small fraction (2-4%) of cases, and the relevant genes and neurobiological mechanisms are not well understood. Here we performed a large two-stage genome-wide scan of rare CNVs and report the significant association of copy number gains at chromosome 7q36.3 with schizophrenia. Microduplications with variable breakpoints occurred within a 362-kilobase region and were detected in 29 of 8,290 (0.35%) patients versus 2 of 7,431 (0.03%) controls in the combined sample. All duplications overlapped or were located within 89 kilobases upstream of the vasoactive intestinal peptide receptor gene VIPR2. VIPR2 transcription and cyclic-AMP signalling were significantly increased in cultured lymphocytes from patients with microduplications of 7q36.3. These findings implicate altered vasoactive intestinal peptide signalling in the pathogenesis of schizophrenia and indicate the VPAC2 receptor as a potential target for the development of new antipsychotic drugs.

  10. Mirror-image duplication of the primary axis and heart in Xenopus embryos by the overexpression of Msx-1 gene.

    Science.gov (United States)

    Chen, Y; Solursh, M

    1995-10-01

    The Msx-1 gene (formerly known as Hox-7) is a member of a discrete subclass of homeobox-containing genes. Examination of the expression pattern of Msx-1 in murine and avian embryos suggests that this gene may be involved in the regionalization of the medio-lateral axis during earlier development. We have examined the possible functions of Xenopus Msx-1 during early Xenopus embryonic development by overexpression of the Msx-1 gene. Overexpression of Msx-1 causes a left-right mirror-image duplication of primary axial structures, including notochord, neural tube, somites, suckers, and foregut. The embryonic developing heart is also mirror-image duplicated, including looping directions and polarity. These results indicate that Msx-1 may be involved in the mesoderm formation as well as left-right patterning in the early Xenopus embryonic development.

  11. Evolution of Vertebrate Adam Genes; Duplication of Testicular Adams from Ancient Adam9/9-like Loci.

    Science.gov (United States)

    Bahudhanapati, Harinath; Bhattacharya, Shashwati; Wei, Shuo

    2015-01-01

    Members of the disintegrin metalloproteinase (ADAM) family have important functions in regulating cell-cell and cell-matrix interactions as well as cell signaling. There are two major types of ADAMs: the somatic ADAMs (sADAMs) that have a significant presence in somatic tissues, and the testicular ADAMs (tADAMs) that are expressed predominantly in the testis. Genes encoding tADAMs can be further divided into two groups: group I (intronless) and group II (intron-containing). To date, tAdams have only been reported in placental mammals, and their evolutionary origin and relationship to sAdams remain largely unknown. Using phylogenetic and syntenic tools, we analyzed the Adam genes in various vertebrates ranging from fishes to placental mammals. Our analyses reveal duplication and loss of some sAdams in certain vertebrate species. In particular, there exists an Adam9-like gene in non-mammalian vertebrates but not mammals. We also identified putative group I and group II tAdams in all amniote species that have been examined. These tAdam homologues are more closely related to Adams 9 and 9-like than to other sAdams. In all amniote species examined, group II tAdams lie in close vicinity to Adam9 and hence likely arose from tandem duplication, whereas group I tAdams likely originated through retroposition because of their lack of introns. Clusters of multiple group I tAdams are also common, suggesting tandem duplication after retroposition. Therefore, Adam9/9-like and some of the derived tAdam loci are likely preferred targets for tandem duplication and/or retroposition. Consistent with this hypothesis, we identified a young retroposed gene that duplicated recently from Adam9 in the opossum. As a result of gene duplication, some tAdams were pseudogenized in certain species, whereas others acquired new expression patterns and functions. The rapid duplication of Adam genes has a major contribution to the diversity of ADAMs in various vertebrate species.

  12. Function of Partially Duplicated Human α7 Nicotinic Receptor Subunit CHRFAM7A Gene

    Science.gov (United States)

    de Lucas-Cerrillo, Ana M.; Maldifassi, M. Constanza; Arnalich, Francisco; Renart, Jaime; Atienza, Gema; Serantes, Rocío; Cruces, Jesús; Sánchez-Pacheco, Aurora; Andrés-Mateos, Eva; Montiel, Carmen

    2011-01-01

    The neuronal α7 nicotinic receptor subunit gene (CHRNA7) is partially duplicated in the human genome forming a hybrid gene (CHRFAM7A) with the novel FAM7A gene. The hybrid gene transcript, dupα7, has been identified in brain, immune cells, and the HL-60 cell line, although its translation and function are still unknown. In this study, dupα7 cDNA has been cloned and expressed in GH4C1 cells and Xenopus oocytes to study the pattern and functional role of the expressed protein. Our results reveal that dupα7 transcript was natively translated in HL-60 cells and heterologously expressed in GH4C1 cells and oocytes. Injection of dupα7 mRNA into oocytes failed to generate functional receptors, but when co-injected with α7 mRNA at α7/dupα7 ratios of 5:1, 2:1, 1:1, 1:5, and 1:10, it reduced the nicotine-elicited α7 current generated in control oocytes (α7 alone) by 26, 53, 75, 93, and 94%, respectively. This effect is mainly due to a reduction in the number of functional α7 receptors reaching the oocyte membrane, as deduced from α-bungarotoxin binding and fluorescent confocal assays. Two additional findings open the possibility that the dominant negative effect of dupα7 on α7 receptor activity observed in vitro could be extrapolated to in vivo situations. (i) Compared with α7 mRNA, basal dupα7 mRNA levels are substantial in human cerebral cortex and higher in macrophages. (ii) dupα7 mRNA levels in macrophages are down-regulated by IL-1β, LPS, and nicotine. Thus, dupα7 could modulate α7 receptor-mediated synaptic transmission and cholinergic anti-inflammatory response. PMID:21047781

  13. The fate of tandemly duplicated genes assessed by the expression analysis of a group of Arabidopsis thaliana RING-H2 ubiquitin ligase genes of the ATL family.

    Science.gov (United States)

    Aguilar-Hernández, Victor; Guzmán, Plinio

    2014-03-01

    Gene duplication events exert key functions on gene innovations during the evolution of the eukaryotic genomes. A large portion of the total gene content in plants arose from tandem duplications events, which often result in paralog genes with high sequence identity. Ubiquitin ligases or E3 enzymes are components of the ubiquitin proteasome system that function during the transfer of the ubiquitin molecule to the substrate. In plants, several E3s have expanded in their genomes as multigene families. To gain insight into the consequences of gene duplications on the expansion and diversification of E3s, we examined the evolutionary basis of a cluster of six genes, duplC-ATLs, which arose from segmental and tandem duplication events in Brassicaceae. The assessment of the expression suggested two patterns that are supported by lineage. While retention of expression domains was observed, an apparent absence or reduction of expression was also inferred. We found that two duplC-ATL genes underwent pseudogenization and that, in one case, gene expression is probably regained. Our findings provide insights into the evolution of gene families in plants, defining key events on the expansion of the Arabidopsis Tóxicos en Levadura family of E3 ligases.

  14. Genesis of the vertebrate FoxP subfamily member genes occurred during two ancestral whole genome duplication events.

    Science.gov (United States)

    Song, Xiaowei; Tang, Yezhong; Wang, Yajun

    2016-08-22

    The vertebrate FoxP subfamily genes play important roles in the construction of essential functional modules involved in physiological and developmental processes. To explore the adaptive evolution of functional modules associated with the FoxP subfamily member genes, it is necessary to study the gene duplication process. We detected four member genes of the FoxP subfamily in sea lampreys (a representative species of jawless vertebrates) through genome screenings and phylogenetic analyses. Reliable paralogons (i.e. paralogous chromosome segments) have rarely been detected in scaffolds of FoxP subfamily member genes in sea lampreys due to the considerable existence of HTH_Tnp_Tc3_2 transposases. However, these transposases did not alter gene numbers of the FoxP subfamily in sea lampreys. The coincidence between the "1-4" gene duplication pattern of FoxP subfamily genes from invertebrates to vertebrates and two rounds of ancestral whole genome duplication (1R- and 2R-WGD) events reveal that the FoxP subfamily of vertebrates was quadruplicated in the 1R- and 2R-WGD events. Furthermore, we deduced that a synchronous gene duplication process occurred for the FoxP subfamily and for three linked gene families/subfamilies (i.e. MIT family, mGluR group III and PLXNA subfamily) in the 1R- and 2R-WGD events using phylogenetic analyses and mirror-dendrogram methods (i.e. algorithms to test protein-protein interactions). Specifically, the ancestor of FoxP1 and FoxP3 and the ancestor of FoxP2 and FoxP4 were generated in 1R-WGD event. In the subsequent 2R-WGD event, these two ancestral genes were changed into FoxP1, FoxP2, FoxP3 and FoxP4. The elucidation of these gene duplication processes shed light on the phylogenetic relationships between functional modules of the FoxP subfamily member genes.

  15. Closely linked H2B genes in the marine copepod, Tigriopus californicus indicate a recent gene duplication or gene conversion event.

    Science.gov (United States)

    Brown, D; Cook, A; Wagner, M; Wells, D

    1992-01-01

    Two nonallelic histone gene clusters were characterized in the marine copepod, Tigriopus californicus. The DNA sequence of one of the clusters reveals six genes in the contiguous arrangement of H2B, H1, H3, H4, H2B and H2A. The order of genes within the second cluster is H3, H4, H2B and H2A. There is no evidence for the presence of an H1 gene in this cluster. Comparison of the three copepod H2B genes reveals a high degree of similarity between the 5' upstream regions and between the amino terminal halves of the two H2B genes found within the same cluster. From these data we infer that gene duplication and/or gene conversion events occurred within this cluster in the recent past.

  16. Duplication of the dystroglycan gene in most branches of teleost fish

    Directory of Open Access Journals (Sweden)

    Giardina Bruno

    2007-05-01

    Full Text Available Abstract Background The dystroglycan (DG complex is a major non-integrin cell adhesion system whose multiple biological roles involve, among others, skeletal muscle stability, embryonic development and synapse maturation. DG is composed of two subunits: α-DG, extracellular and highly glycosylated, and the transmembrane β-DG, linking the cytoskeleton to the surrounding basement membrane in a wide variety of tissues. A single copy of the DG gene (DAG1 has been identified so far in humans and other mammals, encoding for a precursor protein which is post-translationally cleaved to liberate the two DG subunits. Similarly, D. rerio (zebrafish seems to have a single copy of DAG1, whose removal was shown to cause a severe dystrophic phenotype in adult animals, although it is known that during evolution, due to a whole genome duplication (WGD event, many teleost fish acquired multiple copies of several genes (paralogues. Results Data mining of pufferfish (T. nigroviridis and T. rubripes and other teleost fish (O. latipes and G. aculeatus available nucleotide sequences revealed the presence of two functional paralogous DG sequences. RT-PCR analysis proved that both the DG sequences are transcribed in T. nigroviridis. One of the two DG sequences harbours an additional mini-intronic sequence, 137 bp long, interrupting the uncomplicated exon-intron-exon pattern displayed by DAG1 in mammals and D. rerio. A similar scenario emerged also in D. labrax (sea bass, from whose genome we have cloned and sequenced a new DG sequence that also harbours a shorter additional intronic sequence of 116 bp. Western blot analysis confirmed the presence of DG protein products in all the species analysed including two teleost Antarctic species (T. bernacchii and C. hamatus. Conclusion Our evolutionary analysis has shown that the whole-genome duplication event in the Class Actinopterygii (ray-finned fish involved also DAG1. We unravelled new important molecular genetic details

  17. Biological Consequences of Ancient Gene Acquisition and Duplication in the Large Genome of Candidatus Solibacter usitatus Ellin6076

    Energy Technology Data Exchange (ETDEWEB)

    Challacombe, Jean F [ORNL; Eichorst, Stephanie A [Los Alamos National Laboratory (LANL); Hauser, Loren John [ORNL; Land, Miriam L [ORNL; Xie, Gary [Los Alamos National Laboratory (LANL); Kuske, Cheryl R [Los Alamos National Laboratory (LANL)

    2011-01-01

    Members of the bacterial phylum Acidobacteria are widespread in soils and sediments worldwide, and are abundant in many soils. Acidobacteria are challenging to culture in vitro, and many basic features of their biology and functional roles in the soil have not been determined. Candidatus Solibacter usitatus strain Ellin6076 has a 9.9 Mb genome that is approximately 2 5 times as large as the other sequenced Acidobacteria genomes. Bacterial genome sizes typically range from 0.5 to 10 Mb and are influenced by gene duplication, horizontal gene transfer, gene loss and other evolutionary processes. Our comparative genome analyses indicate that the Ellin6076 large genome has arisen by horizontal gene transfer via ancient bacteriophage and/or plasmid-mediated transduction, and widespread small-scale gene duplications, resulting in an increased number of paralogs. Low amino acid sequence identities among functional group members, and lack of conserved gene order and orientation in regions containing similar groups of paralogs, suggest that most of the paralogs are not the result of recent duplication events. The genome sizes of additional cultured Acidobacteria strains were estimated using pulsed-field gel electrophoresis to determine the prevalence of the large genome trait within the phylum. Members of subdivision 3 had larger genomes than those of subdivision 1, but none were as large as the Ellin6076 genome. The large genome of Ellin6076 may not be typical of the phylum, and encodes traits that could provide a selective metabolic, defensive and regulatory advantage in the soil environment.

  18. Biological consequences of ancient gene acquisition and duplication in the large genome soil bacterium, ""solibacter usitatus"" strain Ellin6076

    Energy Technology Data Exchange (ETDEWEB)

    Challacombe, Jean F [Los Alamos National Laboratory; Eichorst, Stephanie A [Los Alamos National Laboratory; Xie, Gary [Los Alamos National Laboratory; Kuske, Cheryl R [Los Alamos National Laboratory; Hauser, Loren [ORNL; Land, Miriam [ORNL

    2009-01-01

    Bacterial genome sizes range from ca. 0.5 to 10Mb and are influenced by gene duplication, horizontal gene transfer, gene loss and other evolutionary processes. Sequenced genomes of strains in the phylum Acidobacteria revealed that 'Solibacter usistatus' strain Ellin6076 harbors a 9.9 Mb genome. This large genome appears to have arisen by horizontal gene transfer via ancient bacteriophage and plasmid-mediated transduction, as well as widespread small-scale gene duplications. This has resulted in an increased number of paralogs that are potentially ecologically important (ecoparalogs). Low amino acid sequence identities among functional group members and lack of conserved gene order and orientation in the regions containing similar groups of paralogs suggest that most of the paralogs were not the result of recent duplication events. The genome sizes of cultured subdivision 1 and 3 strains in the phylum Acidobacteria were estimated using pulsed-field gel electrophoresis to determine the prevalence of the large genome trait within the phylum. Members of subdivision 1 were estimated to have smaller genome sizes ranging from ca. 2.0 to 4.8 Mb, whereas members of subdivision 3 had slightly larger genomes, from ca. 5.8 to 9.9 Mb. It is hypothesized that the large genome of strain Ellin6076 encodes traits that provide a selective metabolic, defensive and regulatory advantage in the variable soil environment.

  19. Voltage-gated sodium channel gene repertoire of lampreys: gene duplications, tissue-specific expression and discovery of a long-lost gene.

    Science.gov (United States)

    Zakon, Harold H; Li, Weiming; Pillai, Nisha E; Tohari, Sumanty; Shingate, Prashant; Ren, Jianfeng; Venkatesh, Byrappa

    2017-09-27

    Studies of the voltage-gated sodium (Nav) channels of extant gnathostomes have made it possible to deduce that ancestral gnathostomes possessed four voltage-gated sodium channel genes derived from a single ancestral chordate gene following two rounds of genome duplication early in vertebrates. We investigated the Nav gene family in two species of lampreys (the Japanese lamprey Lethenteron japonicum and sea lamprey Petromyzon marinus) (jawless vertebrates-agnatha) and compared them with those of basal vertebrates to better understand the origin of Nav genes in vertebrates. We noted six Nav genes in both lamprey species, but orthology with gnathostome (jawed vertebrate) channels was inconclusive. Surprisingly, the Nav2 gene, ubiquitously found in invertebrates and believed to have been lost in vertebrates, is present in lampreys, elephant shark (Callorhinchus milii) and coelacanth (Latimeria chalumnae). Despite repeated duplication of the Nav1 family in vertebrates, Nav2 is only in single copy in those vertebrates in which it is retained, and was independently lost in ray-finned fishes and tetrapods. Of the other five Nav channel genes, most were expressed in brain, one in brain and heart, and one exclusively in skeletal muscle. Invertebrates do not express Nav channel genes in muscle. Thus, early in the vertebrate lineage Nav channels began to diversify and different genes began to express in heart and muscle. © 2017 The Author(s).

  20. North Carolina macular dystrophy (MCDR1) caused by a novel tandem duplication of the PRDM13 gene

    Science.gov (United States)

    Sullivan, Lori S.; Wheaton, Dianna K.; Locke, Kirsten G.; Jones, Kaylie D.; Koboldt, Daniel C.; Fulton, Robert S.; Wilson, Richard K.; Blanton, Susan H.; Birch, David G.; Daiger, Stephen P.

    2016-01-01

    Purpose To identify the underlying cause of disease in a large family with North Carolina macular dystrophy (NCMD). Methods A large four-generation family (RFS355) with an autosomal dominant form of NCMD was ascertained. Family members underwent comprehensive visual function evaluations. Blood or saliva from six affected family members and three unaffected spouses was collected and DNA tested for linkage to the MCDR1 locus on chromosome 6q12. Three affected family members and two unaffected spouses underwent whole exome sequencing (WES) and subsequently, custom capture of the linkage region followed by next-generation sequencing (NGS). Standard PCR and dideoxy sequencing were used to further characterize the mutation. Results Of the 12 eyes examined in six affected individuals, all but two had Gass grade 3 macular degeneration features. Large central excavation of the retinal and choroid layers, referred to as a macular caldera, was seen in an age-independent manner in the grade 3 eyes. The calderas are unique to affected individuals with MCDR1. Genome-wide linkage mapping and haplotype analysis of markers from the chromosome 6q region were consistent with linkage to the MCDR1 locus. Whole exome sequencing and custom-capture NGS failed to reveal any rare coding variants segregating with the phenotype. Analysis of the custom-capture NGS sequencing data for copy number variants uncovered a tandem duplication of approximately 60 kb on chromosome 6q. This region contains two genes, CCNC and PRDM13. The duplication creates a partial copy of CCNC and a complete copy of PRDM13. The duplication was found in all affected members of the family and is not present in any unaffected members. The duplication was not seen in 200 ethnically matched normal chromosomes. Conclusions The cause of disease in the original family with MCDR1 and several others has been recently reported to be dysregulation of the PRDM13 gene, caused by either single base substitutions in a DNase 1

  1. Ancestral gene duplication enabled the evolution of multifunctional cellulases in stick insects (Phasmatodea).

    Science.gov (United States)

    Shelomi, Matan; Heckel, David G; Pauchet, Yannick

    2016-04-01

    The Phasmatodea (stick insects) have multiple, endogenous, highly expressed copies of glycoside hydrolase family 9 (GH9) genes. The purpose for retaining so many was unknown. We cloned and expressed the enzymes in transfected insect cell lines, and tested the individual proteins against different plant cell wall component poly- and oligosaccharides. Nearly all isolated enzymes were active against carboxymethylcellulose, however most could also degrade glucomannan, and some also either xylan or xyloglucan. The latter two enzyme groups were each monophyletic, suggesting the evolution of these novel substrate specificities in an early ancestor of the order. Such enzymes are highly unusual for Metazoa, for which no xyloglucanases had been reported. Phasmatodea gut extracts could degrade multiple plant cell wall components fully into sugar monomers, suggesting that enzymatic breakdown of plant cell walls by the entire Phasmatodea digestome may contribute to the Phasmatodea nutritional budget. The duplication and neofunctionalization of GH9s in the ancestral Phasmatodea may have enabled them to specialize as folivores and diverge from their omnivorous ancestors. The structural changes enabling these unprecedented activities in the cellulases require further study.

  2. Probing the evolution of biological nitrogen fixation by examining phylogenetic relationships of nitrogen fixation genes related by gene duplication

    Science.gov (United States)

    Peters, J.; Boyd, E. S.; Hamilton, T.

    2011-12-01

    Mounting evidence indicates the presence of a near complete biological nitrogen cycle in redox stratified oceans during the late Archean to early Proterozoic (~2.5 to 2.0 Ga). It has been suggested that the iron (Fe)-only or vanadium (V)-dependent alternative forms of nitrogenase rather than molybdenum (Mo)-dependent form was responsible for dinitrogen (N2) fixation during this time because oceans were depleted in Mo and rich in Fe. However, the only extant nitrogen fixing organisms that harbor alternative nitrogenases also harbor a Mo-dependent nitrogenase. Furthermore, our recent global gene expression analysis revealed that the alternative enzymes rely on genes encoding biosynthetic machinery to assemble active enzymes that are associated with the Mo-dependent nitrogenase. In our recent work we conducted an in-depth phylogenetic analysis of the proteins required for molybdenum (Mo)-nitrogenase that arose from gene fusion and duplication, expanding on previous analyses of single gene loci and multiple gene loci. The results of this analysis are highly suggestive that Mo-nitrogenase is unlikely to have been associated with the last universal common ancestor (LUCA). Rather, the oldest extant organisms harboring Mo-nitrogenase can be traced to hydrogenotrophic methanogens with acquisition in the bacterial domain via lateral gene transfer involving an anaerobic member of the Firmicutes. An origin and ensuing proliferation of Mo-nitrogenase under anoxic conditions would likely have occurred in an environment where anaerobic methanogens and Firmicutes coexisted and where Mo was at least episodically available, such as in a redox stratified Proterozoic ocean basin. In more recent work we have examined the hypothesis that the alternative forms predate the Mo-dependent nitrogenase by examining the phylogenetic relationships of the genetically distinct structural proteins of the Fe-only, V-, and Mo-nitrogenase that are required for activity. As a result, a clear and

  3. New insights into the nutritional regulation of gluconeogenesis in carnivorous rainbow trout (Oncorhynchus mykiss): a gene duplication trail.

    Science.gov (United States)

    Marandel, Lucie; Seiliez, Iban; Véron, Vincent; Skiba-Cassy, Sandrine; Panserat, Stéphane

    2015-07-01

    The rainbow trout (Oncorhynchus mykiss) is considered to be a strictly carnivorous fish species that is metabolically adapted for high catabolism of proteins and low utilization of dietary carbohydrates. This species consequently has a "glucose-intolerant" phenotype manifested by persistent hyperglycemia when fed a high-carbohydrate diet. Gluconeogenesis in adult fish is also poorly, if ever, regulated by carbohydrates, suggesting that this metabolic pathway is involved in this specific phenotype. In this study, we hypothesized that the fate of duplicated genes after the salmonid-specific 4th whole genome duplication (Ss4R) may have led to adaptive innovation and that their study might provide new elements to enhance our understanding of gluconeogenesis and poor dietary carbohydrate use in this species. Our evolutionary analysis of gluconeogenic genes revealed that pck1, pck2, fbp1a, and g6pca were retained as singletons after Ss4r, while g6pcb1, g6pcb2, and fbp1b ohnolog pairs were maintained. For all genes, duplication may have led to sub- or neofunctionalization. Expression profiles suggest that the gluconeogenesis pathway remained active in trout fed a no-carbohydrate diet. When trout were fed a high-carbohydrate diet (30%), most of the gluconeogenic genes were non- or downregulated, except for g6pbc2 ohnologs, whose RNA levels were surprisingly increased. This study demonstrates that Ss4R in trout involved adaptive innovation via gene duplication and via the outcome of the resulting ohnologs. Indeed, maintenance of ohnologous g6pcb2 pair may contribute in a significant way to the glucose-intolerant phenotype of trout and may partially explain its poor use of dietary carbohydrates.

  4. Reconciling gene and genome duplication events: using multiple nuclear gene families to infer the phylogeny of the aquatic plant family Pontederiaceae.

    Science.gov (United States)

    Ness, Rob W; Graham, Sean W; Barrett, Spencer C H

    2011-11-01

    Most plant phylogenetic inference has used DNA sequence data from the plastid genome. This genome represents a single genealogical sample with no recombination among genes, potentially limiting the resolution of evolutionary relationships in some contexts. In contrast, nuclear DNA is inherently more difficult to employ for phylogeny reconstruction because major mutational events in the genome, including polyploidization, gene duplication, and gene extinction can result in homologous gene copies that are difficult to identify as orthologs or paralogs. Gene tree parsimony (GTP) can be used to infer the rooted species tree by fitting gene genealogies to species trees while simultaneously minimizing the estimated number of duplications needed to reconcile conflicts among them. Here, we use GTP for five nuclear gene families and a previously published plastid data set to reconstruct the phylogenetic backbone of the aquatic plant family Pontederiaceae. Plastid-based phylogenetic studies strongly supported extensive paraphyly of Eichhornia (one of the four major genera) but also depicted considerable ambiguity concerning the true root placement for the family. Our results indicate that species trees inferred from the nuclear genes (alone and in combination with the plastid data) are highly congruent with gene trees inferred from plastid data alone. Consideration of optimal and suboptimal gene tree reconciliations place the root of the family at (or near) a branch leading to the rare and locally restricted E. meyeri. We also explore methods to incorporate uncertainty in individual gene trees during reconciliation by considering their individual bootstrap profiles and relate inferred excesses of gene duplication events on individual branches to whole-genome duplication events inferred for the same branches. Our study improves understanding of the phylogenetic history of Pontederiaceae and also demonstrates the utility of GTP for phylogenetic analysis.

  5. Evolution of CONSTANS Regulation and Function after Gene Duplication Produced a Photoperiodic Flowering Switch in the Brassicaceae.

    Science.gov (United States)

    Simon, Samson; Rühl, Mark; de Montaigu, Amaury; Wötzel, Stefan; Coupland, George

    2015-09-01

    Environmental control of flowering allows plant reproduction to occur under optimal conditions and facilitates adaptation to different locations. At high latitude, flowering of many plants is controlled by seasonal changes in day length. The photoperiodic flowering pathway confers this response in the Brassicaceae, which colonized temperate latitudes after divergence from the Cleomaceae, their subtropical sister family. The CONSTANS (CO) transcription factor of Arabidopsis thaliana, a member of the Brassicaceae, is central to the photoperiodic flowering response and shows characteristic patterns of transcription required for day-length sensing. CO is believed to be widely conserved among flowering plants; however, we show that it arose after gene duplication at the root of the Brassicaceae followed by divergence of transcriptional regulation and protein function. CO has two close homologs, CONSTANS-LIKE1 (COL1) and COL2, which are related to CO by tandem duplication and whole-genome duplication, respectively. The single CO homolog present in the Cleomaceae shows transcriptional and functional features similar to those of COL1 and COL2, suggesting that these were ancestral. We detect cis-regulatory and codon changes characteristic of CO and use transgenic assays to demonstrate their significance in the day-length-dependent activation of the CO target gene FLOWERING LOCUS T. Thus, the function of CO as a potent photoperiodic flowering switch evolved in the Brassicaceae after gene duplication. The origin of CO may have contributed to the range expansion of the Brassicaceae and suggests that in other families CO genes involved in photoperiodic flowering arose by convergent evolution.

  6. Chaperonin genes on the rise: new divergent classes and intense duplication in human and other vertebrate genomes

    Directory of Open Access Journals (Sweden)

    Macario Alberto JL

    2010-03-01

    Full Text Available Abstract Background Chaperonin proteins are well known for the critical role they play in protein folding and in disease. However, the recent identification of three diverged chaperonin paralogs associated with the human Bardet-Biedl and McKusick-Kaufman Syndromes (BBS and MKKS, respectively indicates that the eukaryotic chaperonin-gene family is larger and more differentiated than previously thought. The availability of complete genome sequences makes possible a definitive characterization of the complete set of chaperonin sequences in human and other species. Results We identified fifty-four chaperonin-like sequences in the human genome and similar numbers in the genomes of the model organisms mouse and rat. In mammal genomes we identified, besides the well-known CCT chaperonin genes and the three genes associated with the MKKS and BBS pathological conditions, a newly-defined class of chaperonin genes named CCT8L, represented in human by the two sequences CCT8L1 and CCT8L2. Comparative analyses from several vertebrate genomes established the monophyletic origin of chaperonin-like MKKS and BBS genes from the CCT8 lineage. The CCT8L gene originated from a later duplication also in the CCT8 lineage at the onset of mammal evolution and duplicated in primate genomes. The functionality of CCT8L genes in different species was confirmed by evolutionary analyses and in human by expression data. Detailed sequence analysis and structural predictions of MKKS, BBS and CCT8L proteins strongly suggested that they conserve a typical chaperonin-like core structure but that they are unlikely to form a CCT-like oligomeric complex. The characterization of many newly-discovered chaperonin pseudogenes uncovered the intense duplication activity of eukaryotic chaperonin genes. Conclusions In vertebrates, chaperonin genes, driven by intense duplication processes, have diversified into multiple classes and functionalities that extend beyond their well-known protein

  7. Tandem Duplication Events in the Expansion of the Small Heat Shock Protein Gene Family in Solanum lycopersicum (cv. Heinz 1706)

    Science.gov (United States)

    Krsticevic, Flavia J.; Arce, Débora P.; Ezpeleta, Joaquín; Tapia, Elizabeth

    2016-01-01

    In plants, fruit maturation and oxidative stress can induce small heat shock protein (sHSP) synthesis to maintain cellular homeostasis. Although the tomato reference genome was published in 2012, the actual number and functionality of sHSP genes remain unknown. Using a transcriptomic (RNA-seq) and evolutionary genomic approach, putative sHSP genes in the Solanum lycopersicum (cv. Heinz 1706) genome were investigated. A sHSP gene family of 33 members was established. Remarkably, roughly half of the members of this family can be explained by nine independent tandem duplication events that determined, evolutionarily, their functional fates. Within a mitochondrial class subfamily, only one duplicated member, Solyc08g078700, retained its ancestral chaperone function, while the others, Solyc08g078710 and Solyc08g078720, likely degenerated under neutrality and lack ancestral chaperone function. Functional conservation occurred within a cytosolic class I subfamily, whose four members, Solyc06g076570, Solyc06g076560, Solyc06g076540, and Solyc06g076520, support ∼57% of the total sHSP RNAm in the red ripe fruit. Subfunctionalization occurred within a new subfamily, whose two members, Solyc04g082720 and Solyc04g082740, show heterogeneous differential expression profiles during fruit ripening. These findings, involving the birth/death of some genes or the preferential/plastic expression of some others during fruit ripening, highlight the importance of tandem duplication events in the expansion of the sHSP gene family in the tomato genome. Despite its evolutionary diversity, the sHSP gene family in the tomato genome seems to be endowed with a core set of four homeostasis genes: Solyc05g014280, Solyc03g082420, Solyc11g020330, and Solyc06g076560, which appear to provide a baseline protection during both fruit ripening and heat shock stress in different tomato tissues. PMID:27565886

  8. Tandem Duplication Events in the Expansion of the Small Heat Shock Protein Gene Family in Solanum lycopersicum (cv. Heinz 1706

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    Flavia J. Krsticevic

    2016-10-01

    Full Text Available In plants, fruit maturation and oxidative stress can induce small heat shock protein (sHSP synthesis to maintain cellular homeostasis. Although the tomato reference genome was published in 2012, the actual number and functionality of sHSP genes remain unknown. Using a transcriptomic (RNA-seq and evolutionary genomic approach, putative sHSP genes in the Solanum lycopersicum (cv. Heinz 1706 genome were investigated. A sHSP gene family of 33 members was established. Remarkably, roughly half of the members of this family can be explained by nine independent tandem duplication events that determined, evolutionarily, their functional fates. Within a mitochondrial class subfamily, only one duplicated member, Solyc08g078700, retained its ancestral chaperone function, while the others, Solyc08g078710 and Solyc08g078720, likely degenerated under neutrality and lack ancestral chaperone function. Functional conservation occurred within a cytosolic class I subfamily, whose four members, Solyc06g076570, Solyc06g076560, Solyc06g076540, and Solyc06g076520, support ∼57% of the total sHSP RNAm in the red ripe fruit. Subfunctionalization occurred within a new subfamily, whose two members, Solyc04g082720 and Solyc04g082740, show heterogeneous differential expression profiles during fruit ripening. These findings, involving the birth/death of some genes or the preferential/plastic expression of some others during fruit ripening, highlight the importance of tandem duplication events in the expansion of the sHSP gene family in the tomato genome. Despite its evolutionary diversity, the sHSP gene family in the tomato genome seems to be endowed with a core set of four homeostasis genes: Solyc05g014280, Solyc03g082420, Solyc11g020330, and Solyc06g076560, which appear to provide a baseline protection during both fruit ripening and heat shock stress in different tomato tissues.

  9. An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals

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    Münk Carsten

    2012-05-01

    Full Text Available Abstract Background The APOBEC3 (A3 genes play a key role in innate antiviral defense in mammals by introducing directed mutations in the DNA. The human genome encodes for seven A3 genes, with multiple splice alternatives. Different A3 proteins display different substrate specificity, but the very basic question on how discerning self from non-self still remains unresolved. Further, the expression of A3 activity/ies shapes the way both viral and host genomes evolve. Results We present here a detailed temporal analysis of the origin and expansion of the A3 repertoire in mammals. Our data support an evolutionary scenario where the genome of the mammalian ancestor encoded for at least one ancestral A3 gene, and where the genome of the ancestor of placental mammals (and possibly of the ancestor of all mammals already encoded for an A3Z1-A3Z2-A3Z3 arrangement. Duplication events of the A3 genes have occurred independently in different lineages: humans, cats and horses. In all of them, gene duplication has resulted in changes in enzyme activity and/or substrate specificity, in a paradigmatic example of convergent adaptive evolution at the genomic level. Finally, our results show that evolutionary rates for the three A3Z1, A3Z2 and A3Z3 motifs have significantly decreased in the last 100 Mya. The analysis constitutes a textbook example of the evolution of a gene locus by duplication and sub/neofunctionalization in the context of virus-host arms race. Conclusions Our results provide a time framework for identifying ancestral and derived genomic arrangements in the APOBEC loci, and to date the expansion of this gene family for different lineages through time, as a response to changes in viral/retroviral/retrotransposon pressure.

  10. Rapid genome reshaping by multiple-gene loss after whole-genome duplication in teleost fish suggested by mathematical modeling.

    Science.gov (United States)

    Inoue, Jun; Sato, Yukuto; Sinclair, Robert; Tsukamoto, Katsumi; Nishida, Mutsumi

    2015-12-01

    Whole-genome duplication (WGD) is believed to be a significant source of major evolutionary innovation. Redundant genes resulting from WGD are thought to be lost or acquire new functions. However, the rates of gene loss and thus temporal process of genome reshaping after WGD remain unclear. The WGD shared by all teleost fish, one-half of all jawed vertebrates, was more recent than the two ancient WGDs that occurred before the origin of jawed vertebrates, and thus lends itself to analysis of gene loss and genome reshaping. Using a newly developed orthology identification pipeline, we inferred the post-teleost-specific WGD evolutionary histories of 6,892 protein-coding genes from nine phylogenetically representative teleost genomes on a time-calibrated tree. We found that rapid gene loss did occur in the first 60 My, with a loss of more than 70-80% of duplicated genes, and produced similar genomic gene arrangements within teleosts in that relatively short time. Mathematical modeling suggests that rapid gene loss occurred mainly by events involving simultaneous loss of multiple genes. We found that the subsequent 250 My were characterized by slow and steady loss of individual genes. Our pipeline also identified about 1,100 shared single-copy genes that are inferred to have become singletons before the divergence of clupeocephalan teleosts. Therefore, our comparative genome analysis suggests that rapid gene loss just after the WGD reshaped teleost genomes before the major divergence, and provides a useful set of marker genes for future phylogenetic analysis.

  11. Efficient inversions and duplications of mammalian regulatory DNA elements and gene clusters by CRISPR/Cas9

    Science.gov (United States)

    Li, Jinhuan; Shou, Jia; Guo, Ya; Tang, Yuanxiao; Wu, Yonghu; Jia, Zhilian; Zhai, Yanan; Chen, Zhifeng; Xu, Quan; Wu, Qiang

    2015-01-01

    The human genome contains millions of DNA regulatory elements and a large number of gene clusters, most of which have not been tested experimentally. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9) programed with a synthetic single-guide RNA (sgRNA) emerges as a method for genome editing in virtually any organisms. Here we report that targeted DNA fragment inversions and duplications could easily be achieved in human and mouse genomes by CRISPR with two sgRNAs. Specifically, we found that, in cultured human cells and mice, efficient precise inversions of DNA fragments ranging in size from a few tens of bp to hundreds of kb could be generated. In addition, DNA fragment duplications and deletions could also be generated by CRISPR through trans-allelic recombination between the Cas9-induced double-strand breaks (DSBs) on two homologous chromosomes (chromatids). Moreover, junctions of combinatorial inversions and duplications of the protocadherin (Pcdh) gene clusters induced by Cas9 with four sgRNAs could be detected. In mice, we obtained founders with alleles of precise inversions, duplications, and deletions of DNA fragments of variable sizes by CRISPR. Interestingly, we found that very efficient inversions were mediated by microhomology-mediated end joining (MMEJ) through short inverted repeats. We showed for the first time that DNA fragment inversions could be transmitted through germlines in mice. Finally, we applied this CRISPR method to a regulatory element of the Pcdhα cluster and found a new role in the regulation of members of the Pcdhγ cluster. This simple and efficient method should be useful in manipulating mammalian genomes to study millions of regulatory DNA elements as well as vast numbers of gene clusters. PMID:25757625

  12. Expression, subcellular localization, and cis-regulatory structure of duplicated phytoene synthase genes in melon (Cucumis melo L.).

    Science.gov (United States)

    Qin, Xiaoqiong; Coku, Ardian; Inoue, Kentaro; Tian, Li

    2011-10-01

    Carotenoids perform many critical functions in plants, animals, and humans. It is therefore important to understand carotenoid biosynthesis and its regulation in plants. Phytoene synthase (PSY) catalyzes the first committed and rate-limiting step in carotenoid biosynthesis. While PSY is present as a single copy gene in Arabidopsis, duplicated PSY genes have been identified in many economically important monocot and dicot crops. CmPSY1 was previously identified from melon (Cucumis melo L.), but was not functionally characterized. We isolated a second PSY gene, CmPSY2, from melon in this work. CmPSY2 possesses a unique intron/exon structure that has not been observed in other plant PSYs. Both CmPSY1 and CmPSY2 are functional in vitro, but exhibit distinct expression patterns in different melon tissues and during fruit development, suggesting differential regulation of the duplicated melon PSY genes. In vitro chloroplast import assays verified the plastidic localization of CmPSY1 and CmPSY2 despite the lack of an obvious plastid target peptide in CmPSY2. Promoter motif analysis of the duplicated melon and tomato PSY genes and the Arabidopsis PSY revealed distinctive cis-regulatory structures of melon PSYs and identified gibberellin-responsive motifs in all PSYs except for SlPSY1, which has not been reported previously. Overall, these data provide new insights into the evolutionary history of plant PSY genes and the regulation of PSY expression by developmental and environmental signals that may involve different regulatory networks.

  13. Gene fusions and gene duplications: relevance to genomic annotation and functional analysis

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    Riley Monica

    2005-03-01

    Full Text Available Abstract Background Escherichia coli a model organism provides information for annotation of other genomes. Our analysis of its genome has shown that proteins encoded by fused genes need special attention. Such composite (multimodular proteins consist of two or more components (modules encoding distinct functions. Multimodular proteins have been found to complicate both annotation and generation of sequence similar groups. Previous work overstated the number of multimodular proteins in E. coli. This work corrects the identification of modules by including sequence information from proteins in 50 sequenced microbial genomes. Results Multimodular E. coli K-12 proteins were identified from sequence similarities between their component modules and non-fused proteins in 50 genomes and from the literature. We found 109 multimodular proteins in E. coli containing either two or three modules. Most modules had standalone sequence relatives in other genomes. The separated modules together with all the single (un-fused proteins constitute the sum of all unimodular proteins of E. coli. Pairwise sequence relationships among all E. coli unimodular proteins generated 490 sequence similar, paralogous groups. Groups ranged in size from 92 to 2 members and had varying degrees of relatedness among their members. Some E. coli enzyme groups were compared to homologs in other bacterial genomes. Conclusion The deleterious effects of multimodular proteins on annotation and on the formation of groups of paralogs are emphasized. To improve annotation results, all multimodular proteins in an organism should be detected and when known each function should be connected with its location in the sequence of the protein. When transferring functions by sequence similarity, alignment locations must be noted, particularly when alignments cover only part of the sequences, in order to enable transfer of the correct function. Separating multimodular proteins into module units makes

  14. Duplication and Loss of Function of Genes Encoding RNA Polymerase III Subunit C4 Causes Hybrid Incompatibility in Rice

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    Giao Ngoc Nguyen

    2017-08-01

    Full Text Available Reproductive barriers are commonly observed in both animals and plants, in which they maintain species integrity and contribute to speciation. This report shows that a combination of loss-of-function alleles at two duplicated loci, DUPLICATED GAMETOPHYTIC STERILITY 1 (DGS1 on chromosome 4 and DGS2 on chromosome 7, causes pollen sterility in hybrid progeny derived from an interspecific cross between cultivated rice, Oryza sativa, and an Asian annual wild rice, O. nivara. Male gametes carrying the DGS1 allele from O. nivara (DGS1-nivaras and the DGS2 allele from O. sativa (DGS2-T65s were sterile, but female gametes carrying the same genotype were fertile. We isolated the causal gene, which encodes a protein homologous to DNA-dependent RNA polymerase (RNAP III subunit C4 (RPC4. RPC4 facilitates the transcription of 5S rRNAs and tRNAs. The loss-of-function alleles at DGS1-nivaras and DGS2-T65s were caused by weak or nonexpression of RPC4 and an absence of RPC4, respectively. Phylogenetic analysis demonstrated that gene duplication of RPC4 at DGS1 and DGS2 was a recent event that occurred after divergence of the ancestral population of Oryza from other Poaceae or during diversification of AA-genome species.

  15. Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome.

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    Emily Outwin

    2011-08-01

    Full Text Available A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR. Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression.

  16. Gene duplication and an accelerated evolutionary rate in 11S globulin genes are associated with higher protein synthesis in dicots as compared to monocots

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    Li Chun

    2012-01-01

    Full Text Available Abstract Background Seed storage proteins are a major source of dietary protein, and the content of such proteins determines both the quantity and quality of crop yield. Significantly, examination of the protein content in the seeds of crop plants shows a distinct difference between monocots and dicots. Thus, it is expected that there are different evolutionary patterns in the genes underlying protein synthesis in the seeds of these two groups of plants. Results Gene duplication, evolutionary rate and positive selection of a major gene family of seed storage proteins (the 11S globulin genes, were compared in dicots and monocots. The results, obtained from five species in each group, show more gene duplications, a higher evolutionary rate and positive selections of this gene family in dicots, which are rich in 11S globulins, but not in the monocots. Conclusion Our findings provide evidence to support the suggestion that gene duplication and an accelerated evolutionary rate may be associated with higher protein synthesis in dicots as compared to monocots.

  17. Heterogeneous expression pattern of tandem duplicated sHsps genes during fruit ripening in two tomato species

    Science.gov (United States)

    Arce, DP; Krsticevic, FJ; Ezpeleta, J.; Ponce, SD; Pratta, GR; Tapia, E.

    2016-04-01

    The small heat shock proteins (sHSPs) have been found to play a critical role in physiological stress conditions in protecting proteins from irreversible aggregation. To characterize the gene expression profile of four sHsps with a tandem gene structure arrangement in the domesticated Solanum lycopersicum (Heinz 1706) genome and its wild close relative Solanum pimpinellifolium (LA1589), differential gene expression analysis using RNA-Seq was conducted in three ripening stages in both cultivars fruits. Gene promoter analysis was performed to explain the heterogeneous pattern of gene expression found for these tandem duplicated sHsps. In silico analysis results contribute to refocus wet experiment analysis in tomato sHsp family proteins.

  18. Segmental duplication as one of the driving forces underlying the diversity of the human immunoglobulin heavy chain variable gene region

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    Gao Richeng

    2011-01-01

    Full Text Available Abstract Background Segmental duplication and deletion were implicated for a region containing the human immunoglobulin heavy chain variable (IGHV gene segments, 1.9III/hv3005 (possible allelic variants of IGHV3-30 and hv3019b9 (a possible allelic variant of IGHV3-33. However, very little is known about the ranges of the duplication and the polymorphic region. This is mainly because of the difficulty associated with distinguishing between allelic and paralogous sequences in the IGHV region containing extensive repetitive sequences. Inability to separate the two parental haploid genomes in the subjects is another serious barrier. To address these issues, unique DNA sequence tags evenly distributed within and flanking the duplicated region implicated by the previous studies were selected. The selected tags in single sperm from six unrelated healthy donors were amplified by multiplex PCR followed by microarray detection. In this way, individual haplotypes of different parental origins in the sperm donors could be analyzed separately and precisely. The identified polymorphic region was further analyzed at the nucleotide sequence level using sequences from the three human genomic sequence assemblies in the database. Results A large polymorphic region was identified using the selected sequence tags. Four of the 12 haplotypes were shown to contain consecutively undetectable tags spanning in a variable range. Detailed analysis of sequences from the genomic sequence assemblies revealed two large duplicate sequence blocks of 24,696 bp and 24,387 bp, respectively, and an incomplete copy of 961 bp in this region. It contains up to 13 IGHV gene segments depending on haplotypes. A polymorphic region was found to be located within the duplicated blocks. The variants of this polymorphism unusually diverged at the nucleotide sequence level and in IGHV gene segment number, composition and organization, indicating a limited selection pressure in general. However

  19. Duplication of the IGFBP-2 gene in teleost fish: protein structure and functionality conservation and gene expression divergence.

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    Jianfeng Zhou

    growth and development primarily by binding to and inhibiting IGF actions in vivo. The duplicated IGFBP-2 genes may provide additional flexibility in the regulation of IGF activities.

  20. Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor

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    Chan Jeannie

    2008-02-01

    Full Text Available Abstract Background Carboxylesterases (CES perform diverse metabolic roles in mammalian organisms in the detoxification of a broad range of drugs and xenobiotics and may also serve in specific roles in lipid, cholesterol, pheromone and lung surfactant metabolism. Five CES families have been reported in mammals with human CES1 and CES2 the most extensively studied. Here we describe the genetics, expression and phylogeny of CES isozymes in the opossum and report on the sequences and locations of CES1, CES2 and CES6 'like' genes within two gene clusters on chromosome one. We also discuss the likely sequence of gene duplication events generating multiple CES genes during vertebrate evolution. Results We report a cDNA sequence for an opossum CES and present evidence for CES1 and CES2 like genes expressed in opossum liver and intestine and for distinct gene locations of five opossum CES genes,CES1, CES2.1, CES2.2, CES2.3 and CES6, on chromosome 1. Phylogenetic and sequence alignment studies compared the predicted amino acid sequences for opossum CES with those for human, mouse, chicken, frog, salmon and Drosophila CES gene products. Phylogenetic analyses produced congruent phylogenetic trees depicting a rapid early diversification into at least five distinct CES gene family clusters: CES2, CES1, CES7, CES3, and CES6. Molecular divergence estimates based on a Bayesian relaxed clock approach revealed an origin for the five mammalian CES gene families between 328–378 MYA. Conclusion The deduced amino acid sequence for an opossum cDNA was consistent with its identity as a mammalian CES2 gene product (designated CES2.1. Distinct gene locations for opossum CES1 (1: 446,222,550–446,274,850, three CES2 genes (1: 677,773,395–677,927,030 and a CES6 gene (1: 677,585,520–677,730,419 were observed on chromosome 1. Opossum CES1 and multiple CES2 genes were expressed in liver and intestine. Amino acid sequences for opossum CES1 and three CES2 gene products

  1. ssb gene duplication restores the viability of ΔholC and ΔholD Escherichia coli mutants.

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    Stéphane Duigou

    2014-10-01

    Full Text Available The HolC-HolD (χψ complex is part of the DNA polymerase III holoenzyme (Pol III HE clamp-loader. Several lines of evidence indicate that both leading- and lagging-strand synthesis are affected in the absence of this complex. The Escherichia coli ΔholD mutant grows poorly and suppressor mutations that restore growth appear spontaneously. Here we show that duplication of the ssb gene, encoding the single-stranded DNA binding protein (SSB, restores ΔholD mutant growth at all temperatures on both minimal and rich medium. RecFOR-dependent SOS induction, previously shown to occur in the ΔholD mutant, is unaffected by ssb gene duplication, suggesting that lagging-strand synthesis remains perturbed. The C-terminal SSB disordered tail, which interacts with several E. coli repair, recombination and replication proteins, must be intact in both copies of the gene in order to restore normal growth. This suggests that SSB-mediated ΔholD suppression involves interaction with one or more partner proteins. ssb gene duplication also suppresses ΔholC single mutant and ΔholC ΔholD double mutant growth defects, indicating that it bypasses the need for the entire χψ complex. We propose that doubling the amount of SSB stabilizes HolCD-less Pol III HE DNA binding through interactions between SSB and a replisome component, possibly DnaE. Given that SSB binds DNA in vitro via different binding modes depending on experimental conditions, including SSB protein concentration and SSB interactions with partner proteins, our results support the idea that controlling the balance between SSB binding modes is critical for DNA Pol III HE stability in vivo, with important implications for DNA replication and genome stability.

  2. The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene

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    Volff Jean-Nicolas

    2010-12-01

    Full Text Available Abstract Background Members of the makorin (mkrn gene family encode RING/C3H zinc finger proteins with U3 ubiquitin ligase activity. Although these proteins have been described in a variety of eukaryotes such as plants, fungi, invertebrates and vertebrates including human, almost nothing is known about their structural and functional evolution. Results Via partial sequencing of a testis cDNA library from the poeciliid fish Xiphophorus maculatus, we have identified a new member of the makorin gene family, that we called mkrn4. In addition to the already described mkrn1 and mkrn2, mkrn4 is the third example of a makorin gene present in both tetrapods and ray-finned fish. However, this gene was not detected in mouse and rat, suggesting its loss in the lineage leading to rodent murids. Mkrn2 and mkrn4 are located in large ancient duplicated regions in tetrapod and fish genomes, suggesting the possible involvement of ancestral vertebrate-specific genome duplication in the formation of these genes. Intriguingly, many mkrn1 and mkrn2 intronless retrocopies have been detected in mammals but not in other vertebrates, most of them corresponding to pseudogenes. The nature and number of zinc fingers were found to be conserved in Mkrn1 and Mkrn2 but much more variable in Mkrn4, with lineage-specific differences. RT-qPCR analysis demonstrated a highly gonad-biased expression pattern for makorin genes in medaka and zebrafish (ray-finned fishes and amphibians, but a strong relaxation of this specificity in birds and mammals. All three mkrn genes were maternally expressed before zygotic genome activation in both medaka and zebrafish early embryos. Conclusion Our analysis demonstrates that the makorin gene family has evolved through large-scale duplication and subsequent lineage-specific retroposition-mediated duplications in vertebrates. From the three major vertebrate mkrn genes, mkrn4 shows the highest evolutionary dynamics, with lineage-specific loss of zinc

  3. Positive selection in the adhesion domain of Mus sperm Adam genes through gene duplications and function-driven gene complex formations.

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    Grayson, Phil; Civetta, Alberto

    2013-09-30

    Sperm and testes-expressed Adam genes have been shown to undergo bouts of positive selection in mammals. Despite the pervasiveness of positive selection signals, it is unclear what has driven such selective bouts. The fact that only sperm surface Adam genes show signals of positive selection within their adhesion domain has led to speculation that selection might be driven by species-specific adaptations to fertilization or sperm competition. Alternatively, duplications and neofunctionalization of Adam sperm surface genes, particularly as it is now understood in rodents, might have contributed to an acceleration of evolutionary rates and possibly adaptive diversification. Here we sequenced and conducted tests of selection within the adhesion domain of sixteen known sperm-surface Adam genes among five species of the Mus genus. We find evidence of positive selection associated with all six Adam genes known to interact to form functional complexes on Mus sperm. A subset of these complex-forming sperm genes also displayed accelerated branch evolution with Adam5 evolving under positive selection. In contrast to our previous findings in primates, selective bouts within Mus sperm Adams showed no associations to proxies of sperm competition. Expanded phylogenetic analysis including sequence data from other placental mammals allowed us to uncover ancient and recent episodes of adaptive evolution. The prevailing signals of rapid divergence and positive selection detected within the adhesion domain of interacting sperm Adams is driven by duplications and potential neofunctionalizations that are in some cases ancient (Adams 2, 3 and 5) or more recent (Adams 1b, 4b and 6).

  4. A new resource for characterizing X-linked genes in Drosophila melanogaster: systematic coverage and subdivision of the X chromosome with nested, Y-linked duplications.

    Science.gov (United States)

    Cook, R Kimberley; Deal, Megan E; Deal, Jennifer A; Garton, Russell D; Brown, C Adam; Ward, Megan E; Andrade, Rachel S; Spana, Eric P; Kaufman, Thomas C; Cook, Kevin R

    2010-12-01

    Interchromosomal duplications are especially important for the study of X-linked genes. Males inheriting a mutation in a vital X-linked gene cannot survive unless there is a wild-type copy of the gene duplicated elsewhere in the genome. Rescuing the lethality of an X-linked mutation with a duplication allows the mutation to be used experimentally in complementation tests and other genetic crosses and it maps the mutated gene to a defined chromosomal region. Duplications can also be used to screen for dosage-dependent enhancers and suppressors of mutant phenotypes as a way to identify genes involved in the same biological process. We describe an ongoing project in Drosophila melanogaster to generate comprehensive coverage and extensive breakpoint subdivision of the X chromosome with megabase-scale X segments borne on Y chromosomes. The in vivo method involves the creation of X inversions on attached-XY chromosomes by FLP-FRT site-specific recombination technology followed by irradiation to induce large internal X deletions. The resulting chromosomes consist of the X tip, a medial X segment placed near the tip by an inversion, and a full Y. A nested set of medial duplicated segments is derived from each inversion precursor. We have constructed a set of inversions on attached-XY chromosomes that enable us to isolate nested duplicated segments from all X regions. To date, our screens have provided a minimum of 78% X coverage with duplication breakpoints spaced a median of nine genes apart. These duplication chromosomes will be valuable resources for rescuing and mapping X-linked mutations and identifying dosage-dependent modifiers of mutant phenotypes.

  5. Enzymatic, expression and structural divergences among carboxyl O-methyltransferases after gene duplication and speciation in Nicotiana.

    Science.gov (United States)

    Hippauf, Frank; Michalsky, Elke; Huang, Ruiqi; Preissner, Robert; Barkman, Todd J; Piechulla, Birgit

    2010-02-01

    Methyl salicylate and methyl benzoate have important roles in a variety of processes including pollinator attraction and plant defence. These compounds are synthesized by salicylic acid, benzoic acid and benzoic acid/salicylic acid carboxyl methyltransferases (SAMT, BAMT and BSMT) which are members of the SABATH gene family. Both SAMT and BSMT were isolated from Nicotiana suaveolens, Nicotiana alata, and Nicotiana sylvestris allowing us to discern levels of enzyme divergence resulting from gene duplication in addition to species divergence. Phylogenetic analyses showed that Nicotiana SAMTs and BSMTs evolved in separate clades and the latter can be differentiated into the BSMT1 and the newly established BSMT2 branch. Although SAMT and BSMT orthologs showed minimal change coincident with species divergences, substantial evolutionary change of enzyme activity and expression patterns occurred following gene duplication. After duplication, the BSMT enzymes evolved higher preference for benzoic acid (BA) than salicylic acid (SA) whereas SAMTs maintained ancestral enzymatic preference for SA over BA. Expression patterns are largely complementary in that BSMT transcripts primarily accumulate in flowers, leaves and stems whereas SAMT is expressed mostly in roots. A novel enzyme, nicotinic acid carboxyl methyltransferase (NAMT), which displays a high degree of activity with nicotinic acid was discovered to have evolved in N. gossei from an ancestral BSMT. Furthermore a SAM-dependent synthesis of methyl anthranilate via BSMT2 is reported and contrasts with alternative biosynthetic routes previously proposed. While BSMT in flowers is clearly involved in methyl benzoate synthesis to attract pollinators, its function in other organs and tissues remains obscure.

  6. Diverged Copies of the Seed Regulatory Opaque-2 Gene by a Segmental Duplication in the Progenitor Genome of Rice,Sorghum,and Maize

    Institute of Scientific and Technical Information of China (English)

    Jian-Hong Xu; Joachim Messing

    2008-01-01

    Comparative analyses of the sequence of entire genomes have shown that gene duplications,chromosomal segmental duplications.or even whole genome duplications(WGD)have played prominent roles in the evolution of many eukaryotic species.Here,we used the ancient duplication of a well known transcription factor in maize,encoded by the Opaque-2(02)IOCUS,to examine the generaI features of divergences of chromosomaI segmentaI duplications in a lineagespecific manner.We took advantage of contiguous chromosomal sequence information in rice(Oryza sativa,Nipponbare).sorghum(Sorghum bicoloc Btx623),and maize(Zea mays,B73)that were aligned by conserved gene order(synteny).This analysis showed that the maize O2 locus is contained within a 1.25 million base-pair(Mb)segment on chromosome 7.which was duplicated≈56 million years ago(mya)before the split of rice and maize 50 mya.The duplicated region on chromosome 1 is only half the size and contains the maize OHP gene.which does not restore the o2 mutation although it encodes a protein with the same DNA and protein binding properties in endosperm.The segmental duplication iS not only found in rice,but also in sorghum,which split from maize 11.9 mya.A detailed analysis of the duplicated regions provided examples for complex rearrangements including deletions.duplications,conversions,inversions,and translocations.Furthermore,the rice and sorghum genomes appeared to be more stable than the maize genome,probably because maize underwent allotetraploidization and then diploidization.

  7. Similarity of DMD gene deletion and duplication in the Chinese patients compared to global populations

    Directory of Open Access Journals (Sweden)

    Yan Ming

    2008-04-01

    Full Text Available Abstract Background DNA deletion and duplication were determined as the major mutation underlying Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD. Method Applying multiplex ligation-dependent probe amplification (MLPA, we have analyzed 179 unrelated DMD/BMD subjects from northern China. Results Seventy-three percent of the subjects were found having a deletion (66.25% or duplication (6.25%. Exons 51–52 were detected as the most common fragment deleted in single-exon deletion, and the region of exons 45–50 was the most common exons deleted in multi-exon deletions. About 90% of DMD/BMD cases carry a small size deletion that involves 10 exons or less, 26.67% of which carry a single-exon deletion. Most of the smaller deletions resulted in an out-of-frame mutation. The most common exons deleted were determined to be between exon 48 and exon 52, with exon 50 was the model allele. Verifying single-exon deletion, one sample with a deletion of exon 53 that was initially observed from MLPA showed that there was a single base deletion that abolished the ligation site in MLPA. Confirmation of single-exon deletion is recommended to exclude single base deletion or mutation at the MLPA ligation site. Conclusion The frequency of deletion and duplication in northern China is similar to global ethnic populations.

  8. Becker Muscular Dystrophy (BMD) caused by duplication of exons 3-6 of the dystrophin gene presenting as dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsai, A.C.; Allingham-Hawkins, D.J.; Becker, L. [Univ. of Toronto, Ontario (Canada)] [and others

    1994-09-01

    X-linked dilated cardiomyopathy (XLCM) is a progressive myocardial disease presenting with congestive heart failure in teenage males without clinical signs of skeletal myopathy. Tight linkage of XLCM to the DMD locus has been demonstrated; it has been suggested that, at least in some families, XLCM is a {open_quotes}dystrophinopathy.{close_quotes} We report a 14-year-old boy who presented with acute heart failure due to dilated cardiomyopathy. He had no history of muscle weakness, but physical examination revealed pseudohypertrophy of the calf muscles. He subsequently received a heart transplantation. Family history was negative. Serum CK level at the time of diagnosis was 10,416. Myocardial biopsy showed no evidence of carditis. Dystrophin staining of cardiac and skeletal muscle with anti-sera to COOH and NH{sub 2}termini showed a patchy distribution of positivity suggestive of Becker muscular dystrophy. Analysis of 18 of the 79 dystrophin exons detected a duplication that included exons 3-6. The proband`s mother has an elevated serum CK and was confirmed to be a carrier of the same duplication. A mutation in the muscle promotor region of the dystrophin gene has been implicated in the etiology of SLCM. However, Towbin et al. (1991) argued that other 5{prime} mutations in the dystrophin gene could cause selective cardiomyopathy. The findings in our patient support the latter hypothesis. This suggests that there are multiple regions in the dystrophin gene which, when disrupted, can cause isolated dilated cardiomyopathy.

  9. Original tandem duplication in FXIIIA gene with splicing site modification and four amino acids insertion causes factor XIII deficiency.

    Science.gov (United States)

    Louhichi, Nacim; Haj Salem, Ikhlass; Medhaffar, Moez; Miled, Nabil; Hadji, Ahmad F; Keskes, Leila; Fakhfakh, Faiza

    2017-04-01

    : Recessive mutations of F13A gene are reported to be responsible of FXIIIA subunit deficiency (FXIIIA). In all, some intronic nucleotide changes identified in this gene were investigated by in-silico analysis and occasionally supported by experimental data or reported in some cases as a polymorphism. To determine the molecular defects responsible of congenital factor XIII deficiency in Libyan patient, molecular analysis was performed by direct DNA sequencing of the coding regions and splice junctions of the FXIIIA subunit gene (F13A). A splicing minigene assay was used to study the effect of this mutation. Bioinformatics exploration was fulfilled to conceive consequences on protein. A 12-bp duplication straddling the border of intron 9 and exon 10 leads to two 3' acceptor splice sites, resulting in silencing of the downstream wild 3' splice site. It caused an in-frame insertion of 12 nucleotides into mRNA and four amino acids into protein. Bioinformatic analysis predicts that the insertion of four amino acids affects the site 3 of calcium binding site, which disturbs the smooth function of the FXIIIA peptide causing the factor XIII deficiency. This study showed that a small duplication seems to weaken the original 3' splice site and enhance the activation of a new splice site responsible for an alternative splicing. It would be interesting to examine the underlying molecular mechanism involved in this rearrangement.

  10. Antagonistic roles for KNOX1 and KNOX2 genes in patterning the land plant body plan following an ancient gene duplication.

    Science.gov (United States)

    Furumizu, Chihiro; Alvarez, John Paul; Sakakibara, Keiko; Bowman, John L

    2015-02-01

    Neofunctionalization following gene duplication is thought to be one of the key drivers in generating evolutionary novelty. A gene duplication in a common ancestor of land plants produced two classes of KNOTTED-like TALE homeobox genes, class I (KNOX1) and class II (KNOX2). KNOX1 genes are linked to tissue proliferation and maintenance of meristematic potentials of flowering plant and moss sporophytes, and modulation of KNOX1 activity is implicated in contributing to leaf shape diversity of flowering plants. While KNOX2 function has been shown to repress the gametophytic (haploid) developmental program during moss sporophyte (diploid) development, little is known about KNOX2 function in flowering plants, hindering syntheses regarding the relationship between two classes of KNOX genes in the context of land plant evolution. Arabidopsis plants harboring loss-of-function KNOX2 alleles exhibit impaired differentiation of all aerial organs and have highly complex leaves, phenocopying gain-of-function KNOX1 alleles. Conversely, gain-of-function KNOX2 alleles in conjunction with a presumptive heterodimeric BELL TALE homeobox partner suppressed SAM activity in Arabidopsis and reduced leaf complexity in the Arabidopsis relative Cardamine hirsuta, reminiscent of loss-of-function KNOX1 alleles. Little evidence was found indicative of epistasis or mutual repression between KNOX1 and KNOX2 genes. KNOX proteins heterodimerize with BELL TALE homeobox proteins to form functional complexes, and contrary to earlier reports based on in vitro and heterologous expression, we find high selectivity between KNOX and BELL partners in vivo. Thus, KNOX2 genes confer opposing activities rather than redundant roles with KNOX1 genes, and together they act to direct the development of all above-ground organs of the Arabidopsis sporophyte. We infer that following the KNOX1/KNOX2 gene duplication in an ancestor of land plants, neofunctionalization led to evolution of antagonistic biochemical

  11. Whole-gene positive selection, elevated synonymous substitution rates, duplication, and indel evolution of the chloroplast clpP1 gene.

    Directory of Open Access Journals (Sweden)

    Per Erixon

    Full Text Available BACKGROUND: Synonymous DNA substitution rates in the plant chloroplast genome are generally relatively slow and lineage dependent. Non-synonymous rates are usually even slower due to purifying selection acting on the genes. Positive selection is expected to speed up non-synonymous substitution rates, whereas synonymous rates are expected to be unaffected. Until recently, positive selection has seldom been observed in chloroplast genes, and large-scale structural rearrangements leading to gene duplications are hitherto supposed to be rare. METHODOLOGY/PRINCIPLE FINDINGS: We found high substitution rates in the exons of the plastid clpP1 gene in Oenothera (the Evening Primrose family and three separate lineages in the tribe Sileneae (Caryophyllaceae, the Carnation family. Introns have been lost in some of the lineages, but where present, the intron sequences have substitution rates similar to those found in other introns of their genomes. The elevated substitution rates of clpP1 are associated with statistically significant whole-gene positive selection in three branches of the phylogeny. In two of the lineages we found multiple copies of the gene. Neighboring genes present in the duplicated fragments do not show signs of elevated substitution rates or positive selection. Although non-synonymous substitutions account for most of the increase in substitution rates, synonymous rates are also markedly elevated in some lineages. Whereas plant clpP1 genes experiencing negative (purifying selection are characterized by having very conserved lengths, genes under positive selection often have large insertions of more or less repetitive amino acid sequence motifs. CONCLUSIONS/SIGNIFICANCE: We found positive selection of the clpP1 gene in various plant lineages to correlated with repeated duplication of the clpP1 gene and surrounding regions, repetitive amino acid sequences, and increase in synonymous substitution rates. The present study sheds light on the

  12. Selection shaped the evolution of mouse androgen-binding protein (ABP) function and promoted the duplication of Abp genes.

    Science.gov (United States)

    Karn, Robert C; Laukaitis, Christina M

    2014-08-01

    In the present article, we summarize two aspects of our work on mouse ABP (androgen-binding protein): (i) the sexual selection function producing incipient reinforcement on the European house mouse hybrid zone, and (ii) the mechanism behind the dramatic expansion of the Abp gene region in the mouse genome. Selection unifies these two components, although the ways in which selection has acted differ. At the functional level, strong positive selection has acted on key sites on the surface of one face of the ABP dimer, possibly to influence binding to a receptor. A different kind of selection has apparently driven the recent and rapid expansion of the gene region, probably by increasing the amount of Abp transcript, in one or both of two ways. We have shown previously that groups of Abp genes behave as LCRs (low-copy repeats), duplicating as relatively large blocks of genes by NAHR (non-allelic homologous recombination). The second type of selection involves the close link between the accumulation of L1 elements and the expansion of the Abp gene family by NAHR. It is probably predicated on an initial selection for increased transcription of existing Abp genes and/or an increase in Abp gene number providing more transcriptional sites. Either or both could increase initial transcript production, a quantitative change similar to increasing the volume of a radio transmission. In closing, we also provide a note on Abp gene nomenclature.

  13. Gene Duplication of the zebrafish kit ligand and partitioning of melanocyte development functions to kit ligand a.

    Directory of Open Access Journals (Sweden)

    Keith A Hultman

    2007-01-01

    Full Text Available The retention of particular genes after the whole genome duplication in zebrafish has given insights into how genes may evolve through partitioning of ancestral functions. We examine the partitioning of expression patterns and functions of two zebrafish kit ligands, kit ligand a (kitla and kit ligand b (kitlb, and discuss their possible coevolution with the duplicated zebrafish kit receptors (kita and kitb. In situ hybridizations show that kitla mRNA is expressed in the trunk adjacent to the notochord in the middle of each somite during stages of melanocyte migration and later expressed in the skin, when the receptor is required for melanocyte survival. kitla is also expressed in other regions complementary to kita receptor expression, including the pineal gland, tail bud, and ear. In contrast, kitlb mRNA is expressed in brain ventricles, ear, and cardinal vein plexus, in regions generally not complementary to either zebrafish kit receptor ortholog. However, like kitla, kitlb is expressed in the skin during stages consistent with melanocyte survival. Thus, it appears that kita and kitla have maintained congruent expression patterns, while kitb and kitlb have evolved divergent expression patterns. We demonstrate the interaction of kita and kitla by morpholino knockdown analysis. kitla morphants, but not kitlb morphants, phenocopy the null allele of kita, with defects for both melanocyte migration and survival. Furthermore, kitla morpholino, but not kitlb morpholino, interacts genetically with a sensitized allele of kita, confirming that kitla is the functional ligand to kita. Last, we examine kitla overexpression in embryos, which results in hyperpigmentation caused by an increase in the number and size of melanocytes. This hyperpigmentation is dependent on kita function. We conclude that following genome duplication, kita and kitla have maintained their receptor-ligand relationship, coevolved complementary expression patterns, and that

  14. Collateral damage: Spread of repeat-induced point mutation from a duplicated DNA sequence into an adjoining single-copy gene in Neurospora crassa

    Indian Academy of Sciences (India)

    Meenal Vyas; Durgadas P Kasbekar

    2005-02-01

    Repeat-induced point mutation (RIP) is an unusual genome defense mechanism that was discovered in Neurospora crassa. RIP occurs during a sexual cross and induces numerous G : C to A : T mutations in duplicated DNA sequences and also methylates many of the remaining cytosine residues. We measured the susceptibility of the erg-3 gene, present in single copy, to the spread of RIP from duplications of adjoining sequences. Genomic segments of defined length (1, 1.5 or 2 kb) and located at defined distances (0, 0.5, 1 or 2 kb) upstream or downstream of the erg-3 open reading frame (ORF) were amplified by polymerase chain reaction (PCR), and the duplications were created by transformation of the amplified DNA. Crosses were made with the duplication strains and the frequency of erg-3 mutant progeny provided a measure of the spread of RIP from the duplicated segments into the erg-3 gene. Our results suggest that ordinarily RIP-spread does not occur. However, occasionally the mechanism that confines RIP to the duplicated segment seems to fail (frequency 0.1–0.8%) and then RIP can spread across as much as 1 kb of unduplicated DNA. Additionally, the bacterial hph gene appeared to be very susceptible to the spread of RIP-associated cytosine methylation.

  15. Balanced gene losses, duplications and intensive rearrangements led to an unusual regularly sized genome in Arbutus unedo chloroplasts.

    Directory of Open Access Journals (Sweden)

    Fernando Martínez-Alberola

    Full Text Available Completely sequenced plastomes provide a valuable source of information about the duplication, loss, and transfer events of chloroplast genes and phylogenetic data for resolving relationships among major groups of plants. Moreover, they can also be useful for exploiting chloroplast genetic engineering technology. Ericales account for approximately six per cent of eudicot diversity with 11,545 species from which only three complete plastome sequences are currently available. With the aim of increasing the number of ericalean complete plastome sequences, and to open new perspectives in understanding Mediterranean plant adaptations, a genomic study on the basis of the complete chloroplast genome sequencing of Arbutus unedo and an updated phylogenomic analysis of Asteridae was implemented. The chloroplast genome of A. unedo shows extensive rearrangements but a medium size (150,897 nt in comparison to most of angiosperms. A number of remarkable distinct features characterize the plastome of A. unedo: five-fold dismissing of the SSC region in relation to most angiosperms; complete loss or pseudogenization of a number of essential genes; duplication of the ndhH-D operon and its location within the two IRs; presence of large tandem repeats located near highly re-arranged regions and pseudogenes. All these features outline the primary evolutionary split between Ericaceae and other ericalean families. The newly sequenced plastome of A. unedo with the available asterid sequences allowed the resolution of some uncertainties in previous phylogenies of Asteridae.

  16. Multiplex ligation-dependent probe amplification for rapid detection of deletions and duplications in the dystrophin gene

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked disorders caused by mutations in the dystrophin gene. The majority of recognized mutations are copy number changes of individual exons. The objective of the present study was to assess the multiplex ligation-dependent probe amplification (MLPA) effects of detection of gene mutations. Methods: Samples of 20 control males and 80 males and their mothers referred to our diagnostic facility on the clinical suspicion of DMD or BMD were tested by MLPA and multiplex PCR. Results: The mean DQs for all peak of 20 control male samples was 1.02 (range from 0.83 to 1.21) by MLPA. Deletions or duplications were identified in 6 out of 31 families that had been previously tested as negative by multiplex PCR. One case of complex rearrangement involving a duplication of two regions: dupEX3-9 and dupEX 17-41 were found by MLPA. Conclusions: MLPA is a highly sensitive method and rapid alternative to multiplex PCR for detection of DMD and BMD.

  17. Interlocus gene conversion explains at least 2.7% of single nucleotide variants in human segmental duplications.

    Science.gov (United States)

    Dumont, Beth L

    2015-06-16

    Interlocus gene conversion (IGC) is a recombination-based mechanism that results in the unidirectional transfer of short stretches of sequence between paralogous loci. Although IGC is a well-established mechanism of human disease, the extent to which this mutagenic process has shaped overall patterns of segregating variation in multi-copy regions of the human genome remains unknown. One expected manifestation of IGC in population genomic data is the presence of one-to-one paralogous SNPs that segregate identical alleles. Here, I use SNP genotype calls from the low-coverage phase 3 release of the 1000 Genomes Project to identify 15,790 parallel, shared SNPs in duplicated regions of the human genome. My approach for identifying these sites accounts for the potential redundancy of short read mapping in multi-copy genomic regions, thereby effectively eliminating false positive SNP calls arising from paralogous sequence variation. I demonstrate that independent mutation events to identical nucleotides at paralogous sites are not a significant source of shared polymorphisms in the human genome, consistent with the interpretation that these sites are the outcome of historical IGC events. These putative signals of IGC are enriched in genomic contexts previously associated with non-allelic homologous recombination, including clear signals in gene families that form tandem intra-chromosomal clusters. Taken together, my analyses implicate IGC, not point mutation, as the mechanism generating at least 2.7% of single nucleotide variants in duplicated regions of the human genome.

  18. Duplications and positive selection drive the evolution of parasitism associated gene families in the nematode Strongyloides papillosus.

    Science.gov (United States)

    Baskaran, Praveen; Jaleta, Tegegn G; Streit, Adrian; Rödelsperger, Christian

    2017-03-02

    Gene duplication is one major mechanism playing a role in the evolution of phenotypic complexity and in the generation of novel traits. By comparing parasitic and nonparasitic nematodes, a recent study found that the evolution of parasitism in Strongyloididae is associated with a large expansion in the Astacin and CAP gene families.To gain novel insights into the developmental processes in the sheep parasite Strongyloides papillosus, we sequenced transcriptomes of different developmental stages and sexes. Overall, we found that the majority of genes are developmentally regulated and have one-to-one orthologs in the diverged S. ratti genome. Together with the finding of similar expression profiles between S. papillosus and S. ratti, these results indicate a strong evolutionary constraint acting against change at sequence and expression levels. However, the comparison between parasitic and free-living females demonstrates a quite divergent pattern that is mostly due to the previously mentioned expansion in the Astacin and CAP gene families. More detailed phylogenetic analysis of both gene families shows that most members date back to single expansion events early in the Strongyloides lineage and have undergone subfunctionalization resulting in clusters that are highly expressed either in infective larvae or in parasitic females. Finally, we found increased evidence for positive selection in both gene families relative to the genome-wide expectation.In summary, our study reveals first insights into the developmental transcriptomes of S. papillosus and provides a detailed analysis of sequence and expression evolution in parasitism associated gene families.

  19. Deletion/duplication mutation screening of TP53 gene in patients with transitional cell carcinoma of urinary bladder using multiplex ligation-dependent probe amplification.

    Science.gov (United States)

    Bazrafshani, Mohammad Reza R; Nowshadi, Pouriaali A; Shirian, Sadegh; Daneshbod, Yahya; Nabipour, Fatemeh; Mokhtari, Maral; Hosseini, Fatemehsadat; Dehghan, Somayeh; Saeedzadeh, Abolfazl; Mosayebi, Ziba

    2016-02-01

    Bladder cancer is a molecular disease driven by the accumulation of genetic, epigenetic, and environmental factors. The aim of this study was to detect the deletions/duplication mutations in TP53 gene exons using multiplex ligation-dependent probe amplification (MLPA) method in the patients with transitional cell carcinoma (TCC). The achieved formalin-fixed paraffin-embedded tissues from 60 patients with TCC of bladder were screened for exonal deletions or duplications of every 12 TP53 gene exons using MLPA. The pathological sections were examined by three pathologists and categorized according to the WHO scoring guideline as 18 (30%) grade I, 22 (37%) grade II, 13 (22%) grade III, and 7 (11%) grade IV cases of TCC. None mutation changes of TP53 gene were detected in 24 (40%) of the patients. Furthermore, mutation changes including, 15 (25%) deletion, 17 (28%) duplication, and 4 (7%) both deletion and duplication cases were observed among 60 samples. From 12 exons of TP53 gene, exon 1 was more subjected to exonal deletion. Deletion of exon 1 of TP53 gene has occurred in 11 (35.4%) patients with TCC. In general, most mutations of TP53, either deletion or duplication, were found in exon 1, which was statistically significant. In addition, no relation between the TCC tumor grade and any type of mutation were observed in this research. MLPA is a simple and efficient method to analyze genomic deletions and duplications of all 12 exons of TP53 gene. The finding of this report that most of the mutations of TP53 occur in exon 1 is in contrast to that of the other reports suggesting that exons 5-8 are the most (frequently) mutated exons of TP53 gene. The mutations of exon 1 of TP53 gene may play an important role in the tumorogenesis of TCC.

  20. Evidence of neofunctionalization after the duplication of the highly conserved Polycomb group gene Caf1-55 in the obscura group of Drosophila.

    Science.gov (United States)

    Calvo-Martín, Juan M; Papaceit, Montserrat; Segarra, Carmen

    2017-01-17

    Drosophila CAF1-55 protein is a subunit of the Polycomb repressive complex PRC2 and other protein complexes. It is a multifunctional and evolutionarily conserved protein that participates in nucleosome assembly and remodelling, as well as in the epigenetic regulation of a large set of target genes. Here, we describe and analyze the duplication of Caf1-55 in the obscura group of Drosophila. Paralogs exhibited a strong asymmetry in evolutionary rates, which suggests that they have evolved according to a neofunctionalization process. During this process, the ancestral copy has been kept under steady purifying selection to retain the ancestral function and the derived copy (Caf1-55dup) that originated via a DNA-mediated duplication event ~18 Mya, has been under clear episodic selection. Different maximum likelihood approaches confirmed the action of positive selection, in contrast to relaxed selection, on Caf1-55dup after the duplication. This adaptive process has also taken place more recently during the divergence of D. subobscura and D. guanche. The possible association of this duplication with a previously detected acceleration in the evolutionary rate of three CAF1-55 partners in PRC2 complexes is discussed. Finally, the timing and functional consequences of the Caf1-55 duplication is compared to other duplications of Polycomb genes.

  1. The nuclear OXPHOS genes in insecta: a common evolutionary origin, a common cis-regulatory motif, a common destiny for gene duplicates

    Directory of Open Access Journals (Sweden)

    Pesole Graziano

    2007-11-01

    Full Text Available Abstract Background When orthologous sequences from species distributed throughout an optimal range of divergence times are available, comparative genomics is a powerful tool to address problems such as the identification of the forces that shape gene structure during evolution, although the functional constraints involved may vary in different genes and lineages. Results We identified and annotated in the MitoComp2 dataset the orthologs of 68 nuclear genes controlling oxidative phosphorylation in 11 Drosophilidae species and in five non-Drosophilidae insects, and compared them with each other and with their counterparts in three vertebrates (Fugu rubripes, Danio rerio and Homo sapiens and in the cnidarian Nematostella vectensis, taking into account conservation of gene structure and regulatory motifs, and preservation of gene paralogs in the genome. Comparative analysis indicates that the ancestral insect OXPHOS genes were intron rich and that extensive intron loss and lineage-specific intron gain occurred during evolution. Comparison with vertebrates and cnidarians also shows that many OXPHOS gene introns predate the cnidarian/Bilateria evolutionary split. The nuclear respiratory gene element (NRG has played a key role in the evolution of the insect OXPHOS genes; it is constantly conserved in the OXPHOS orthologs of all the insect species examined, while their duplicates either completely lack the element or possess only relics of the motif. Conclusion Our observations reinforce the notion that the common ancestor of most animal phyla had intron-rich gene, and suggest that changes in the pattern of expression of the gene facilitate the fixation of duplications in the genome and the development of novel genetic functions.

  2. Duplication at Xq13.3-q21.1 with syndromic intellectual disability, a probable role for the ATRX gene.

    Science.gov (United States)

    Martínez, Francisco; Roselló, Mónica; Mayo, Sonia; Monfort, Sandra; Oltra, Silvestre; Orellana, Carmen

    2014-04-01

    Here we report on two unrelated male patients with syndromic intellectual disability (ID) due to duplication at Xq13.3-q21.1, a region of about 6 Mb and 25 genes. Among these, the most outstanding is ATRX, the causative gene of X-linked alpha-thalassemia/mental retardation. ATRX belongs to the growing list of genes implied in chromatin remodeling causing ID. Many these genes, such as MECP2, are dose-sensitive so that not only deletions and point mutations, but also duplications cause ID. Both patients have severe ID, absent expressive speech, early hypotonia, behavior problems (hyperactivity, repetitive self-stimulatory behavior), postnatal growth deficiency, microcephaly, micrognathia, cryptorchidism, low-set, posteriorly angulated ears, and downslanting palpebral fissures. These findings are also usually present among patients with loss-of-function mutations of the ATRX gene. Completely skewed X inactivation was observed in the only informative carrier mother, a constant finding among female carriers of inactivating point mutations of this gene. Participation of other duplicated genes cannot be excluded; nevertheless we propose that the increased dosage of ATRX is the major pathogenic mechanism of this X-linked disorder, a syndrome reminiscent of MECP2 duplication.

  3. Ancient Duplications and Expression Divergence in the Globin Gene Superfamily of Vertebrates: Insights from the Elephant Shark Genome and Transcriptome.

    Science.gov (United States)

    Opazo, Juan C; Lee, Alison P; Hoffmann, Federico G; Toloza-Villalobos, Jessica; Burmester, Thorsten; Venkatesh, Byrappa; Storz, Jay F

    2015-07-01

    Comparative analyses of vertebrate genomes continue to uncover a surprising diversity of genes in the globin gene superfamily, some of which have very restricted phyletic distributions despite their antiquity. Genomic analysis of the globin gene repertoire of cartilaginous fish (Chondrichthyes) should be especially informative about the duplicative origins and ancestral functions of vertebrate globins, as divergence between Chondrichthyes and bony vertebrates represents the most basal split within the jawed vertebrates. Here, we report a comparative genomic analysis of the vertebrate globin gene family that includes the complete globin gene repertoire of the elephant shark (Callorhinchus milii). Using genomic sequence data from representatives of all major vertebrate classes, integrated analyses of conserved synteny and phylogenetic relationships revealed that the last common ancestor of vertebrates possessed a repertoire of at least seven globin genes: single copies of androglobin and neuroglobin, four paralogous copies of globin X, and the single-copy progenitor of the entire set of vertebrate-specific globins. Combined with expression data, the genomic inventory of elephant shark globins yielded four especially surprising findings: 1) there is no trace of the neuroglobin gene (a highly conserved gene that is present in all other jawed vertebrates that have been examined to date), 2) myoglobin is highly expressed in heart, but not in skeletal muscle (reflecting a possible ancestral condition in vertebrates with single-circuit circulatory systems), 3) elephant shark possesses two highly divergent globin X paralogs, one of which is preferentially expressed in gonads, and 4) elephant shark possesses two structurally distinct α-globin paralogs, one of which is preferentially expressed in the brain. Expression profiles of elephant shark globin genes reveal distinct specializations of function relative to orthologs in bony vertebrates and suggest hypotheses about

  4. Translocations used to generate chromosome segment duplications in Neurospora can disrupt genes and create novel open reading frames

    Indian Academy of Sciences (India)

    Parmit K Singh; Srividhya V Iyer; T Naga Sowjanya; B Kranthi Raj; Durgadas P Kasbekar

    2010-12-01

    In Neurospora crassa, crosses between normal sequence strains and strains bearing some translocations can yield progeny bearing a duplication (Dp) of the translocated chromosome segment. Here, 30 breakpoint junction sequences of 12 Dp-generating translocations were determined. The breakpoints disrupted 13 genes (including predicted genes), and created 10 novel open reading frames. Insertion of sequences from LG III into LG I as translocation T(UK818) disrupts the eat-3 gene, which is the ortholog of the Podospora anserine gene ami1. Since ami1-homozygous Podospora crosses were reported to increase the frequency of repeat-induced point mutation (RIP), we performed crosses homozygous for a deficiency in eat-3 to test for a corresponding increase in RIP frequency. However, our results suggested that, unlike in Podospora, the eat-3 gene might be essential for ascus development in Neurospora. Duplication–heterozygous crosses are generally barren in Neurospora; however, by using molecular probes developed in this study, we could identify Dp segregants from two different translocation–heterozygous crosses, and using these we found that the barren phenotype of at least some duplication–heterozygous crosses was incompletely penetrant.

  5. Autopolyploidy genome duplication preserves other ancient genome duplications in Atlantic salmon (Salmo salar)

    Science.gov (United States)

    Davidson, William S.

    2017-01-01

    Salmonids (e.g. Atlantic salmon, Pacific salmon, and trouts) have a long legacy of genome duplication. In addition to three ancient genome duplications that all teleosts are thought to share, salmonids have had one additional genome duplication. We explored a methodology for untangling these duplications from each other to better understand them in Atlantic salmon. In this methodology, homeologous regions (paralogous/duplicated genomic regions originating from a whole genome duplication) from the most recent genome duplication were assumed to have duplicated genes at greater density and have greater sequence similarity. This assumption was used to differentiate duplicated gene pairs in Atlantic salmon that are either from the most recent genome duplication or from earlier duplications. From a comparison with multiple vertebrate species, it is clear that Atlantic salmon have retained more duplicated genes from ancient genome duplications than other vertebrates--often at higher density in the genome and containing fewer synonymous mutations. It may be that polysomic inheritance is the mechanism responsible for maintaining ancient gene duplicates in salmonids. Polysomic inheritance (when multiple chromosomes pair during meiosis) is thought to be relatively common in salmonids compared to other vertebrate species. These findings illuminate how genome duplications may not only increase the number of duplicated genes, but may also be involved in the maintenance of them from previous genome duplications as well. PMID:28241055

  6. Different expression patterns of duplicated PHANTASTICA-like genes in Lotus japonicus suggest their divergent functions during compound leaf development

    Institute of Scientific and Technical Information of China (English)

    Jiang Hong LUO; Jun YAN; Lin WENG; Jun YANG; Zhong ZHAO; Jiang Hua CHEN; Xiao He HU; Da LUO

    2005-01-01

    Recent studies on leaf development demonstrate that the mechanism on the adaxial-abaxial polarity pattern formation could be well conserved among the far-related species, in which PHANTASTICA (PAHN)-like genes play important roles. In this study, we explored the conservation and diversity on functions of PHAN-like genes during the compound leaf development in Lotusjaponicus, a papilionoid legume. Two PHAN-like genes in L. japonicus, LjPHANa and LjPHANb,were found to originate from a gene duplication event and displayed different expression patterns during compound leaf development. Two mutants, reduced leaflets1 (rel1) and reduced leaflets3 (rel3), which exhibited decreased adaxial identity of leaflets and reduced leaflet initiation, were identified and investigated. The expression patterns of both LjPHANs in rel mutants were altered and correlated with abnormalities of compound leaves. Our data suggest that LjPHANa and LjPHANb play important but divergent roles in regulating adaxial-abaxial polarity of compound leaves in L. japonicus.

  7. Antagonistic roles for KNOX1 and KNOX2 genes in patterning the land plant body plan following an ancient gene duplication.

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    Chihiro Furumizu

    2015-02-01

    Full Text Available Neofunctionalization following gene duplication is thought to be one of the key drivers in generating evolutionary novelty. A gene duplication in a common ancestor of land plants produced two classes of KNOTTED-like TALE homeobox genes, class I (KNOX1 and class II (KNOX2. KNOX1 genes are linked to tissue proliferation and maintenance of meristematic potentials of flowering plant and moss sporophytes, and modulation of KNOX1 activity is implicated in contributing to leaf shape diversity of flowering plants. While KNOX2 function has been shown to repress the gametophytic (haploid developmental program during moss sporophyte (diploid development, little is known about KNOX2 function in flowering plants, hindering syntheses regarding the relationship between two classes of KNOX genes in the context of land plant evolution. Arabidopsis plants harboring loss-of-function KNOX2 alleles exhibit impaired differentiation of all aerial organs and have highly complex leaves, phenocopying gain-of-function KNOX1 alleles. Conversely, gain-of-function KNOX2 alleles in conjunction with a presumptive heterodimeric BELL TALE homeobox partner suppressed SAM activity in Arabidopsis and reduced leaf complexity in the Arabidopsis relative Cardamine hirsuta, reminiscent of loss-of-function KNOX1 alleles. Little evidence was found indicative of epistasis or mutual repression between KNOX1 and KNOX2 genes. KNOX proteins heterodimerize with BELL TALE homeobox proteins to form functional complexes, and contrary to earlier reports based on in vitro and heterologous expression, we find high selectivity between KNOX and BELL partners in vivo. Thus, KNOX2 genes confer opposing activities rather than redundant roles with KNOX1 genes, and together they act to direct the development of all above-ground organs of the Arabidopsis sporophyte. We infer that following the KNOX1/KNOX2 gene duplication in an ancestor of land plants, neofunctionalization led to evolution of antagonistic

  8. New organelles by gene duplication in a biophysical model of eukaryote endomembrane evolution

    National Research Council Canada - National Science Library

    Ramadas, Rohini; Thattai, Mukund

    2013-01-01

    .... This endomembrane system arose and diversified during a period characterized by massive expansions of gene families involved in trafficking after the acquisition of a mitochondrial endosymbiont...

  9. Independent and Parallel Evolution of New Genes by Gene Duplication in Two Origins of C4 Photosynthesis Provides New Insight into the Mechanism of Phloem Loading in C4 Species.

    Science.gov (United States)

    Emms, David M; Covshoff, Sarah; Hibberd, Julian M; Kelly, Steven

    2016-07-01

    C4 photosynthesis is considered one of the most remarkable examples of evolutionary convergence in eukaryotes. However, it is unknown whether the evolution of C4 photosynthesis required the evolution of new genes. Genome-wide gene-tree species-tree reconciliation of seven monocot species that span two origins of C4 photosynthesis revealed that there was significant parallelism in the duplication and retention of genes coincident with the evolution of C4 photosynthesis in these lineages. Specifically, 21 orthologous genes were duplicated and retained independently in parallel at both C4 origins. Analysis of this gene cohort revealed that the set of parallel duplicated and retained genes is enriched for genes that are preferentially expressed in bundle sheath cells, the cell type in which photosynthesis was activated during C4 evolution. Furthermore, functional analysis of the cohort of parallel duplicated genes identified SWEET-13 as a potential key transporter in the evolution of C4 photosynthesis in grasses, and provides new insight into the mechanism of phloem loading in these C4 species. C4 photosynthesis, gene duplication, gene families, parallel evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Evolution of C2H2-zinc finger genes and subfamilies in mammals: Species-specific duplication and loss of clusters, genes and effector domains

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    Aubry Muriel

    2008-06-01

    Full Text Available Abstract Background C2H2 zinc finger genes (C2H2-ZNF constitute the largest class of transcription factors in humans and one of the largest gene families in mammals. Often arranged in clusters in the genome, these genes are thought to have undergone a massive expansion in vertebrates, primarily by tandem duplication. However, this view is based on limited datasets restricted to a single chromosome or a specific subset of genes belonging to the large KRAB domain-containing C2H2-ZNF subfamily. Results Here, we present the first comprehensive study of the evolution of the C2H2-ZNF family in mammals. We assembled the complete repertoire of human C2H2-ZNF genes (718 in total, about 70% of which are organized into 81 clusters across all chromosomes. Based on an analysis of their N-terminal effector domains, we identified two new C2H2-ZNF subfamilies encoding genes with a SET or a HOMEO domain. We searched for the syntenic counterparts of the human clusters in other mammals for which complete gene data are available: chimpanzee, mouse, rat and dog. Cross-species comparisons show a large variation in the numbers of C2H2-ZNF genes within homologous mammalian clusters, suggesting differential patterns of evolution. Phylogenetic analysis of selected clusters reveals that the disparity in C2H2-ZNF gene repertoires across mammals not only originates from differential gene duplication but also from gene loss. Further, we discovered variations among orthologs in the number of zinc finger motifs and association of the effector domains, the latter often undergoing sequence degeneration. Combined with phylogenetic studies, physical maps and an analysis of the exon-intron organization of genes from the SCAN and KRAB domains-containing subfamilies, this result suggests that the SCAN subfamily emerged first, followed by the SCAN-KRAB and finally by the KRAB subfamily. Conclusion Our results are in agreement with the "birth and death hypothesis" for the evolution of

  11. Internal tandem duplications in the Flt3-gene in human acute myeloid leukemia

    NARCIS (Netherlands)

    W.J.C. Rombouts

    2004-01-01

    textabstractIn the process of hematopoietic development errors may occur, resulting in the aber¬rant activation of (proto-)oncogenes and inactivation of tumor-suppressor genes. This aberrant gene expression may finally result in leukemia, a neoplastic disorder in which immature hematopoietic cells a

  12. Phylogenetic relationships among Perissodactyla: secretoglobin 1A1 gene duplication and triplication in the Equidae family.

    Science.gov (United States)

    Côté, Olivier; Viel, Laurent; Bienzle, Dorothee

    2013-12-01

    Secretoglobin family 1A member 1 (SCGB 1A1) is a small anti-inflammatory and immunomodulatory protein that is abundantly secreted in airway surface fluids. We recently reported the existence of three distinct SCGB1A1 genes in the domestic horse genome as opposed to the single gene copy consensus present in other mammals. The origin of SCGB1A1 gene triplication and the evolutionary relationship of the three genes amongst Equidae family members are unknown. For this study, SCGB1A1 genomic data were collected from various Equus individuals including E. caballus, E. przewalskii, E. asinus, E. grevyi, and E. quagga. Three SCGB1A1 genes in E. przewalskii, two SCGB1A1 genes in E. asinus, and a single SCGB1A1 gene in E. grevyi and E. quagga were identified. Sequence analysis revealed that the non-synonymous nucleotide substitutions between the different equid genes coded for 17 amino acid changes. Most of these changes localized to the SCGB 1A1 central cavity that binds hydrophobic ligands, suggesting that this area of SCGB 1A1 evolved to accommodate diverse molecular interactions. Three-dimensional modeling of the proteins revealed that the size of the SCGB 1A1 central cavity is larger than that of SCGB 1A1A. Altogether, these findings suggest that evolution of the SCGB1A1 gene may parallel the separation of caballine and non-caballine species amongst Equidae, and may indicate an expansion of function for SCGB1A1 gene products. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Specific duplication and dorsoventrally asymmetric expression patterns of Cycloidea-like genes in zygomorphic species of Ranunculaceae.

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    Florian Jabbour

    Full Text Available Floral bilateral symmetry (zygomorphy has evolved several times independently in angiosperms from radially symmetrical (actinomorphic ancestral states. Homologs of the Antirrhinum majus Cycloidea gene (Cyc have been shown to control floral symmetry in diverse groups in core eudicots. In the basal eudicot family Ranunculaceae, there is a single evolutionary transition from actinomorphy to zygomorphy in the stem lineage of the tribe Delphinieae. We characterized Cyc homologs in 18 genera of Ranunculaceae, including the four genera of Delphinieae, in a sampling that represents the floral morphological diversity of this tribe, and reconstructed the evolutionary history of this gene family in Ranunculaceae. Within each of the two RanaCyL (Ranunculaceae Cycloidea-like lineages previously identified, an additional duplication possibly predating the emergence of the Delphinieae was found, resulting in up to four gene copies in zygomorphic species. Expression analyses indicate that the RanaCyL paralogs are expressed early in floral buds and that the duration of their expression varies between species and paralog class. At most one RanaCyL paralog was expressed during the late stages of floral development in the actinomorphic species studied whereas all paralogs from the zygomorphic species were expressed, composing a species-specific identity code for perianth organs. The contrasted asymmetric patterns of expression observed in the two zygomorphic species is discussed in relation to their distinct perianth architecture.

  14. Gallbladder duplication

    Directory of Open Access Journals (Sweden)

    Yagan Pillay

    2015-01-01

    Conclusion: Duplication of the gallbladder is a rare congenital abnormality, which requires special attention to the biliary ductal and arterial anatomy. Laparoscopic cholecystectomy with intraoperative cholangiography is the appropriate treatment in a symptomatic gallbladder. The removal of an asymptomatic double gallbladder remains controversial.

  15. Xq13.2q21.1 duplication encompassing the ATRX gene in a man with mental retardation, minor facial and genital anomalies, short stature and broad thorax.

    NARCIS (Netherlands)

    Lugtenberg, D.; Brouwer, A.P.M. de; Oudakker, A.R.; Pfundt, R.P.; Hamel, B.C.J.; Bokhoven, H. van; Bongers, E.M.H.F.

    2009-01-01

    In a man with severe mental retardation, minor facial and genital anomalies, disproportionate short stature and a broad thorax, we identified a de novo Xq13.2q21.1 duplication by array CGH. This 7 Mb duplication encompasses 23 known genes, including the X-linked mental retardation (XLMR) genes ATRX

  16. MARCH5 gene is duplicated in rainbow trout, but only fish-specific gene copy is up-regulated after VHSV infection.

    Science.gov (United States)

    Rebl, Alexander; Köbis, Judith M; Fischer, Uwe; Takizawa, Fumio; Verleih, Marieke; Wimmers, Klaus; Goldammer, Tom

    2011-12-01

    Ubiquitination regulates the activity, stability, and localization of a wide variety of proteins. Several mammalian MARCH ubiquitin E3 ligase proteins have been suggested to control cell surface immunoreceptors. The mitochondrial protein MARCH5 is a positive regulator of Toll-like receptor 7-mediated NF-κB activation in mammals. In the present study, duplicated MARCH5-like cDNA sequences were isolated from rainbow trout (Oncorhynchus mykiss) comprising open reading frames of 882 bp (MARCH5A) and 885 bp (MARCH5B), respectively. Trout MARCH5A and MARCH5B-encoding sequences share only 65% sequence identity. Phylogenetic analyses including an additionally isolated MARCH5-like sequence from whitefish (Coregonus maraena) suggest that teleosts possess an additional MARCH5 gene copy resulting from a fish-specific whole genome duplication. Coding sequences of MARCH5A and MARCH5B genes from trout are distributed over six exons. Hypothetical MARCH5 proteins from trout comprise four transmembrane helices and a single motif similar to a RING variant domain (RINGv) including eight highly conserved cysteine and histidine residues. A 'reverse-northern blot' analysis revealed furthermore a MARCH5B Δexon5 transcript variant. Both MARCH5 genes from trout show a strain-, tissue- and cell-specific expression profile indicating different functional roles. Fish-specific MARCH5A gene for instance might be involved in defense mechanisms, since in vivo-challenge with the viral pathogen VHSV caused a significant 1.7-fold elevated copy number of the respective gene in gills four days after infection, whereas MARCH5B transcript level did not increase.

  17. Creation of Mice Bearing a Partial Duplication of HPRT Gene Marked with a GFP Gene and Detection of Revertant Cells In Situ as GFP-Positive Somatic Cells.

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    Asao Noda

    Full Text Available It is becoming clear that apparently normal somatic cells accumulate mutations. Such accumulations or propagations of mutant cells are thought to be related to certain diseases such as cancer. To better understand the nature of somatic mutations, we developed a mouse model that enables in vivo detection of rare genetically altered cells via GFP positive cells. The mouse model carries a partial duplication of 3' portion of X-chromosomal HPRT gene and a GFP gene at the end of the last exon. In addition, although HPRT gene expression was thought ubiquitous, the expression level was found insufficient in vivo to make the revertant cells detectable by GFP positivity. To overcome the problem, we replaced the natural HPRT-gene promoter with a CAG promoter. In such animals, termed HPRT-dup-GFP mouse, losing one duplicated segment by crossover between the two sister chromatids or within a single molecule of DNA reactivates gene function, producing hybrid HPRT-GFP proteins which, in turn, cause the revertant cells to be detected as GFP-positive cells in various tissues. Frequencies of green mutant cells were measured using fixed and frozen sections (liver and pancreas, fixed whole mount (small intestine, or by means of flow cytometry (unfixed splenocytes. The results showed that the frequencies varied extensively among individuals as well as among tissues. X-ray exposure (3 Gy increased the frequency moderately (~2 times in the liver and small intestine. Further, in two animals out of 278 examined, some solid tissues showed too many GFP-positive cells to score (termed extreme jackpot mutation. Present results illustrated a complex nature of somatic mutations occurring in vivo. While the HPRT-dup-GFP mouse may have a potential for detecting tissue-specific environmental mutagens, large inter-individual variations of mutant cell frequency cause the results unstable and hence have to be reduced. This future challenge will likely involve lowering the

  18. Host mitochondrial association evolved in the human parasite Toxoplasma gondii via neofunctionalization of a gene duplicate

    Science.gov (United States)

    In Toxoplasma gondii, an intracellular parasite of humans and other warm-blooded animals, the ability to associate with host mitochondria (HMA) is driven by a locally expanded gene family that encodes multiple mitochondrial association factor 1 (MAF1) proteins. The importance of copy number in the e...

  19. Characterization of the novel duplicated PRLR gene at the late-feathering K locus in Lohmann chickens.

    Science.gov (United States)

    Bu, Guixian; Huang, Guian; Fu, Hao; Li, Juan; Huang, Simiao; Wang, Yajun

    2013-10-01

    A partial duplication of the prolactin (PRL) receptor gene (designated as dPRLR) has been identified at the late-feathering (LF) K locus on chromosome Z of some chicken strains recently, implying that dPRLR is probably a candidate gene associated with LF development in chickens. However, little is known about the structure, functionality, and spatiotemporal expression of the dPRLR gene in chickens. In this study, using 3'-RACE and RT-PCR, the full-length cDNA of the dPRLR obtained from the kidneys of male Lohmann layer chickens carrying a K allele was cloned. The cloned dPRLR is predicted to encode a membrane-spanning receptor of 683 amino acids, which is nearly identical to the original PRLR, except for its lack of a 149-amino acid C-terminal tail. Using a 5× STAT5-Luciferase reporter system and western blot analysis, we demonstrated that dPRLR expressed in HepG2 cells could be potently activated by chicken PRL and functionally coupled to the intracellular STAT5 signaling pathway, suggesting that dPRLR may function as a novel receptor for PRL. RT-PCR assays revealed that similar to the original PRLR gene, dPRLR mRNA is widely expressed in all embryonic and adult tissues examined including the skin of male Lohmann chickens with a K allele. These findings, together with the expression of PRL mRNA detected in the skin of embryos at embryonic day 20 and 1-week-old chicks, suggest that skin-expressed dPRLR and PRLR, together with plasma and skin-derived PRL, may be involved in the control of the LF development of chicks at hatching. Moreover, the wide tissue expression of dPRLR implies that dPRLR may regulate other physiological processes of chickens carrying the K allele.

  20. Structure and characterisation of a duplicated human alpha 1 acid glycoprotein gene.

    Science.gov (United States)

    Merritt, C M; Board, P G

    1988-06-15

    Human alpha 1-acid glycoprotein (AGP), also known as orosomucoid, is a major acute-phase plasma protein. The amino acid sequence of AGP, which was determined by sequencing from protein isolated from pooled plasma, contained amino acid substitutions in 21 different positions. Genomic and cDNA clones which correspond to one of the possible amino acid sequences have been previously reported. In this paper we present the complete nucleotide sequence of a second gene, AGP2 which is located approx. 3.3 kb downstream from AGP1. The derived amino acid sequence of AGP2 contains 19 of the possible alternative amino acid substitutions as well as two additional differences. It is clear from the results presented here that the AGP in human plasma is the product of two separate gene loci.

  1. A search for RNA insertions and NS3 gene duplication in the genome of cytopathic isolates of bovine viral diarrhea virus

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    V.L. Quadros

    2006-07-01

    Full Text Available Calves born persistently infected with non-cytopathic bovine viral diarrhea virus (ncpBVDV frequently develop a fatal gastroenteric illness called mucosal disease. Both the original virus (ncpBVDV and an antigenically identical but cytopathic virus (cpBVDV can be isolated from animals affected by mucosal disease. Cytopathic BVDVs originate from their ncp counterparts by diverse genetic mechanisms, all leading to the expression of the non-structural polypeptide NS3 as a discrete protein. In contrast, ncpBVDVs express only the large precursor polypeptide, NS2-3, which contains the NS3 sequence within its carboxy-terminal half. We report here the investigation of the mechanism leading to NS3 expression in 41 cpBVDV isolates. An RT-PCR strategy was employed to detect RNA insertions within the NS2-3 gene and/or duplication of the NS3 gene, two common mechanisms of NS3 expression. RT-PCR amplification revealed insertions in the NS2-3 gene of three cp isolates, with the inserts being similar in size to that present in the cpBVDV NADL strain. Sequencing of one such insert revealed a 296-nucleotide sequence with a central core of 270 nucleotides coding for an amino acid sequence highly homologous (98% to the NADL insert, a sequence corresponding to part of the cellular J-Domain gene. One cpBVDV isolate contained a duplication of the NS3 gene downstream from the original locus. In contrast, no detectable NS2-3 insertions or NS3 gene duplications were observed in the genome of 37 cp isolates. These results demonstrate that processing of NS2-3 without bulk mRNA insertions or NS3 gene duplications seems to be a frequent mechanism leading to NS3 expression and BVDV cytopathology.

  2. Functional characterization of duplicated B-class MADS-box genes in Japanese gentian.

    Science.gov (United States)

    Nakatsuka, Takashi; Saito, Misa; Nishihara, Masahiro

    2016-04-01

    The heterodimer formation between B-class MADS-box proteins of GsAP3a and GsPI2 proteins plays a core role for petal formation in Japanese gentian plants. We previously isolated six B-class MADS-box genes (GsAP3a, GsAP3b, GsTM6, GsPI1, GsPI2, and GsPI3) from Japanese gentian (Gentiana scabra). To study the roles of these MADS-box genes in determining floral organ identities, we investigated protein-protein interactions among them and produced transgenic Arabidopsis and gentian plants overexpressing GsPI2 alone or in combination with GsAP3a or GsTM6. Yeast two-hybrid and bimolecular fluorescence complementation analyses revealed that among the GsPI proteins, GsPI2 interacted with both GsAP3a and GsTM6, and that these heterodimers were localized to the nuclei. The heterologous expression of GsPI2 partially converted sepals into petaloid organs in transgenic Arabidopsis, and this petaloid conversion phenomenon was accelerated by combined expression with GsAP3a but not with GsTM6. In contrast, there were no differences in morphology between vector-control plants and transgenic Arabidopsis plants expressing GsAP3a or GsTM6 alone. Transgenic gentian ectopically expressing GsPI2 produced an elongated tubular structure that consisted of an elongated petaloid organ in the first whorl and stunted inner floral organs. These results imply that the heterodimer formation between GsPI2 and GsAP3a plays a core role in determining petal and stamen identities in Japanese gentian, but other B-function genes might be important for the complete development of petal organs.

  3. 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.

  4. Identification of Ohnolog Genes Originating from Whole Genome Duplication in Early Vertebrates, Based on Synteny Comparison across Multiple Genomes.

    Directory of Open Access Journals (Sweden)

    Param Priya Singh

    2015-07-01

    Full Text Available 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.

  5. Evolution of C, D and S-type cystatins in mammals: an extensive gene duplication in primates.

    Science.gov (United States)

    de Sousa-Pereira, Patrícia; Abrantes, Joana; Pinheiro, Ana; Colaço, Bruno; Vitorino, Rui; Esteves, Pedro J

    2014-01-01

    Cystatins are a family of inhibitors of cysteine peptidases that comprises the salivary cystatins (D and S-type cystatins) and cystatin C. These cystatins are encoded by a multigene family (CST3, CST5, CST4, CST1 and CST2) organized in tandem in the human genome. Their presence and functional importance in human saliva has been reported, however the distribution of these proteins in other mammals is still unclear. Here, we performed a proteomic analysis of the saliva of several mammals and studied the evolution of this multigene family. The proteomic analysis detected S-type cystatins (S, SA, and SN) in human saliva and cystatin D in rat saliva. The evolutionary analysis showed that the cystatin C encoding gene is present in species of the most representative mammalian groups, i.e. Artiodactyla, Rodentia, Lagomorpha, Carnivora and Primates. On the other hand, D and S-type cystatins are mainly retrieved from Primates, and especially the evolution of S-type cystatins seems to be a dynamic process as seen in Pongo abelii genome where several copies of CST1-like gene (cystatin SN) were found. In Rodents, a group of cystatins previously identified as D and S has also evolved. Despite the high divergence of the amino acid sequence, their position in the phylogenetic tree and their genome organization suggests a common origin with those of the Primates. These results suggest that the D and S type cystatins have emerged before the mammalian radiation and were retained only in Primates and Rodents. Although the mechanisms driving the evolution of cystatins are unknown, it seems to be a dynamic process with several gene duplications evolving according to the birth-and-death model of evolution. The factors that led to the appearance of a group of saliva-specific cystatins in Primates and its rapid evolution remain undetermined, but may be associated with an adaptive advantage.

  6. Evolution of C, D and S-type cystatins in mammals: an extensive gene duplication in primates.

    Directory of Open Access Journals (Sweden)

    Patrícia de Sousa-Pereira

    Full Text Available Cystatins are a family of inhibitors of cysteine peptidases that comprises the salivary cystatins (D and S-type cystatins and cystatin C. These cystatins are encoded by a multigene family (CST3, CST5, CST4, CST1 and CST2 organized in tandem in the human genome. Their presence and functional importance in human saliva has been reported, however the distribution of these proteins in other mammals is still unclear. Here, we performed a proteomic analysis of the saliva of several mammals and studied the evolution of this multigene family. The proteomic analysis detected S-type cystatins (S, SA, and SN in human saliva and cystatin D in rat saliva. The evolutionary analysis showed that the cystatin C encoding gene is present in species of the most representative mammalian groups, i.e. Artiodactyla, Rodentia, Lagomorpha, Carnivora and Primates. On the other hand, D and S-type cystatins are mainly retrieved from Primates, and especially the evolution of S-type cystatins seems to be a dynamic process as seen in Pongo abelii genome where several copies of CST1-like gene (cystatin SN were found. In Rodents, a group of cystatins previously identified as D and S has also evolved. Despite the high divergence of the amino acid sequence, their position in the phylogenetic tree and their genome organization suggests a common origin with those of the Primates. These results suggest that the D and S type cystatins have emerged before the mammalian radiation and were retained only in Primates and Rodents. Although the mechanisms driving the evolution of cystatins are unknown, it seems to be a dynamic process with several gene duplications evolving according to the birth-and-death model of evolution. The factors that led to the appearance of a group of saliva-specific cystatins in Primates and its rapid evolution remain undetermined, but may be associated with an adaptive advantage.

  7. Molecular cloning and expression analysis of duplicated polyphenol oxidase genes reveal their functional differentiations in sorghum.

    Science.gov (United States)

    Yan, Song; Li, Sujuan; Zhai, Guowei; Lu, Ping; Deng, Hui; Zhu, Shan; Huang, Renliang; Shao, Jianfeng; Tao, Yuezhi; Zou, Guihua

    2017-10-01

    Polyphenol oxidase (PPO) is believed to play a role in plant growth, reproduction, and resistance to pathogens and pests. PPO causes browning of grains in cereals. In this study, genetic mapping of sorghum grain for phenol color reaction (PHR) was performed using a recombinant inbred line population. Only one locus was detected between SSR markers SM06072 and Xtxp176 on chromosome 6. Two linked orthologous genes (Sb06PPO1 and Sb06PPO2) within the mapped region were discovered and cloned. Transformation experiments using Nipponbare (a PHR negative rice cultivar) showed that Sb06PPO1 from LTR108 and two Sb06PPO2 alleles from both varieties could complement Nipponbare, whereas Sb06PPO1 from 654 could not. Subsequent quantitative real-time PCR (qPCR) experiments showed that Sb06PPO1 and Sb06PPO2 functioned diversely, Sb06PPO1 was mainly expressed in young panicles before flowering. Sb06PPO2 was strongly expressed in flowering panicles, especially in hulls and branches at filling stage. Moreover, the expression of Sb06PPO1 was found to be significantly up-regulated by exogenous ABA and salt, whereas Sb06PPO2 was not changed significantly, further demonstrating functional differentiation between the two genes. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. AMID: autonomous modeler of intragenic duplication.

    Science.gov (United States)

    Kummerfeld, Sarah K; Weiss, Anthony S; Fekete, Alan; Jermiin, Lars S

    2003-01-01

    Intragenic duplication is an evolutionary process where segments of a gene become duplicated. While there has been much research into whole-gene or domain duplication, there have been very few studies of non-tandem intragenic duplication. The identification of intragenically replicated sequences may provide insight into the evolution of proteins, helping to link sequence data with structure and function. This paper describes a tool for autonomously modelling intragenic duplication. AMID provides: identification of modularly repetitive genes; an algorithm for identifying repeated modules; and a scoring system for evaluating the modules' similarity. An evaluation of the algorithms and use cases are presented.

  9. Primate segmental duplication creates novel promoters for the LRRC37 gene family within the 17q21.31 inversion polymorphism region

    Science.gov (United States)

    Bekpen, Cemalettin; Tastekin, Ibrahim; Siswara, Priscillia; Akdis, Cezmi A.; Eichler, Evan E.

    2012-01-01

    The LRRC37 gene family maps to a complex region of the human genome and has been subjected to multiple rounds of segmental duplication. We investigate the expression and regulation of this gene family in multiple tissues and organisms and show a testis-specific expression of this gene family in mouse but a more ubiquitous pattern of expression among primates. Evolutionary and phylogenetic analyses support a model in which new alternative promoters have been acquired during primate evolution. We identify two promoters, Cl8 and particularly Cl3, both of which are highly active in the cerebellum and fetal brain in human and have been duplicated from a promoter region of two unrelated genes, BPTF and DND1, respectively. Two of these more broadly expressed gene family members, LRRC37A1 and A4, define the boundary of a common human inversion polymorphism mapping to chromosome 17q21.31 (the MAPT locus)—a region associated with risk for frontal temporal dementia, Parkinsonism, and intellectual disability. We propose that the regulation of the LRRC37 family occurred in a stepwise manner, acquiring foreign promoters from BPTF and DND1 via segmental duplication. This unusual evolutionary trajectory altered the regulation of the LRRC37 family, leading to increased expression in the fetal brain and cerebellum. PMID:22419166

  10. Phylogenetic analysis of eukaryotic NEET proteins uncovers a link between a key gene duplication event and the evolution of vertebrates

    Science.gov (United States)

    Inupakutika, Madhuri A.; Sengupta, Soham; Nechushtai, Rachel; Jennings, Patricia A.; Onuchic, Jose’ N.; Azad, Rajeev K.; Padilla, Pamela; Mittler, Ron

    2017-02-01

    NEET proteins belong to a unique family of iron-sulfur proteins in which the 2Fe-2S cluster is coordinated by a CDGSH domain that is followed by the “NEET” motif. They are involved in the regulation of iron and reactive oxygen metabolism, and have been associated with the progression of diabetes, cancer, aging and neurodegenerative diseases. Despite their important biological functions, the evolution and diversification of eukaryotic NEET proteins are largely unknown. Here we used the three members of the human NEET protein family (CISD1, mitoNEET; CISD2, NAF-1 or Miner 1; and CISD3, Miner2) as our guides to conduct a phylogenetic analysis of eukaryotic NEET proteins and their evolution. Our findings identified the slime mold Dictyostelium discoideum’s CISD proteins as the closest to the ancient archetype of eukaryotic NEET proteins. We further identified CISD3 homologs in fungi that were previously reported not to contain any NEET proteins, and revealed that plants lack homolog(s) of CISD3. Furthermore, our study suggests that the mammalian NEET proteins, mitoNEET (CISD1) and NAF-1 (CISD2), emerged via gene duplication around the origin of vertebrates. Our findings provide new insights into the classification and expansion of the NEET protein family, as well as offer clues to the diverged functions of the human mitoNEET and NAF-1 proteins.

  11. RNA-Mediated Gene Duplication and Retroposons: Retrogenes, LINEs, SINEs, and Sequence Specificity

    Science.gov (United States)

    2013-01-01

    A substantial number of “retrogenes” that are derived from the mRNA of various intron-containing genes have been reported. A class of mammalian retroposons, long interspersed element-1 (LINE1, L1), has been shown to be involved in the reverse transcription of retrogenes (or processed pseudogenes) and non-autonomous short interspersed elements (SINEs). The 3′-end sequences of various SINEs originated from a corresponding LINE. As the 3′-untranslated regions of several LINEs are essential for retroposition, these LINEs presumably require “stringent” recognition of the 3′-end sequence of the RNA template. However, the 3′-ends of mammalian L1s do not exhibit any similarity to SINEs, except for the presence of 3′-poly(A) repeats. Since the 3′-poly(A) repeats of L1 and Alu SINE are critical for their retroposition, L1 probably recognizes the poly(A) repeats, thereby mobilizing not only Alu SINE but also cytosolic mRNA. Many flowering plants only harbor L1-clade LINEs and a significant number of SINEs with poly(A) repeats, but no homology to the LINEs. Moreover, processed pseudogenes have also been found in flowering plants. I propose that the ancestral L1-clade LINE in the common ancestor of green plants may have recognized a specific RNA template, with stringent recognition then becoming relaxed during the course of plant evolution. PMID:23984183

  12. RNA-Mediated Gene Duplication and Retroposons: Retrogenes, LINEs, SINEs, and Sequence Specificity

    Directory of Open Access Journals (Sweden)

    Kazuhiko Ohshima

    2013-01-01

    Full Text Available A substantial number of “retrogenes” that are derived from the mRNA of various intron-containing genes have been reported. A class of mammalian retroposons, long interspersed element-1 (LINE1, L1, has been shown to be involved in the reverse transcription of retrogenes (or processed pseudogenes and non-autonomous short interspersed elements (SINEs. The -end sequences of various SINEs originated from a corresponding LINE. As the -untranslated regions of several LINEs are essential for retroposition, these LINEs presumably require “stringent” recognition of the -end sequence of the RNA template. However, the -ends of mammalian L1s do not exhibit any similarity to SINEs, except for the presence of -poly(A repeats. Since the -poly(A repeats of L1 and Alu SINE are critical for their retroposition, L1 probably recognizes the poly(A repeats, thereby mobilizing not only Alu SINE but also cytosolic mRNA. Many flowering plants only harbor L1-clade LINEs and a significant number of SINEs with poly(A repeats, but no homology to the LINEs. Moreover, processed pseudogenes have also been found in flowering plants. I propose that the ancestral L1-clade LINE in the common ancestor of green plants may have recognized a specific RNA template, with stringent recognition then becoming relaxed during the course of plant evolution.

  13. Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes.

    OpenAIRE

    Tsuchida, S.; Matsusaka, T; Chen, X; Okubo, S.; Niimura, F; Nishimura, H.; Fogo, A.; Utsunomiya, H.; Inagami, T; Ichikawa, I

    1998-01-01

    Rodents are the unique species carrying duplicated angiotensin (Ang) type 1 (AT1) receptor genes, Agtr1a and Agtr1b. After separately generating Agtr1a and Agtr1b null mutant mice by gene targeting, we produced double mutant mice homozygous for both Agtr1a and Agtr1b null mutation (Agtr1a-/-; Agtr1b-/-) by mating the single gene mutants. Agtr1a-/-, Agtr1b-/- mice are characterized by normal in utero survival but decreased ex utero survival rate. After birth they are characterized by low body ...

  14. 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.

  15. Opposing phenotypes in mice with Smith-Magenis deletion and Potocki-Lupski duplication syndromes suggest gene dosage effects on fluid consumption behavior.

    Science.gov (United States)

    Heck, Detlef H; Gu, Wenli; Cao, Ying; Qi, Shuhua; Lacaria, Melanie; Lupski, James R

    2012-11-01

    A quantitative long-term fluid consumption and fluid-licking assay was performed in two mouse models with either an ∼2 Mb genomic deletion, Df(11)17, or the reciprocal duplication copy number variation (CNV), Dp(11)17, analogous to the human genomic rearrangements causing either Smith-Magenis syndrome [SMS; OMIM #182290] or Potocki-Lupski syndrome [PTLS; OMIM #610883], respectively. Both mouse strains display distinct quantitative alterations in fluid consumption compared to their wild-type littermates; several of these changes are diametrically opposing between the two chromosome engineered mouse models. Mice with duplication versus deletion showed longer versus shorter intervals between visits to the waterspout, generated more versus less licks per visit and had higher versus lower variability in the number of licks per lick-burst as compared to their respective wild-type littermates. These findings suggest that copy number variation can affect long-term fluid consumption behavior in mice. Other behavioral differences were unique for either the duplication or deletion mutants; the deletion CNV resulted in increased variability of the licking rhythm, and the duplication CNV resulted in a significant slowing of the licking rhythm. Our findings document a readily quantitated complex behavioral response that can be directly and reciprocally influenced by a gene dosage effect.

  16. Gallin; an antimicrobial peptide member of a new avian defensin family, the ovodefensins, has been subject to recent gene duplication

    Directory of Open Access Journals (Sweden)

    Kalina Jiri

    2010-03-01

    Full Text Available Abstract Background Egg white must provide nutrients and protection to the developing avian embryo. One way in which this is achieved is an arsenal of antimicrobial proteins and peptides which are essentially extensions of the innate immune system. Gallin is a recently identified member of a family of peptides that are found in egg white. The function of this peptide family has not been identified and they are potentially antimicrobial. Results We have confirmed that there are at least 3 forms of the gallin gene in the chicken genome in 3 separate lines of chicken, all the forms are expressed in the tubular cells of the magnum region of the oviduct, consistent with its presence in egg white. mRNA expression levels are in the order 10,000 times greater in the magnum than the shell gland. The conservation between the multiple forms of gallin in the chicken genome compared with the conservation between gallin and other avian gallin like peptides, suggests that the gene duplication has occurred relatively recently in the chicken lineage. The gallin peptide family contains a six cysteine motif (C-X5-C-X3-C-X11-C-X3-C-C found in all defensins, and is most closely related to avian beta-defensins, although the cysteine spacing differs. Further support for the classification comes from the presence of a glycine at position 10 in the 41 amino acid peptide. Recombinant gallin inhibited the growth of Escherischia coli (E. coli at a concentration of 0.25 μM confirming it as part of the antimicrobial innate immune system in avian species. Conclusions The relatively recent evolution of multiple forms of a member of a new defensin related group of peptides that we have termed ovodefensins, may be an adaptation to increase expression or the first steps in divergent evolution of the gene in chickens. The potent antimicrobial activity of the peptide against E. coli increases our understanding of the antimicrobial strategies of the avian innate immune system

  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. Comparative analysis of Phytophthora genes encoding secreted proteins reveals conserved synteny and lineage-specific gene duplications and deletions

    NARCIS (Netherlands)

    Jiang, R.H.Y.; Tyler, B.M.; Govers, F.

    2006-01-01

    Comparative analysis of two Phytophthora genomes revealed overall colinearity in four genomic regions consisting of a 1.5-Mb sequence of Phytophthora sojae and a 0.9-Mb sequence of R ramorum. In these regions with conserved synteny, the gene order is largely similar; however, genome rearrangements a

  19. Sequencing of Pax6 loci from the elephant shark reveals a family of Pax6 genes in vertebrate genomes, forged by ancient duplications and divergences.

    Directory of Open Access Journals (Sweden)

    Vydianathan Ravi

    Full Text Available Pax6 is a developmental control gene essential for eye development throughout the animal kingdom. In addition, Pax6 plays key roles in other parts of the CNS, olfactory system, and pancreas. In mammals a single Pax6 gene encoding multiple isoforms delivers these pleiotropic functions. Here we provide evidence that the genomes of many other vertebrate species contain multiple Pax6 loci. We sequenced Pax6-containing BACs from the cartilaginous elephant shark (Callorhinchus milii and found two distinct Pax6 loci. Pax6.1 is highly similar to mammalian Pax6, while Pax6.2 encodes a paired-less Pax6. Using synteny relationships, we identify homologs of this novel paired-less Pax6.2 gene in lizard and in frog, as well as in zebrafish and in other teleosts. In zebrafish two full-length Pax6 duplicates were known previously, originating from the fish-specific genome duplication (FSGD and expressed in divergent patterns due to paralog-specific loss of cis-elements. We show that teleosts other than zebrafish also maintain duplicate full-length Pax6 loci, but differences in gene and regulatory domain structure suggest that these Pax6 paralogs originate from a more ancient duplication event and are hence renamed as Pax6.3. Sequence comparisons between mammalian and elephant shark Pax6.1 loci highlight the presence of short- and long-range conserved noncoding elements (CNEs. Functional analysis demonstrates the ancient role of long-range enhancers for Pax6 transcription. We show that the paired-less Pax6.2 ortholog in zebrafish is expressed specifically in the developing retina. Transgenic analysis of elephant shark and zebrafish Pax6.2 CNEs with homology to the mouse NRE/Pα internal promoter revealed highly specific retinal expression. Finally, morpholino depletion of zebrafish Pax6.2 resulted in a "small eye" phenotype, supporting a role in retinal development. In summary, our study reveals that the pleiotropic functions of Pax6 in vertebrates are served by

  20. Alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora arose from duplication of a dual-functional predecessor of mitochondrial origin.

    Science.gov (United States)

    Chang, Chia-Pei; Tseng, Yi-Kuan; Ko, Chou-Yuan; Wang, Chien-Chia

    2012-01-01

    In eukaryotes, the cytoplasmic and mitochondrial forms of a given aminoacyl-tRNA synthetase (aaRS) are typically encoded by two orthologous nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. We herein report a novel scenario of aaRS evolution in yeast. While all other yeast species studied possess a single nuclear gene encoding both forms of alanyl-tRNA synthetase (AlaRS), Vanderwaltozyma polyspora, a yeast species descended from the same whole-genome duplication event as Saccharomyces cerevisiae, contains two distinct nuclear AlaRS genes, one specifying the cytoplasmic form and the other its mitochondrial counterpart. The protein sequences of these two isoforms are very similar to each other. The isoforms are actively expressed in vivo and are exclusively localized in their respective cellular compartments. Despite the presence of a promising AUG initiator candidate, the gene encoding the mitochondrial form is actually initiated from upstream non-AUG codons. A phylogenetic analysis further revealed that all yeast AlaRS genes, including those in V. polyspora, are of mitochondrial origin. These findings underscore the possibility that contemporary AlaRS genes in V. polyspora arose relatively recently from duplication of a dual-functional predecessor of mitochondrial origin.

  1. Diversification of genes encoding granule-bound starch synthase in monocots and dicots is marked by multiple genome-wide duplication events.

    Directory of Open Access Journals (Sweden)

    Jun Cheng

    Full Text Available Starch is one of the major components of cereals, tubers, and fruits. Genes encoding granule-bound starch synthase (GBSS, which is responsible for amylose synthesis, have been extensively studied in cereals but little is known about them in fruits. Due to their low copy gene number, GBSS genes have been used to study plant phylogenetic and evolutionary relationships. In this study, GBSS genes have been isolated and characterized in three fruit trees, including apple, peach, and orange. Moreover, a comprehensive evolutionary study of GBSS genes has also been conducted between both monocots and eudicots. Results have revealed that genomic structures of GBSS genes in plants are conserved, suggesting they all have evolved from a common ancestor. In addition, the GBSS gene in an ancestral angiosperm must have undergone genome duplication ∼251 million years ago (MYA to generate two families, GBSSI and GBSSII. Both GBSSI and GBSSII are found in monocots; however, GBSSI is absent in eudicots. The ancestral GBSSII must have undergone further divergence when monocots and eudicots split ∼165 MYA. This is consistent with expression profiles of GBSS genes, wherein these profiles are more similar to those of GBSSII in eudicots than to those of GBSSI genes in monocots. In dicots, GBSSII must have undergone further divergence when rosids and asterids split from each other ∼126 MYA. Taken together, these findings suggest that it is GBSSII rather than GBSSI of monocots that have orthologous relationships with GBSS genes of eudicots. Moreover, diversification of GBSS genes is mainly associated with genome-wide duplication events throughout the evolutionary course of history of monocots and eudicots.

  2. Small Duplication of HPRT 1 Gene May Be Causative For Lesh-Nyhan Disease in Iranian Patients

    Directory of Open Access Journals (Sweden)

    Razieh BOROUJERDI

    2015-01-01

    Full Text Available How to Cite This Article: Boroujerdi R, Shariati M, Naddafnia H, Rezaei H. Small Duplication of HPRT 1 Gene May Be Causative For Lesh-Nyhan Disease in Iranian Patients. Iran J Child Neurol. 2015 Winter;9(1:103-106.AbstractDeficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT is a rare inborn error of purine metabolism and is characterized by uric acid overproduction along with a variety of neurological manifestations that depend on a degree of the enzymatic deficiency. Inheritance of HPRT deficiency is X-linked recessive; thus, males are generally more affected and heterozygous females are carriers (usually asymptomatic. Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. More than 300 mutations in the HPRT1 gene have been detected. Diagnosis can be based on clinical and biochemical findings as well as enzymatic and molecular testing. Molecular diagnosis is the best way as it allows for faster and more accurate carrier and prenatal diagnosis. In this report, a new small duplication in the HPRT1 gene was found by sequencing, which has yet to be reported.References Fu R, Jinnah HA. Genotype-Phenotype Correlations in Lesch-Nyhan Disease Moving Beyond The Gene. Journal of Biological Chemistry. 2012; 287(5:2997- 3008.Fontenelle LJ, Henderson JF. An enzymatic basis for the inability of erythrocytes to synthesize purine ribonucleotides de novo. Biochim Biophys Acta. 1969 Feb 18; 177(1:175-6. PubMed PMID: 5781193.Kelley WN, Wyngaardcn JB. Clinical syndromes associated with hypoxanthine guanine Phosphoribosyl transferase deficiency. In: J. B. Stanbury, J. B. Wyngaarden, D. S. Frederickson, J. L. Goldstein, M. S. Brown, editors. The Metabolic Basis of Inherited Disease. 5 ed. New York: McGraw Hill; 1983. p. 1115-43.Lesch M, Nyhan WL. A Familial Disorder of Uric Acid Metabolism and Central Nervous System Function. Am J Med. 1964 Apr; 36:561-70. PubMed PMID: 14142409.Christie R, Bay C, Kaufman IA

  3. Detecting long tandem duplications in genomic sequences

    Directory of Open Access Journals (Sweden)

    Audemard Eric

    2012-05-01

    Full Text Available Abstract Background Detecting duplication segments within completely sequenced genomes provides valuable information to address genome evolution and in particular the important question of the emergence of novel functions. The usual approach to gene duplication detection, based on all-pairs protein gene comparisons, provides only a restricted view of duplication. Results In this paper, we introduce ReD Tandem, a software using a flow based chaining algorithm targeted at detecting tandem duplication arrays of moderate to longer length regions, with possibly locally weak similarities, directly at the DNA level. On the A. thaliana genome, using a reference set of tandem duplicated genes built using TAIR,a we show that ReD Tandem is able to predict a large fraction of recently duplicated genes (dS  Conclusions ReD Tandem allows to identify large tandem duplications without any annotation, leading to agnostic identification of tandem duplications. This approach nicely complements the usual protein gene based which ignores duplications involving non coding regions. It is however inherently restricted to relatively recent duplications. By recovering otherwise ignored events, ReD Tandem gives a more comprehensive view of existing evolutionary processes and may also allow to improve existing annotations.

  4. Using paleogenomics to study the evolution of gene families: origin and duplication history of the relaxin family hormones and their receptors.

    Directory of Open Access Journals (Sweden)

    Sergey Yegorov

    Full Text Available Recent progress in the analysis of whole genome sequencing data has resulted in the emergence of paleogenomics, a field devoted to the reconstruction of ancestral genomes. Ancestral karyotype reconstructions have been used primarily to illustrate the dynamic nature of genome evolution. In this paper, we demonstrate how they can also be used to study individual gene families by examining the evolutionary history of relaxin hormones (RLN/INSL and relaxin family peptide receptors (RXFP. Relaxin family hormones are members of the insulin superfamily, and are implicated in the regulation of a variety of primarily reproductive and neuroendocrine processes. Their receptors are G-protein coupled receptors (GPCR's and include members of two distinct evolutionary groups, an unusual characteristic. Although several studies have tried to elucidate the origins of the relaxin peptide family, the evolutionary origin of their receptors and the mechanisms driving the diversification of the RLN/INSL-RXFP signaling systems in non-placental vertebrates has remained elusive. Here we show that the numerous vertebrate RLN/INSL and RXFP genes are products of an ancestral receptor-ligand system that originally consisted of three genes, two of which apparently trace their origins to invertebrates. Subsequently, diversification of the system was driven primarily by whole genome duplications (WGD, 2R and 3R followed by almost complete retention of the ligand duplicates in most vertebrates but massive loss of receptor genes in tetrapods. Interestingly, the majority of 3R duplicates retained in teleosts are potentially involved in neuroendocrine regulation. Furthermore, we infer that the ancestral AncRxfp3/4 receptor may have been syntenically linked to the AncRln-like ligand in the pre-2R genome, and show that syntenic linkages among ligands and receptors have changed dynamically in different lineages. This study ultimately shows the broad utility, with some caveats, of

  5. Molecular characterization and differential expression of two duplicated odorant receptor genes, AcerOr1 and AcerOr3, in Apis cerana cerana

    Indian Academy of Sciences (India)

    Huiting Zhao; Pengfei Gao; Haiyan Du; Weihua Ma; Songhao Tian; Yusuo Jiang

    2014-04-01

    Insects use olfaction to recognize a wide range of volatile cues, to locate food sources, mates, hosts and oviposition sites. These chemical volatiles are perceived by odorant receptors (ORs) expressed on the dendritic membrane of olfactory neurons, most of which are housed within the chemosensilla of antennae. Most insect ORs are tandemly arrayed on chromosomes and some of them are formed by gene duplication. Here, we identified a pair of duplicated Or genes, AcerOr1 and AcerOr3, from the antennae of the Asian honeybee, Apis cerana cerana, and reported their molecular characterization and temporal expression profiles. The results showed that these two genes shared high similarity both in sequence and the gene structure. Quantitative real-time PCR analysis of temporal expression pattern indicated that in drones the expression pattern of these two genes were very similar. The transcripts expressed weakly in larvae and pupae, then increased gradually in adults. In workers, the expression level of AcerOr1 changed more drastically and expressed higher than that of AcerOr3. However, both reached their highest expression level in one-day-old adults. In addition, the expression profiles between different sexes revealed that AcerOr3 appear to be expressed biased in male antennae. These results suggest that AcerOr1 may perceive odours of floral scents, while AcerOr3 may detect odours critical to male behaviour, such as the queen substance cues.

  6. Delineation of a new chromosome 20q11.2 duplication syndrome including the ASXL1 gene

    DEFF Research Database (Denmark)

    Avila, Magali; Kirchhoff, Eva Maria; Marle, Nathalie;

    2013-01-01

    We report on three males with de novo overlapping 7.5, 9.8, and 10 Mb duplication of chromosome 20q11.2. Together with another patient previously published in the literature with overlapping 20q11 microduplication, we show that such patients display common clinical features including metopic ridg...

  7. Phylogeny and diversification of B-function MADS-box genes in angiosperms: evolutionary and functional implications of a 260-million-year-old duplication.

    Science.gov (United States)

    Kim, Sangtae; Yoo, Mi-Jeong; Albert, Victor A; Farris, James S; Soltis, Pamela S; Soltis, Douglas E

    2004-12-01

    B-function MADS-box genes play crucial roles in floral development in model angiosperms. We reconstructed the structural and functional implications of B-function gene phylogeny in the earliest extant flowering plants based on analyses that include 25 new AP3 and PI sequences representing critical lineages of the basalmost angiosperms: Amborella, Nuphar (Nymphaeaceae), and Illicium (Austrobaileyales). The ancestral size of exon 5 in PI-homologues is 42 bp, typical of exon 5 in other plant MADS-box genes. This 42-bp length is found in PI-homologues from Amborella and Nymphaeaceae, successive sisters to all other angiosperms. Following these basalmost branches, a deletion occurred in exon 5, yielding a length of 30 bp, a condition that unites all other angiosperms. Several shared amino acid strings, including a prominent "DEAER" motif, are present in the AP3- and PI-homologues of Amborella. These may be ancestral motifs that were present before the duplication that yielded the AP3 and PI lineages and subsequently were modified after the divergence of Amborella. Other structural features were identified, including a motif that unites the previously described TM6 clade and a deletion in AP3-homologues that unites all Magnoliales. Phylogenetic analyses of AP3- and PI-homologues yielded gene trees that generally track organismal phylogeny as inferred by multigene data sets. With both AP3 and PI amino acid sequences, Amborella and Nymphaeaceae are sister to all other angiosperms. Using nonparametric rate smoothing (NPRS), we estimated that the duplication that produced the AP3 and PI lineages occurred approximately 260 mya (231-290). This places the duplication after the split between extant gymnosperms and angiosperms, but well before the oldest angiosperm fossils. A striking similarity in the multimer-signalling C domains of the Amborella proteins suggests the potential for the formation of unique transcription-factor complexes. The earliest angiosperms may have been

  8. Complete mtDNA sequences of two millipedes suggest a new model for mitochondrial gene rearrangements: Duplication and non-random loss

    Energy Technology Data Exchange (ETDEWEB)

    Lavrov, Dennis V.; Boore, Jeffrey L.; Brown, Wesley M.

    2001-11-08

    We determined the complete mtDNA sequences of the millipedes Narceus annularus and Thyropygus sp. (Arthropoda: Diplopoda) and identified in both genomes all 37 genes typical for metazoan mtDNA. The arrangement of these genes is identical in the two millipedes, but differs from that inferred to be ancestral for arthropods by the location of four genes/gene clusters. This novel gene arrangement is unusual for animal mtDNA, in that genes with opposite transcriptional polarities are clustered in the genome and the two clusters are separated by two non-coding regions. The only exception to this pattern is the gene for cysteine tRNA, which is located in the part of the genome that otherwise contains all genes with the opposite transcriptional polarity. We suggest that a mechanism involving complete mtDNA duplication followed by the loss of genes, predetermined by their transcriptional polarity and location in the genome, could generate this gene arrangement from the one ancestral for arthropods. The proposed mechanism has important implications for phylogenetic inferences that are drawn on the basis of gene arrangement comparisons.

  9. Whole genome sequencing of field isolates reveals a common duplication of the Duffy binding protein gene in Malagasy Plasmodium vivax strains.

    Directory of Open Access Journals (Sweden)

    Didier Menard

    2013-11-01

    Full Text Available BACKGROUND: Plasmodium vivax is the most prevalent human malaria parasite, causing serious public health problems in malaria-endemic countries. Until recently the Duffy-negative blood group phenotype was considered to confer resistance to vivax malaria for most African ethnicities. We and others have reported that P. vivax strains in African countries from Madagascar to Mauritania display capacity to cause clinical vivax malaria in Duffy-negative people. New insights must now explain Duffy-independent P. vivax invasion of human erythrocytes. METHODS/PRINCIPAL FINDINGS: Through recent whole genome sequencing we obtained ≥ 70× coverage of the P. vivax genome from five field-isolates, resulting in ≥ 93% of the Sal I reference sequenced at coverage greater than 20×. Combined with sequences from one additional Malagasy field isolate and from five monkey-adapted strains, we describe here identification of DNA sequence rearrangements in the P. vivax genome, including discovery of a duplication of the P. vivax Duffy binding protein (PvDBP gene. A survey of Malagasy patients infected with P. vivax showed that the PvDBP duplication was present in numerous locations in Madagascar and found in over 50% of infected patients evaluated. Extended geographic surveys showed that the PvDBP duplication was detected frequently in vivax patients living in East Africa and in some residents of non-African P. vivax-endemic countries. Additionally, the PvDBP duplication was observed in travelers seeking treatment of vivax malaria upon returning home. PvDBP duplication prevalence was highest in west-central Madagascar sites where the highest frequencies of P. vivax-infected, Duffy-negative people were reported. CONCLUSIONS/SIGNIFICANCE: The highly conserved nature of the sequence involved in the PvDBP duplication suggests that it has occurred in a recent evolutionary time frame. These data suggest that PvDBP, a merozoite surface protein involved in red cell adhesion

  10. Cryptic Xp duplication including the SHOX gene in a woman with 46,X, del(X)(q21.31) and premature ovarian failure.

    Science.gov (United States)

    Tachdjian, Gérard; Aboura, Azzedine; Portnoï, Marie-France; Pasquier, Maud; Bourcigaux, Nathalie; Simon, Tabassome; Rousseau, Ghislaine; Finkel, Lina; Benkhalifa, Moncef; Christin-Maitre, Sophie

    2008-01-01

    Premature ovarian failure (POF) is defined as amenorrhoea for >6 months, occurring before the age of 40, with an FSH serum level in the menopausal range. Although Xq deletions have been known for a long time to be associated with POF, the mechanisms involved in X deletions in order to explain ovarian failure remain unknown. In order to look for potentially cryptic chromosomal imbalance, we used high-resolution genomic analysis to characterize X chromosome deletions associated with POF. Three patients with POF presenting terminal Xq deletions detected by conventional cytogenetics were included in the study. Genome wide microarray comparative genomic hybridization (CGH) at a resolution of 1 Mb and fluorescence in situ hybridization (FISH) was performed. Microarray CGH and FISH studies characterized the three deletions as del(X)(q21.2), del(X)(q21.31) and del(X)(q22.33). Microarray CGH showed that the del(X)(q21.31) was also associated with a Xpter duplication including the SHOX gene. In these patients with POF, deletions or duplications of autosomes have been excluded. This study is the first one using microarray in patients with POF. It demonstrates that putative X chromosome deletions can be associated with other chromosomal imbalances such as duplications, and therefore illustrates the use of microarray CGH to screen chromosomal abnormalities in patients with POF.

  11. Chromosome I duplications in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    McKim, K.S.; Rose, A.M. (Univ. of British Columbia, Vancouver (Canada))

    1990-01-01

    We have isolated and characterized 76 duplications of chromosome I in the genome of Caenorhabditis elegans. The region studied is the 20 map unit left half of the chromosome. Sixty-two duplications were induced with gamma radiation and 14 arose spontaneously. The latter class was apparently the result of spontaneous breaks within the parental duplication. The majority of duplications behave as if they are free. Three duplications are attached to identifiable sequences from other chromosomes. The duplication breakpoints have been mapped by complementation analysis relative to genes on chromosome I. Nineteen duplication breakpoints and seven deficiency breakpoints divide the left half of the chromosome into 24 regions. We have studied the relationship between duplication size and segregational stability. While size is an important determinant of mitotic stability, it is not the only one. We observed clear exceptions to a size-stability correlation. In addition to size, duplication stability may be influenced by specific sequences or chromosome structure. The majority of the duplications were stable enough to be powerful tools for gene mapping. Therefore the duplications described here will be useful in the genetic characterization of chromosome I and the techniques we have developed can be adapted to other regions of the genome.

  12. Insights into the evolutionary history of tubercle bacilli as disclosed by genetic rearrangements within a PE_PGRS duplicated gene pair

    Directory of Open Access Journals (Sweden)

    Kurepina Natalia

    2006-12-01

    Full Text Available Abstract Background The highly homologous PE_PGRS (Proline-glutamic acid_polymorphic GC-rich repetitive sequence genes are members of the PE multigene family which is found only in mycobacteria. PE genes are particularly abundant within the genomes of pathogenic mycobacteria where they seem to have expanded as a result of gene duplication events. PE_PGRS genes are characterized by their high GC content and extensive repetitive sequences, making them prone to recombination events and genetic variability. Results Comparative sequence analysis of Mycobacterium tuberculosis genes PE_PGRS17 (Rv0978c and PE_PGRS18 (Rv0980c revealed a striking genetic variation associated with this typical tandem duplicate. In comparison to the M. tuberculosis reference strain H37Rv, the variation (named the 12/40 polymorphism consists of an in-frame 12-bp insertion invariably accompanied by a set of 40 single nucleotide polymorphisms (SNPs that occurs either in PE_PGRS17 or in both genes. Sequence analysis of the paralogous genes in a representative set of worldwide distributed tubercle bacilli isolates revealed data which supported previously proposed evolutionary scenarios for the M. tuberculosis complex (MTBC and confirmed the very ancient origin of "M. canettii" and other smooth tubercle bacilli. Strikingly, the identified polymorphism appears to be coincident with the emergence of the post-bottleneck successful clone from which the MTBC expanded. Furthermore, the findings provide direct and clear evidence for the natural occurrence of gene conversion in mycobacteria, which appears to be restricted to modern M. tuberculosis strains. Conclusion This study provides a new perspective to explore the molecular events that accompanied the evolution, clonal expansion, and recent diversification of tubercle bacilli.

  13. Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene

    OpenAIRE

    2013-01-01

    Objectives: Constitutive activation of the fms-like tyrosine kinase 3 (FLT3) receptor by internal tandem duplication (ITD) of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies investigated which FAB subtype is associated with higher percentage of FLT3/ITD, thus the reason for ...

  14. Allele frequency of a 24 bp duplication in exon 10 of the CHIT1 gene in the general Korean population and in Korean patients with Gaucher disease.

    Science.gov (United States)

    Woo, Kyu Ha; Lee, Beom Hee; Heo, Sun Hee; Kim, Jae-Min; Kim, Gu-Hwan; Kim, Yoo-Mi; Kim, Ja Hye; Choi, In-Hee; Yang, Song Hyun; Yoo, Han-Wook

    2014-05-01

    Plasma chitotriosidase activity is used for diagnosis and monitoring of Gaucher disease. However, homozygous duplication of a 24 bp region in exon 10 of the chitotriosidase gene (CHIT1) abolishes enzyme activity, limiting its use as a biomarker in Gaucher disease. This study investigates the allele frequency of the 24 bp duplication, in both the general Korean population and in patients with Gaucher disease. Fifteen Korean patients with Gaucher disease and 231 Korean normal individuals were enrolled. Genotyping was performed to identify the 24 bp duplication in exon 10 of CHIT1 using DNA extracted from peripheral leukocytes or dried blood spots. Two patients with Gaucher disease (13.3%) had normal plasma chitotriosidase activity, and carried a homozygous 24 bp duplication of exon 10 of the CHIT1 gene. Nine patients were heterozygote carriers (60.0%). Of the normal 231 Korean individuals, heterozygous duplication was detected in 109 individuals (47.2%) and homozygous duplication in 75 (32.5%). The allele frequency was 56.1% (95% confidence interval, 49.4-62.7%). The frequency of the 24 bp duplication was remarkably high in both Korean patients with Gaucher disease and in the normal population, limiting the efficacy of chitotriosidase as a biomarker in Gaucher disease in Korea. New biomarkers are required that consider the genetic characteristics of different populations.

  15. GENOME-WIDE INVESTIGATION OF HSF GENES IN SESAME REVEALS THEIR SEGMENTAL DUPLICATION EXPANSION AND THEIR ACTIVE ROLE IN DROUGHT STRESS RESPONSE

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    Komivi Dossa

    2016-10-01

    Full Text Available Sesame is a survivor crop cultivated for ages in arid areas under high temperatures and limited water conditions. Since its entire genome has been sequenced, revealing evolution and functional characterization of its abiotic stress genes became a hot topic. In this study, we performed a whole-genome identification and analysis of Hsf gene family in sesame. Thirty genes encoding Hsf domain were found and classified into 3 major classes A, B and C. The class A members were the most representative one and Hsf genes were distributed in 12 of the 16 linkage groups (except the LG 8, 9, 13 and 16. Evolutionary analysis revealed that, segmental duplication events which occurred around 67 MYA, were the primary force underlying Hsf genes expansion in sesame. Comparative analysis also suggested that sesame has retained most of its Hsf genes while its relatives viz. tomato and potato underwent extensive gene losses during evolution. Continuous purifying selection has played a key role in the maintenance of Hsf genes in sesame. Expression analysis of the Hsf genes in sesame revealed their putative involvement in multiple tissue-/developmental stages. Time-course expression profiling of Hsf genes in response to drought stress showed that 90% Hsfs are drought responsive. We infer that classes B-Hsfs might be the primary regulators of drought response in sesame by cooperating with some class A genes. This is the first insight into this gene family and the results provide some gene resources for future gene cloning and functional studies towards the improvement in stress tolerance of sesame.

  16. High frequency of additional gene mutations in acute myeloid leukemia with MLL partial tandem duplication: DNMT3A mutation is associated with poor prognosis.

    Science.gov (United States)

    Kao, Hsiao-Wen; Liang, D Cherng; Kuo, Ming-Chung; Wu, Jin-Hou; Dunn, Po; Wang, Po-Nan; Lin, Tung-Liang; Shih, Yu-Shu; Liang, Sung-Tzu; Lin, Tung-Huei; Lai, Chen-Yu; Lin, Chun-Hui; Shih, Lee-Yung

    2015-10-20

    The mutational profiles of acute myeloid leukemia (AML) with partial tandem duplication of mixed-lineage leukemia gene (MLL-PTD) have not been comprehensively studied. We studied 19 gene mutations for 98 patients with MLL-PTD AML to determine the mutation frequency and clinical correlations. MLL-PTD was screened by reverse-transcriptase PCR and confirmed by real-time quantitative PCR. The mutational analyses were performed with PCR-based assays followed by direct sequencing. Gene mutations of signaling pathways occurred in 63.3% of patients, with FLT3-ITD (44.9%) and FLT3-TKD (13.3%) being the most frequent. 66% of patients had gene mutations involving epigenetic regulation, and DNMT3A (32.7%), IDH2 (18.4%), TET2 (18.4%), and IDH1 (10.2%) mutations were most common. Genes of transcription pathways and tumor suppressors accounted for 23.5% and 10.2% of patients. RUNX1 mutation occurred in 23.5% of patients, while none had NPM1 or double CEBPA mutation. 90.8% of MLL-PTD AML patients had at least one additional gene mutation. Of 55 MLL-PTD AML patients who received standard chemotherapy, age older than 50 years and DNMT3A mutation were associated with inferior outcome. In conclusion, gene mutations involving DNA methylation and activated signaling pathway were common co-existed gene mutations. DNMT3A mutation was a poor prognostic factor in MLL-PTD AML.

  17. Genome-wide identification and comparative expression analysis reveal a rapid expansion and functional divergence of duplicated genes in the WRKY gene family of cabbage, Brassica oleracea var. capitata.

    Science.gov (United States)

    Yao, Qiu-Yang; Xia, En-Hua; Liu, Fei-Hu; Gao, Li-Zhi

    2015-02-15

    WRKY transcription factors (TFs), one of the ten largest TF families in higher plants, play important roles in regulating plant development and resistance. To date, little is known about the WRKY TF family in Brassica oleracea. Recently, the completed genome sequence of cabbage (B. oleracea var. capitata) allows us to systematically analyze WRKY genes in this species. A total of 148 WRKY genes were characterized and classified into seven subgroups that belong to three major groups. Phylogenetic and synteny analyses revealed that the repertoire of cabbage WRKY genes was derived from a common ancestor shared with Arabidopsis thaliana. The B. oleracea WRKY genes were found to be preferentially retained after the whole-genome triplication (WGT) event in its recent ancestor, suggesting that the WGT event had largely contributed to a rapid expansion of the WRKY gene family in B. oleracea. The analysis of RNA-Seq data from various tissues (i.e., roots, stems, leaves, buds, flowers and siliques) revealed that most of the identified WRKY genes were positively expressed in cabbage, and a large portion of them exhibited patterns of differential and tissue-specific expression, demonstrating that these gene members might play essential roles in plant developmental processes. Comparative analysis of the expression level among duplicated genes showed that gene expression divergence was evidently presented among cabbage WRKY paralogs, indicating functional divergence of these duplicated WRKY genes.

  18. Tandem duplication and copy number polymorphism of the SRY gene in patients with sex chromosome anomalies and males exposed to natural background radiation.

    Science.gov (United States)

    Premi, Sanjay; Srivastava, Jyoti; Chandy, Sebastian Padinjarel; Ahmad, Jamal; Ali, Sher

    2006-02-01

    Mutations in the SRY gene encompassing the HMG box have been well characterized in gonadal dysgenesis, male infertility and other types of sex chromosome related anomalies (SCRA). However, no information is available on copy number status of this gene under such abnormal conditions. Employing 'Taqman Probe Assay' specific to the SRY gene, we screened 16 DNA samples from patients with SCRA and 36 samples from males exposed to high levels of natural background radiation (HNBR). Patients with SCRA showed 2-16 copies of the SRY gene of which, one, Oxen (49, XYYYY) had eight copies with sequences different from one another. Of the 36 HNBR samples, 12 had one copy whereas 24 harboured 2-8 copies of the SRY gene. A HNBR male 33F had one normal and one mutated copy of this gene. Analysis of 25 DNA samples from blood and semen of normal males showed only one copy of this gene. Despite multiple copies in affected males, fluorescence in-situ hybridization (FISH) with SRY probe detected a single signal on the Y chromosome in HNBR males suggesting its possible localized tandem duplication. Copy number status of the other Y-linked loci is envisaged to augment DNA diagnostics facilitating genetic counselling to affected patients.

  19. A duplicated coxI gene is associated with cytoplasmic male sterility in an alloplasmic Brassica juncea line derived from somatic hybridization with Diplotaxis catholica

    Indian Academy of Sciences (India)

    Aruna Pathania; Rajesh Kumar; V. Dinesh Kumar; Ashutosh; K. K. Dwivedi; P. B. Kirti; P. Prakash; V. L. Chopra; S. R. Bhat

    2007-08-01

    A cytoplasmic male sterile (CMS) line of Brassica juncea was derived by repeated backcrossing of the somatic hybrid (Diplotaxis catholica + B. juncea) to B. juncea. The new CMS line is comparable to euplasmic lines for almost all characters, except for flowers which bear slender, needle-like anthers with aborted pollen. Detailed Southern analysis revealed two copies of coxI gene in the CMS line. One copy, coxI-1 is similar to the coxI gene of B. juncea, whereas the second copy, coxI-2 is present in a novel rearranged region. Northern analysis with eight mitochondrial gene probes showed altered transcript pattern only for the coxI gene. Two transcripts of 2.0 and 2.4 kb, respectively, were detected in the CMS line. The novel 2.4 kb transcript was present in floral bud tissue but absent in the leaf tissue. In plants where male sterility broke down under high temperature during the later part of the growing season, the 2.4 kb coxI transcript was absent, which suggested its association with the CMS. The two coxI genes from the CMS line showed two amino acid changes in the coding region. The novel coxI gene showed unique repeats in the 5′ region suggesting recombination of mitochondrial genomes of the two species. The possible role of the duplicated coxI gene in causing male sterility is discussed.

  20. Increased copy number for methylated maternal 15q duplications leads to changes in gene and protein expression in human cortical samples

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    Scoles Haley A

    2011-12-01

    Full Text Available Abstract Background Duplication of chromosome 15q11-q13 (dup15q accounts for approximately 3% of autism cases. Chromosome 15q11-q13 contains imprinted genes necessary for normal mammalian neurodevelopment controlled by a differentially methylated imprinting center (imprinting center of the Prader-Willi locus, PWS-IC. Maternal dup15q occurs as both interstitial duplications and isodicentric chromosome 15. Overexpression of the maternally expressed gene UBE3A is predicted to be the primary cause of the autistic features associated with dup15q. Previous analysis of two postmortem dup15q frontal cortical samples showed heterogeneity between the two cases, with one showing levels of the GABAA receptor genes, UBE3A and SNRPN in a manner not predicted by copy number or parental imprint. Methods Postmortem human brain tissue (Brodmann area 19, extrastriate visual cortex was obtained from 8 dup15q, 10 idiopathic autism and 21 typical control tissue samples. Quantitative PCR was used to confirm duplication status. Quantitative RT-PCR and Western blot analyses were performed to measure 15q11-q13 transcript and protein levels, respectively. Methylation-sensitive high-resolution melting-curve analysis was performed on brain genomic DNA to identify the maternal:paternal ratio of methylation at PWS-IC. Results Dup15q brain samples showed a higher level of PWS-IC methylation than control or autism samples, indicating that dup15q was maternal in origin. UBE3A transcript and protein levels were significantly higher than control and autism in dup15q, as expected, although levels were variable and lower than expected based on copy number in some samples. In contrast, this increase in copy number did not result in consistently increased GABRB3 transcript or protein levels for dup15q samples. Furthermore, SNRPN was expected to be unchanged in expression in dup15q because it is expressed from the single unmethylated paternal allele, yet SNRPN levels were significantly

  1. Peripheral myelin protein 22 gene duplication with atypical presentations: a new example of the wide spectrum of Charcot-Marie-Tooth 1A disease.

    Science.gov (United States)

    Mathis, Stéphane; Corcia, Philippe; Tazir, Meriem; Camu, William; Magdelaine, Corinne; Latour, Philippe; Biberon, Julien; Guennoc, Anne-Marie; Richard, Laurence; Magy, Laurent; Funalot, Benoît; Vallat, Jean-Michel

    2014-06-01

    Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are both autosomal-dominant disorders linked to peripheral myelin anomalies. CMT1A is associated with a Peripheral Myelin Protein 22 (PMP22) duplication, whereas HNPP is due to a PMP22 deletion on chromosome 17. In spite of this crucial difference, we report three observations of patients with the 1.4 megabase CMT1A duplication and atypical presentation (electrophysiological, clinical or pathological): a 10 year-old girl with tomaculous lesions on nerve biopsy; a 26 year-old woman with recurrent paresthesiae and block conduction on the electrophysiological study; a 46 year-old woman with transient recurrent nerve palsies mimicking HNPP. These observations highlight the wide spectrum of CMT1A and the overlap between CMT1A and HNPP (both linked to the PMP22 gene), and finally illustrate the complexity of the genotype-phenotype correlations in Charcot-Marie-Tooth diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene.

    Science.gov (United States)

    Santos-Cortez, Regie Lyn P; Hutchinson, Diane S; Ajami, Nadim J; Reyes-Quintos, Ma Rina T; Tantoco, Ma Leah C; Labra, Patrick John; Lagrana, Sheryl Mae; Pedro, Melquiadesa; Llanes, Erasmo Gonzalo D V; Gloria-Cruz, Teresa Luisa; Chan, Abner L; Cutiongco-de la Paz, Eva Maria; Belmont, John W; Chonmaitree, Tasnee; Abes, Generoso T; Petrosino, Joseph F; Leal, Suzanne M; Chiong, Charlotte M

    2016-11-01

    Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children. The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among indigenous Filipinos with poor health care access. Ear swabs were obtained from 16 indigenous Filipino individuals with chronic otitis media, of whom 11 carry the A2ML1 duplication variant. Ear swabs were submitted for 16S rRNA gene sequencing. Genotype-based differences in microbial richness, structure, and composition were identified, but were not statistically significant. Taxonomic analysis revealed that the relative abundance of the phyla Fusobacteria and Bacteroidetes, and genus Fusobacterium were nominally increased in carriers compared to non-carriers, but were non-significant after correction for multiple testing. We also detected rare bacteria including Oligella that was reported only once in the middle ear. These findings suggest that A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome. Knowledge of middle ear microbial profiles according to genetic background can be potentially useful for therapeutic and prophylactic interventions for otitis media and can guide public health interventions towards decreasing otitis media prevalence within the indigenous Filipino community.

  3. The evolution and appearance of C3 duplications in fish originate an exclusive teleost c3 gene form with anti-inflammatory activity.

    Directory of Open Access Journals (Sweden)

    Gabriel Forn-Cuní

    Full Text Available The complement system acts as a first line of defense and promotes organism homeostasis by modulating the fates of diverse physiological processes. Multiple copies of component genes have been previously identified in fish, suggesting a key role for this system in aquatic organisms. Herein, we confirm the presence of three different previously reported complement c3 genes (c3.1, c3.2, c3.3 and identify five additional c3 genes (c3.4, c3.5, c3.6, c3.7, c3.8 in the zebrafish genome. Additionally, we evaluate the mRNA expression levels of the different c3 genes during ontogeny and in different tissues under steady-state and inflammatory conditions. Furthermore, while reconciling the phylogenetic tree with the fish species tree, we uncovered an event of c3 duplication common to all teleost fishes that gave rise to an exclusive c3 paralog (c3.7 and c3.8. These paralogs showed a distinct ability to regulate neutrophil migration in response to injury compared with the other c3 genes and may play a role in maintaining the balance between inflammatory and homeostatic processes in zebrafish.

  4. Fractionation of Synteny in a Genomic Region Containing Tandemly Duplicated Genes Across Glycine max, Medicago truncatula and Arabidopsis thaliana

    Science.gov (United States)

    Extended comparison of gene sequences found on homeologous soybean BACs to Medicago truncatula and Arabidopsis thaliana genomic sequences demonstrated a network of synteny within conserved regions interrupted by gene addition and/or deletions. Consolidation of gene order among all three species prov...

  5. The roles of gene duplication, gene conversion and positive selection in rodent Esp and Mup pheromone gene families with comparison to the Abp family.

    Science.gov (United States)

    Karn, Robert C; Laukaitis, Christina M

    2012-01-01

    Three proteinaceous pheromone families, the androgen-binding proteins (ABPs), the exocrine-gland secreting peptides (ESPs) and the major urinary proteins (MUPs) are encoded by large gene families in the genomes of Mus musculus and Rattus norvegicus. We studied the evolutionary histories of the Mup and Esp genes and compared them with what is known about the Abp genes. Apparently gene conversion has played little if any role in the expansion of the mouse Class A and Class B Mup genes and pseudogenes, and the rat Mups. By contrast, we found evidence of extensive gene conversion in many Esp genes although not in all of them. Our studies of selection identified at least two amino acid sites in β-sheets as having evolved under positive selection in the mouse Class A and Class B MUPs and in rat MUPs. We show that selection may have acted on the ESPs by determining K(a)/K(s) for Exon 3 sequences with and without the converted sequence segment. While it appears that purifying selection acted on the ESP signal peptides, the secreted portions of the ESPs probably have undergone much more rapid evolution. When the inner gene converted fragment sequences were removed, eleven Esp paralogs were present in two or more pairs with K(a)/K(s) >1.0 and thus we propose that positive selection is detectable by this means in at least some mouse Esp paralogs. We compare and contrast the evolutionary histories of all three mouse pheromone gene families in light of their proposed functions in mouse communication.

  6. Molecular Characterization of Soybean Pterocarpan 2-Dimethylallyltransferase in Glyceollin Biosynthesis: Local Gene and Whole-Genome Duplications of Prenyltransferase Genes Led to the Structural Diversity of Soybean Prenylated Isoflavonoids.

    Science.gov (United States)

    Yoneyama, Keisuke; Akashi, Tomoyoshi; Aoki, Toshio

    2016-12-01

    Soybean (Glycine max) accumulates several prenylated isoflavonoid phytoalexins, collectively referred to as glyceollins. Glyceollins (I, II, III, IV and V) possess modified pterocarpan skeletons with C5 moieties from dimethylallyl diphosphate, and they are commonly produced from (6aS, 11aS)-3,9,6a-trihydroxypterocarpan [(-)-glycinol]. The metabolic fate of (-)-glycinol is determined by the enzymatic introduction of a dimethylallyl group into C-4 or C-2, which is reportedly catalyzed by regiospecific prenyltransferases (PTs). 4-Dimethylallyl (-)-glycinol and 2-dimethylallyl (-)-glycinol are precursors of glyceollin I and other glyceollins, respectively. Although multiple genes encoding (-)-glycinol biosynthetic enzymes have been identified, those involved in the later steps of glyceollin formation mostly remain unidentified, except for (-)-glycinol 4-dimethylallyltransferase (G4DT), which is involved in glyceollin I biosynthesis. In this study, we identified four genes that encode isoflavonoid PTs, including (-)-glycinol 2-dimethylallyltransferase (G2DT), using homology-based in silico screening and biochemical characterization in yeast expression systems. Transcript analyses illustrated that changes in G2DT gene expression were correlated with the induction of glyceollins II, III, IV and V in elicitor-treated soybean cells and leaves, suggesting its involvement in glyceollin biosynthesis. Moreover, the genomic signatures of these PT genes revealed that G4DT and G2DT are paralogs derived from whole-genome duplications of the soybean genome, whereas other PT genes [isoflavone dimethylallyltransferase 1 (IDT1) and IDT2] were derived via local gene duplication on soybean chromosome 11.

  7. Isolation of botulinolysin, a thiol-activated hemolysin, from serotype D Clostridium botulinum: A species-specific gene duplication in Clostridia.

    Science.gov (United States)

    Suzuki, Tomonori; Nagano, Thomas; Niwa, Koichi; Mutoh, Shingo; Uchino, Masataka; Tomizawa, Motohiro; Sagane, Yoshimasa; Watanabe, Toshihiro

    2016-12-01

    Botulinolysin (BLY) is a toxin produced by Clostridium botulinum that belongs to a group of thiol-activated hemolysins. In this study, a protein exhibiting hemolytic activity was purified from the culture supernatant of C. botulinum serotype D strain 4947. The purified protein displayed a single band by sodium dodecyl sulfate polyacrylamide gel electrophoresis with a molecular mass of 55kDa, and its N-terminal and internal amino acid sequences exhibited high similarity to a group of thiol-activated hemolysins produced by gram-positive bacteria. Thus, the purified protein was identified as the BLY. Using the nucleotide sequences of previously cloned genes for hemolysins, two types of genes encoding BLY-like proteins were cloned unexpectedly. Molecular modeling analysis indicated that the products of both genes displayed very similar structures, despite the low sequence similarity. In silico screening revealed a specific duplication of the hemolysin gene restricted to serotypes C and D of C. botulinum and their related species among thiol-activated hemolysin-producing bacteria. Our findings provide important insights into the genetic characteristics of pathogenic bacteria.

  8. Diagnosing Smith-Magenis syndrome and duplication 17p11.2 syndrome by RAI1 gene copy number variation using quantitative real-time PCR.

    Science.gov (United States)

    Truong, Hoa T; Solaymani-Kohal, Sara; Baker, Kevin R; Girirajan, Santhosh; Williams, Stephen R; Vlangos, Christopher N; Smith, Ann C M; Bunyan, David J; Roffey, Paul E; Blanchard, Christopher L; Elsea, Sarah H

    2008-03-01

    Smith-Magenis syndrome (SMS) and duplication 17p11.2 (dup17p11.2) syndrome are multiple congenital anomalies/mental retardation disorders resulting from either a deletion or duplication of the 17p11.2 region, respectively. The retinoic acid induced 1 (RAI1) gene is the causative gene for SMS and is included in the 17p11.2 region of dup17p11.2 syndrome. Currently SMS and dup17p11.2 syndrome are diagnosed using a combination of clinically recognized phenotypes and molecular cytogenetic analyses such as fluorescent in situ hybridization (FISH). However, these methods have proven to be highly expensive, time consuming, and dependent upon the low resolving capabilities of the assay. To address the need for improved diagnostic methods for SMS and dup17p11.2 syndrome, we designed a quantitative real-time PCR (Q-PCR) assay that measures RAI1 copy number using the comparative C(t) method, DeltaDeltaC(t). We tested our assay with samples blinded to their previous SMS or dup17p11.2 syndrome status. In all cases, we were able to determine RAI1 copy number status and render a correct diagnosis accordingly. We validated these results by both FISH and multiplex ligation-dependent probe amplification (MLPA). We conclude that Q-PCR is an accurate, reproducible, low-cost, and reliable assay that can be employed for routine use in SMS and dup17p11.2 diagnosis.

  9. Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence

    Directory of Open Access Journals (Sweden)

    Loncarevic Ivan F

    2004-12-01

    Full Text Available Abstract Background Defensins are important components of innate immunity to combat bacterial and viral infections, and can even elicit antitumor responses. Clusters of defensin (DEF genes are located in a 2 Mb range of the human chromosome 8p23.1. This DEF locus, however, represents one of the regions in the euchromatic part of the final human genome sequence which contains segmental duplications, and recalcitrant gaps indicating high structural dynamics. Results We find that inter- and intraindividual genetic variations within this locus prevent a correct automatic assembly of the human reference genome (NCBI Build 34 which currently even contains misassemblies. Manual clone-by-clone alignment and gene annotation as well as repeat and SNP/haplotype analyses result in an alternative alignment significantly improving the DEF locus representation. Our assembly better reflects the experimentally verified variability of DEF gene and DEF cluster copy numbers. It contains an additional DEF cluster which we propose to reside between two already known clusters. Furthermore, manual annotation revealed a novel DEF gene and several pseudogenes expanding the hitherto known DEF repertoire. Analyses of BAC and working draft sequences of the chimpanzee indicates that its DEF region is also complex as in humans and DEF genes and a cluster are multiplied. Comparative analysis of human and chimpanzee DEF genes identified differences affecting the protein structure. Whether this might contribute to differences in disease susceptibility between man and ape remains to be solved. For the determination of individual DEF gene repertoires we provide a molecular approach based on DEF haplotypes. Conclusions Complexity and variability seem to be essential genomic features of the human DEF locus at 8p23.1 and provides an ongoing challenge for the best possible representation in the human reference sequence. Dissection of paralogous sequence variations, duplicon SNPs ans

  10. Characterization of the interferon genes in homozygous rainbow trout reveals two novel genes, alternate splicing and differential regulation of duplicated genes.

    Science.gov (United States)

    Purcell, Maureen K; Laing, Kerry J; Woodson, James C; Thorgaard, Gary H; Hansen, John D

    2009-02-01

    The genes encoding the type I and type II interferons (IFNs) have previously been identified in rainbow trout and their proteins partially characterized. These previous studies reported a single type II IFN (rtIFN-gamma) and three rainbow trout type I IFN genes that are classified into either group I (rtIFN1, rtIFN2) or group II (rtIFN3). In this present study, we report the identification of a novel IFN-gamma gene (rtIFN-gamma2) and a novel type I group II IFN (rtIFN4) in homozygous rainbow trout and predict that additional IFN genes or pseudogenes exist in the rainbow trout genome. Additionally, we provide evidence that short and long forms of rtIFN1 are actively and differentially transcribed in homozygous trout, and likely arose due to alternate splicing of the first exon. Quantitative reverse transcriptase PCR (qRT-PCR) assays were developed to systematically profile all of the rainbow trout IFN transcripts, with high specificity at an individual gene level, in naïve fish and after stimulation with virus or viral-related molecules. Cloned PCR products were used to ensure the specificity of the qRT-PCR assays and as absolute standards to assess transcript abundance of each gene. All IFN genes were modulated in response to Infectious hematopoietic necrosis virus (IHNV), a DNA vaccine based on the IHNV glycoprotein, and poly I:C. The most inducible of the type I IFN genes, by all stimuli tested, were rtIFN3 and the short transcript form of rtIFN1. Gene expression of rtIFN-gamma1 and rtIFN-gamma2 was highly up-regulated by IHNV infection and DNA vaccination but rtIFN-gamma2 was induced to a greater magnitude. The specificity of the qRT-PCR assays reported here will be useful for future studies aimed at identifying which cells produce IFNs at early time points after infection.

  11. Characterization of the interferon genes in homozygous rainbow trout reveals two novel genes, alternate splicing and differential regulation of duplicated genes

    Science.gov (United States)

    Purcell, M.K.; Laing, K.J.; Woodson, J.C.; Thorgaard, G.H.; Hansen, J.D.

    2009-01-01

    The genes encoding the type I and type II interferons (IFNs) have previously been identified in rainbow trout and their proteins partially characterized. These previous studies reported a single type II IFN (rtIFN-??) and three rainbow trout type I IFN genes that are classified into either group I (rtIFN1, rtIFN2) or group II (rtIFN3). In this present study, we report the identification of a novel IFN-?? gene (rtIFN-??2) and a novel type I group II IFN (rtIFN4) in homozygous rainbow trout and predict that additional IFN genes or pseudogenes exist in the rainbow trout genome. Additionally, we provide evidence that short and long forms of rtIFN1 are actively and differentially transcribed in homozygous trout, and likely arose due to alternate splicing of the first exon. Quantitative reverse transcriptase PCR (qRT-PCR) assays were developed to systematically profile all of the rainbow trout IFN transcripts, with high specificity at an individual gene level, in na??ve fish and after stimulation with virus or viral-related molecules. Cloned PCR products were used to ensure the specificity of the qRT-PCR assays and as absolute standards to assess transcript abundance of each gene. All IFN genes were modulated in response to Infectious hematopoietic necrosis virus (IHNV), a DNA vaccine based on the IHNV glycoprotein, and poly I:C. The most inducible of the type I IFN genes, by all stimuli tested, were rtIFN3 and the short transcript form of rtIFN1. Gene expression of rtIFN-??1 and rtIFN-??2 was highly up-regulated by IHNV infection and DNA vaccination but rtIFN-??2 was induced to a greater magnitude. The specificity of the qRT-PCR assays reported here will be useful for future studies aimed at identifying which cells produce IFNs at early time points after infection. ?? 2008 Elsevier Ltd.

  12. MECP2 Duplication Syndrome

    DEFF Research Database (Denmark)

    Signorini, Cinzia; De Felice, Claudio; Leoncini, Silvia

    2016-01-01

    Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients...... and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy...... condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P ≤ 0.05). Such increases were...

  13. The combinatorics of tandem duplication trees.

    Science.gov (United States)

    Gascuel, Olivier; Hendy, Michael D; Jean-Marie, Alain; McLachlan, Robert

    2003-02-01

    We developed a recurrence relation that counts the number of tandem duplication trees (either rooted or unrooted) that are consistent with a set of n tandemly repeated sequences generated under the standard unequal recombination (or crossover) model of tandem duplications. The number of rooted duplication trees is exactly twice the number of unrooted trees, which means that on average only two positions for a root on a duplication tree are possible. Using the recurrence, we tabulated these numbers for small values of n. We also developed an asymptotic formula that for large n provides estimates for these numbers. These numbers give a priori probabilities for phylogenies of the repeated sequences to be duplication trees. This work extends earlier studies where exhaustive counts of the numbers for small n were obtained. One application showed the significance of finding that most maximum-parsimony trees constructed from repeat sequences from human immunoglobins and T-cell receptors were tandem duplication trees. Those findings provided strong support to the proposed mechanisms of tandem gene duplication. The recurrence relation also suggests efficient algorithms to recognize duplication trees and to generate random duplication trees for simulation. We present a linear-time recognition algorithm.

  14. Gene duplication and co-evolution of G1/S transcription factor specificity in fungi are essential for optimizing cell fitness.

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    Adi Hendler

    2017-05-01

    Full Text Available Transcriptional regulatory networks play a central role in optimizing cell survival. How DNA binding domains and cis-regulatory DNA binding sequences have co-evolved to allow the expansion of transcriptional networks and how this contributes to cellular fitness remains unclear. Here we experimentally explore how the complex G1/S transcriptional network evolved in the budding yeast Saccharomyces cerevisiae by examining different chimeric transcription factor (TF complexes. Over 200 G1/S genes are regulated by either one of the two TF complexes, SBF and MBF, which bind to specific DNA binding sequences, SCB and MCB, respectively. The difference in size and complexity of the G1/S transcriptional network across yeast species makes it well suited to investigate how TF paralogs (SBF and MBF and DNA binding sequences (SCB and MCB co-evolved after gene duplication to rewire and expand the network of G1/S target genes. Our data suggests that whilst SBF is the likely ancestral regulatory complex, the ancestral DNA binding element is more MCB-like. G1/S network expansion took place by both cis- and trans- co-evolutionary changes in closely related but distinct regulatory sequences. Replacement of the endogenous SBF DNA-binding domain (DBD with that from more distantly related fungi leads to a contraction of the SBF-regulated G1/S network in budding yeast, which also correlates with increased defects in cell growth, cell size, and proliferation.

  15. Genetic diversity of MHC class I loci in six non-model frogs is shaped by positive selection and gene duplication

    Science.gov (United States)

    Kiemnec-Tyburczy, K M; Richmond, J Q; Savage, A E; Lips, K R; Zamudio, K R

    2012-01-01

    Comparative studies of major histocompatibility complex (MHC) genes across vertebrate species can reveal the evolutionary processes that shape the structure and function of immune regulatory proteins. In this study, we characterized MHC class I sequences from six frog species representing three anuran families (Hylidae, Centrolenidae and Ranidae). Using cDNA from our focal species, we amplified a total of 79 unique sequences spanning exons 2–4 that encode the extracellular domains of the functional alpha chain protein. We compared intra- and interspecific nucleotide and amino-acid divergence, tested for recombination, and identified codon sites under selection by estimating the rate of non-synonymous to synonymous substitutions with multiple codon-based maximum likelihood methods. We determined that positive (diversifying) selection was acting on specific amino-acid sites located within the domains that bind pathogen-derived peptides. We also found significant signals of recombination across the physical distance of the genes. Finally, we determined that all the six species expressed two or three putative classical class I loci, in contrast to the single locus condition of Xenopus laevis. Our results suggest that MHC evolution in anurans is a dynamic process and that variation in numbers of loci and genetic diversity can exist among taxa. Thus, the accumulation of genetic data for more species will be useful in further characterizing the relative importance of processes such as selection, recombination and gene duplication in shaping MHC loci among amphibian lineages. PMID:22549517

  16. Self-compatibility in 'Cristobalina' sweet cherry is not associated with duplications or modified transcription levels of S-locus genes.

    Science.gov (United States)

    Wünsch, A; Tao, R; Hormaza, J I

    2010-07-01

    Sweet cherry shows S-RNase-based gametophytic self-incompatibility, which prevents self- and cross-fertilization between genetically related individuals. The specificity of the self-incompatible reaction is determined by two genes located in the S-locus. These encode a pistil-expressed ribonuclease (S-RNase) that inhibits self pollen tube growth, and a pollen-expressed F-box protein (SFB) that may be involved in the cytotoxicity of self-S-RNases. Initial genetic and pollination studies in a self-compatible sweet cherry cultivar, 'Cristobalina' (S (3) S (6)), showed that self-compatibility was caused by the loss of pollen function of both haplotypes (S (3) and S (6)). In this study, we further characterize self-compatibility in this genotype by molecular analysis of the S-locus. DNA blot analyses using S-RNase and SFB probes show no duplications of 'Cristobalina' S-locus genes or differences in the restriction patterns when compared with self-incompatible cultivars with the same S-genotype. Furthermore, reverse transcriptase-PCR of S-locus genes and quantitative reverse transcription-PCR of SFBs revealed no differences at the transcription level when compared with a self-incompatible genotype. The results of this study show that no differences at the S-locus can be correlated with self-compatibility, indicating the possible involvement of non-S-locus modifiers in self-incompatibility breakdown in this cultivar.

  17. De novo duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in a mentally retarded woman with short stature and premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2011-09-01

    Conclusion: A duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in female patients can be associated with clinical manifestations of mental retardation in addition to short stature and premature ovarian failure.

  18. Characterization of the duplicate L-SIGN and DC-SIGN genes in miiuy croaker and evolutionary analysis of L-SIGN in fishes.

    Science.gov (United States)

    Shu, Chang; Wang, Shanchen; Xu, Tianjun

    2015-05-01

    Dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN/CD209) and liver/lymph node-specific ICAM-grabbing non-integrin (L-SIGN/CD299) which are homologues of DC-SIGN are important members in C-type lectin receptors family as key molecules to recognize and eliminate pathogens in the innate immune system. DC-SIGN and L-SIGN have become hot topics in recent studies which both served as cell adhesion and phagocytic pathogen recognition receptors in mammals. However, there have been almost no studies of DC-SIGN and L-SIGN structure and characters in fish, only DC-SIGN in the zebrafish had been studied. In our study, we identified and characterized the full-length miiuy croaker (Miichthys miiuy) DC-SIGN (mmDC-SIGN) and L-SIGN (mmL-SIGN) genes. The sequence analysis results showed that mmDC-SIGN and mmL-SIGN have the same domains with other vertebrates except primates, and share some conserved motifs in CRD among all the vertebrates which play a crucial role in interacting with Ca(2+) and for recognizing mannose-containing motifs. Gene synteny of DC-SIGN and L-SIGN were analyzed for the first time and gene synteny of L-SIGN was conserved among the five fishes. Interestingly, one gene next to L-SIGN from gene synteny had high similarity with L-SIGN gene that was described as L-SIGN-like in fish species. While only one L-SIGN gene existed in other vertebrates, two L-SIGN in fish may be in consequence of the fish-specific genome duplication to adapt the specific environment. The evolutionary analysis showed that the ancestral lineages of L-SIGN gene in fishes experienced purifying selection and the current lineages of L-SIGN gene in fishes underwent positive selection, indicating that the ancestral lineages and current lineages of L-SIGN gene in fishes underwent different evolutionary patterns. Both mmDC-SIGN and mmL-SIGN were expressed in all tested tissues and ubiquitously up-regulated in infected liver, spleen and kidney at different sampling time points

  19. A large duplication in the gene for lysyl hydroxylase accounts for the type VI variant of Ehlers-Danlos syndrome in two siblings

    Energy Technology Data Exchange (ETDEWEB)

    Hautala, T.; Heikkinen, J.; Kivirikko, K.I.; Myllylae, R. (Univ. of Oulu (Finland))

    1993-02-01

    Ehlers-Danlos syndrome is a deterogeneous disorder characterized by joint hypermobility, skin hyperextensibility, fragility, and other sign of connective tissue involvement. In addition to these, the type VI variant of the disease has some special characteristics such as kyphoscoliosis and ocular abnormalities. The biochemical abnormality in most patients with this autosomal recessively inherited type IV variant is a deficiency in the activity of lysyl hydroxylase (EC 1.14,11.4), the enzyme catalyzing the formation of hydroxylysine in collagens and other proteins with collagen-like amino acid sequences. The type VI variant of Ehlers-Danlos syndrome was first identified in two sisters with a reduced amount of lysyl hydroxylase activity in their skin fibroblasts (S.R. Pinnell, S.M. Krane, J.E. Kenzora, and M.J. Glimcher (1972) N. Engl. J. Med. 286; 1013-1020). Our recent molecular cloning of lysyl hydroxylase has now made it possible to study the mutations leading to the deficiency in lysyl dydroxylase activity in these cells. Our data indicate that the mRNA for lysyl hydroxylase produced in the affected cells is about 4 kb in size, whereas it is 3.2 kb in the control cells. The sequencing of the cDNA for lysyl hydroxylase from the affected cells revealed an apparently homozygous duplication rearrangement of nucleotides 1176 to 1955, corresponding to amino acids 326 to 585 in the normal sequence. From Southern blotting data, the duplicated area in the gene equals about 6-9 kb and corresponds to seven exons. 35 refs., 4 figs.

  20. Characteristics and Prognosis of Adult Acute Myeloid Leukemia with Internal Tandem Duplication in the FLT3 Gene

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    Adhra Al-Mawali

    2013-11-01

    Full Text Available Objectives: Constitutive activation of the fms-like tyrosine kinase 3 (FLT3 receptor by internal tandem duplication (ITD of the juxtamembrane region has been described in patients with acute myeloid leukemia. FLT3/ITDs are present in about 20-30% of all acute myeloid leukemia cases. It has been shown that the mutation is correlated with worse prognosis. However, none of the previous studies investigated which FAB subtype is associated with higher percentage of FLT3/ITD, thus the reason for undertaking the current study.Methods: The prevalence and the potential prognostic impact of FLT3 mutations in 39 acute myeloid leukemia patients were analyzed by genomic polymerase chain reaction. Twelve samples with FLT3/ITDs and 27 acute myeloid leukemia samples without the mutations were compared with respect to clinical prognosis and FAB subtype. Results were correlated with cytogenetic data and the clinical response.Results: FLT3/ITD mutations were found in 31% of patients. FLT3/ITD was associated with similar clinical characteristics and was more prevalent in patients with normal karyotype (83%. Interestingly, half of the FLT3/ITD aberrations were found in patients with FAB M1 (50%, and fewer were found in patients with FAB M2 (8%, M4 (8%, and M5 (8%. Although less frequent in patients with cytogenetic aberrations, FLT3/ITDs were found in 17% of patients with t(15;17. Although the study was powered to 80%, patients with FLT3/ITD mutation did not show shorter complete remission duration or a higher relapse rate.Conclusion: The data confirm that FLT3/ITD mutations represent a common alteration in adult acute myeloid leukemia, mainly with normal karyotype (83% and de novo acute myeloid leukemia (75%, as compared to secondary acute myeloid leukemia (25% (p<0.001. It also showed that half of the M1-FAB subtype is FLT3/ITD positive. Therefore, FLT3/ITD is a therapeutic target, and thus inhibition of FLT3 tyrosine kinase activity may provide a new approach in

  1. Functional divergence of duplicated c-myc genes in a tetraploid fish, the common carp (Cyprinus carpio).

    Science.gov (United States)

    Futami, Kunihiko; Zhang, Huan; Okamoto, Nobuaki

    2005-12-19

    The proto-oncogene c-myc is thought to be one of the most important genes in controlling cell proliferation. In a tetraploid fish, two c-myc genes (CAM1 and CAM2) were previously isolated from the common carp, Cyprinus carpio, and were shown to have different expression patterns in adult tissues. Here we found that CAM1 and CAM2 proteins had distinct properties in terms of their transcription regulation system, formation of the transcription activator complex Myc/Max, and transcriptional activation of the target gene. These results showed that the two carp c-Myc proteins have overlapping but distinct functions, suggesting that CAM1 and CAM2 are evolving to acquire different functions after an earlier tetraploidization event.

  2. Role of the duplicated CCAAT box region in γ-globin gene regulation and hereditary persistence of fetal haemoglobin.

    NARCIS (Netherlands)

    A. Ronchi (Antonella); M. Berry (Meera); S. Raguz (Selina); A.M.A. Imam (Ali); N. Yannoutsos (Nikos); S. Ottolenghi (Sergio); F.G. Grosveld (Frank); N.O. Dillon (Niall)

    1996-01-01

    textabstractHereditary persistence of fetal haemoglobin (HPFH) is a clinically important condition in which a change in the developmental specificity of the gamma-globin genes results in varying levels of expression of fetal haemoglobin in the adult. The condition is benign and can significantly all

  3. Carboxylesterase 1 gene duplication and mRNA expression in adipose tissue are linked to obesity and metabolic function

    DEFF Research Database (Denmark)

    Friedrichsen, Martin; Poulsen, Pernille; Wojtaszewski, Jørgen

    2013-01-01

    involved in the control of mRNA expression. Here, we investigated mRNA expression level in adipose tissue and its association with measures of adiposity and metabolic function in a population of elderly twins. Furthermore, the heritability of mRNA expression level in adipose tissue and the effect of gene...

  4. The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16

    NARCIS (Netherlands)

    C.J. Ward (Christopher); B. Peral (Belén); J. Hughes (Jim); S. Thomas (Siep); V. Gamble (Vicki); A.B. MacCarthy (Angela); J. Sloane-Stanley (Jackie); P. Buckle (Peter); P. Kearney (Peter); D. Higgs (Douglas); C. Ratcliffe; P.C. Harris (Peter); J.H. Roelfsema (Jeroen); L. Spruit (Lia); J.J. Saris (Jasper); H.G. Dauwerse (Hans); D. Peters (Dorien); M.H. Breuning (Martijn); M.D. Nellist (Mark); P.T. Brook-Carter (Phillip); M.M. Maheshwar (Magitha); I. Cordeiro (Isabel); H. Santos (Heloisa); P. Cabral (Pedro); J. Sampson (Julian); L.A.J. Janssen (Bart); A.L.W. Hesseling-Janssen (Arjenne); A.M.W. van den Ouweland (Ans); H.J.F.M.M. Eussen (Bert); S. Verhoef; D. Lindhout (Dick); D.J.J. Halley (Dicky)

    1994-01-01

    textabstractAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently results in renal fallure due to progressive cyst development. The major locus, PKD1, maps to 16p13.3. We identified a chromosome translocation associated with ADPKD that disrupts a gene (PBP

  5. Disease association with two Helicobacter pylori duplicate outer membrane protein genes, homB and homA

    Directory of Open Access Journals (Sweden)

    Oleastro Monica

    2009-06-01

    Full Text Available Abstract Background homB encodes a Helicobacter pylori outer membrane protein. This gene was previously associated with peptic ulcer disease (PUD and was shown to induce activation of interleukin-8 secretion in vitro, as well as contributing to bacterial adherence. Its 90%-similar gene, homA, was previously correlated with gastritis. The present study aimed to evaluate the gastric disease association with homB and homA, as well as with the H. pylori virulence factors cagA, babA and vacA, in 415 H. pylori strains isolated from patients from East Asian and Western countries. The correlation among these genotypes was also evaluated. Results Both homB and homA genes were heterogeneously distributed worldwide, with a marked difference between East Asian and Western strains. In Western strains (n = 234, 124 PUD and 110 non-ulcer dyspepsia (NUD, homB, cagA and vacA s1 were all significantly associated with PUD (p = 0.025, p = 0.014, p = 0.039, respectively, and homA was closely correlated with NUD (p = 0.072. In East Asian strains (n = 138, 73 PUD and 65 NUD, homB was found more frequently than homA, and none of these genes was associated with the clinical outcome. Overall, homB was associated with the presence of cagA (p = 0.043 and vacA s1 (p homA was found more frequently in cagA-negative (p = 0.062 and vacA s2 (p Polymorphisms in homB and homA copy number were observed, with a clear geographical specificity, suggesting an involvement of these genes in host adaptation. A correlation between the homB two-copy genotype and PUD was also observed, emphasizing the role of homB in the virulence of the strain. Conclusion The global results suggest that homB and homA contribute to the determination of clinical outcome.

  6. Myxococcus xanthus DK1622 Coordinates Expressions of the Duplicate groEL and Single groES Genes for Synergistic Functions of GroELs and GroES

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    Yue-zhong Li

    2017-04-01

    Full Text Available Chaperonin GroEL (Cpn60 requires cofactor GroES (Cpn10 for protein refolding in bacteria that possess single groEL and groES genes in a bicistronic groESL operon. Among 4,861 completely-sequenced prokaryotic genomes, 884 possess duplicate groEL genes and 770 possess groEL genes with no neighboring groES. It is unclear whether stand-alone groEL requires groES in order to function and, if required, how duplicate groEL genes and unequal groES genes balance their expressions. In Myxococcus xanthus DK1622, we determined that, while duplicate groELs were alternatively deletable, the single groES that clusters with groEL1 was essential for cell survival. Either GroEL1 or GroEL2 required interactions with GroES for in vitro and in vivo functions. Deletion of groEL1 or groEL2 resulted in decreased expressions of both groEL and groES; and ectopic complementation of groEL recovered not only the groEL but also groES expressions. The addition of an extra groES gene upstream groEL2 to form a bicistronic operon had almost no influence on groES expression and the cell survival rate, whereas over-expression of groES using a self-replicating plasmid simultaneously increased the groEL expressions. The results indicated that M. xanthus DK1622 cells coordinate expressions of the duplicate groEL and single groES genes for synergistic functions of GroELs and GroES. We proposed a potential regulation mechanism for the expression coordination.

  7. A large new subset of TRIM genes highly diversified by duplication and positive selection in teleost fish

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    Herbomel Philippe

    2009-02-01

    Full Text Available Abstract Background In mammals, the members of the tripartite motif (TRIM protein family are involved in various cellular processes including innate immunity against viral infection. Viruses exert strong selective pressures on the defense system. Accordingly, antiviral TRIMs have diversified highly through gene expansion, positive selection and alternative splicing. Characterizing immune TRIMs in other vertebrates may enlighten their complex evolution. Results We describe here a large new subfamily of TRIMs in teleosts, called finTRIMs, identified in rainbow trout as virus-induced transcripts. FinTRIMs are formed of nearly identical RING/B-box regions and C-termini of variable length; the long variants include a B30.2 domain. The zebrafish genome harbors a striking diversity of finTRIMs, with 84 genes distributed in clusters on different chromosomes. A phylogenetic analysis revealed different subsets suggesting lineage-specific diversification events. Accordingly, the number of fintrim genes varies greatly among fish species. Conserved syntenies were observed only for the oldest fintrims. The closest mammalian relatives are trim16 and trim25, but they are not true orthologs. The B30.2 domain of zebrafish finTRIMs evolved under strong positive selection. The positions under positive selection are remarkably congruent in finTRIMs and in mammalian antiviral TRIM5α, concentrated within a viral recognition motif in mammals. The B30.2 domains most closely related to finTRIM are found among NOD-like receptors (NLR, indicating that the evolution of TRIMs and NLRs was intertwined by exon shuffling. Conclusion The diversity, evolution, and features of finTRIMs suggest an important role in fish innate immunity; this would make them the first TRIMs involved in immunity identified outside mammals.

  8. Carboxylesterase 1 gene duplication and mRNA expression in adipose tissue are linked to obesity and metabolic function

    DEFF Research Database (Denmark)

    Friedrichsen, Martin; Poulsen, Pernille; Wojtaszewski, Jørgen;

    2013-01-01

    involved in the control of mRNA expression. Here, we investigated mRNA expression level in adipose tissue and its association with measures of adiposity and metabolic function in a population of elderly twins. Furthermore, the heritability of mRNA expression level in adipose tissue and the effect of gene......CONTEXT AND AIMS: Carboxylesterase 1 (CES1) appears to play an important role in the control of the metabolism of triglycerides and cholesterol in adipocytes and other cell types including hepatocytes. Therefore, it is relevant to gain insights into the genetic versus non-genetic mechanisms...

  9. Startling mosaicism of the Y-chromosome and tandem duplication of the SRY and DAZ genes in patients with Turner Syndrome.

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    Sanjay Premi

    Full Text Available Presence of the human Y-chromosome in females with Turner Syndrome (TS enhances the risk of development of gonadoblastoma besides causing several other phenotypic abnormalities. In the present study, we have analyzed the Y chromosome in 15 clinically diagnosed Turner Syndrome (TS patients and detected high level of mosaicisms ranging from 45,XO:46,XY = 100:0% in 4; 45,XO:46,XY:46XX = 4:94:2 in 8; and 45,XO:46,XY:46XX = 50:30:20 cells in 3 TS patients, unlike previous reports showing 5-8% cells with Y- material. Also, no ring, marker or di-centric Y was observed in any of the cases. Of the two TS patients having intact Y chromosome in >85% cells, one was exceptionally tall. Both the patients were positive for SRY, DAZ, CDY1, DBY, UTY and AZFa, b and c specific STSs. Real Time PCR and FISH demonstrated tandem duplication/multiplication of the SRY and DAZ genes. At sequence level, the SRY was normal in 8 TS patients while the remaining 7 showed either absence of this gene or known and novel mutations within and outside of the HMG box. SNV/SFV analysis showed normal four copies of the DAZ genes in these 8 patients. All the TS patients showed aplastic uterus with no ovaries and no symptom of gonadoblastoma. Present study demonstrates new types of polymorphisms indicating that no two TS patients have identical genotype-phenotype. Thus, a comprehensive analysis of more number of samples is warranted to uncover consensus on the loci affected, to be able to use them as potential diagnostic markers.

  10. Duplication in DNA Sequences

    Science.gov (United States)

    Ito, Masami; Kari, Lila; Kincaid, Zachary; Seki, Shinnosuke

    The duplication and repeat-deletion operations are the basis of a formal language theoretic model of errors that can occur during DNA replication. During DNA replication, subsequences of a strand of DNA may be copied several times (resulting in duplications) or skipped (resulting in repeat-deletions). As formal language operations, iterated duplication and repeat-deletion of words and languages have been well studied in the literature. However, little is known about single-step duplications and repeat-deletions. In this paper, we investigate several properties of these operations, including closure properties of language families in the Chomsky hierarchy and equations involving these operations. We also make progress toward a characterization of regular languages that are generated by duplicating a regular language.

  11. Evolution after whole-genome duplication: a network perspective.

    Science.gov (United States)

    Zhu, Yun; Lin, Zhenguo; Nakhleh, Luay

    2013-11-06

    Gene duplication plays an important role in the evolution of genomes and interactomes. Elucidating how evolution after gene duplication interplays at the sequence and network level is of great interest. In this work, we analyze a data set of gene pairs that arose through whole-genome duplication (WGD) in yeast. All these pairs have the same duplication time, making them ideal for evolutionary investigation. We investigated the interplay between evolution after WGD at the sequence and network levels and correlated these two levels of divergence with gene expression and fitness data. We find that molecular interactions involving WGD genes evolve at rates that are three orders of magnitude slower than the rates of evolution of the corresponding sequences. Furthermore, we find that divergence of WGD pairs correlates strongly with gene expression and fitness data. Because of the role of gene duplication in determining redundancy in biological systems and particularly at the network level, we investigated the role of interaction networks in elucidating the evolutionary fate of duplicated genes. We find that gene neighborhoods in interaction networks provide a mechanism for inferring these fates, and we developed an algorithm for achieving this task. Further epistasis analysis of WGD pairs categorized by their inferred evolutionary fates demonstrated the utility of these techniques. Finally, we find that WGD pairs and other pairs of paralogous genes of small-scale duplication origin share similar properties, giving good support for generalizing our results from WGD pairs to evolution after gene duplication in general.

  12. The ERI-6/7 helicase acts at the first stage of an siRNA amplification pathway that targets recent gene duplications.

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    Sylvia E J Fischer

    2011-11-01

    Full Text Available Endogenous small interfering RNAs (siRNAs are a class of naturally occuring regulatory RNAs found in fungi, plants, and animals. Some endogenous siRNAs are required to silence transposons or function in chromosome segregation; however, the specific roles of most endogenous siRNAs are unclear. The helicase gene eri-6/7 was identified in the nematode Caenorhabditis elegans by the enhanced response to exogenous double-stranded RNAs (dsRNAs of the null mutant. eri-6/7 encodes a helicase homologous to small RNA factors Armitage in Drosophila, SDE3 in Arabidopsis, and Mov10 in humans. Here we show that eri-6/7 mutations cause the loss of 26-nucleotide (nt endogenous siRNAs derived from genes and pseudogenes in oocytes and embryos, as well as deficiencies in somatic 22-nucleotide secondary siRNAs corresponding to the same loci. About 80 genes are eri-6/7 targets that generate the embryonic endogenous siRNAs that silence the corresponding mRNAs. These 80 genes share extensive nucleotide sequence homology and are poorly conserved, suggesting a role for these endogenous siRNAs in silencing of and thereby directing the fate of recently acquired, duplicated genes. Unlike most endogenous siRNAs in C. elegans, eri-6/7-dependent siRNAs require Dicer. We identify that the eri-6/7-dependent siRNAs have a passenger strand that is ∼19 nt and is inset by ∼3-4 nts from both ends of the 26 nt guide siRNA, suggesting non-canonical Dicer processing. Mutations in the Argonaute ERGO-1, which associates with eri-6/7-dependent 26 nt siRNAs, cause passenger strand stabilization, indicating that ERGO-1 is required to separate the siRNA duplex, presumably through endonucleolytic cleavage of the passenger strand. Thus, like several other siRNA-associated Argonautes with a conserved RNaseH motif, ERGO-1 appears to be required for siRNA maturation.

  13. Duplication and concerted evolution of MiSp-encoding genes underlie the material properties of minor ampullate silks of cobweb weaving spiders.

    Science.gov (United States)

    Vienneau-Hathaway, Jannelle M; Brassfield, Elizabeth R; Lane, Amanda Kelly; Collin, Matthew A; Correa-Garhwal, Sandra M; Clarke, Thomas H; Schwager, Evelyn E; Garb, Jessica E; Hayashi, Cheryl Y; Ayoub, Nadia A

    2017-03-14

    Orb-web weaving spiders and their relatives use multiple types of task-specific silks. The majority of spider silk studies have focused on the ultra-tough dragline silk synthesized in major ampullate glands, but other silk types have impressive material properties. For instance, minor ampullate silks of orb-web weaving spiders are as tough as draglines, due to their higher extensibility despite lower strength. Differences in material properties between silk types result from differences in their component proteins, particularly members of the spidroin (spider fibroin) gene family. However, the extent to which variation in material properties within a single silk type can be explained by variation in spidroin sequences is unknown. Here, we compare the minor ampullate spidroins (MiSp) of orb-weavers and cobweb weavers. Orb-web weavers use minor ampullate silk to form the auxiliary spiral of the orb-web while cobweb weavers use it to wrap prey, suggesting that selection pressures on minor ampullate spidroins (MiSp) may differ between the two groups. We report complete or nearly complete MiSp sequences from five cobweb weaving spider species and measure material properties of minor ampullate silks in a subset of these species. We also compare MiSp sequences and silk properties of our cobweb weavers to published data for orb-web weavers. We demonstrate that all our cobweb weavers possess multiple MiSp loci and that one locus is more highly expressed in at least two species. We also find that the proportion of β-spiral-forming amino acid motifs in MiSp positively correlates with minor ampullate silk extensibility across orb-web and cobweb weavers. MiSp sequences vary dramatically within and among spider species, and have likely been subject to multiple rounds of gene duplication and concerted evolution, which have contributed to the diverse material properties of minor ampullate silks. Our sequences also provide templates for recombinant silk proteins with tailored

  14. Cloning and Characterization of a Differentially Expressed Phenylalanine Ammonialyase Gene (liPAL) After Genome Duplication from Tetraploid Isatis indigotica Fort.

    Institute of Scientific and Technical Information of China (English)

    Bei-Bei Lu; Zhen Du; Ru-Xian Ding; Lei Zhang; Xiao-Jing Yu; Cheng-Hong Liu; Wan-Sheng Chen

    2006-01-01

    Phenylpropanoid derivatives are a complex class of secondary metabolites that have many important roles in plants during normal growth and in responses to environmental stress. Phenylalanine ammonialyase(PAL) catalyzes the first step in the biosynthesis of phenylpropanoids. In the present study, we isolated a novel phenylalanine ammonialyase gene (designated as liPAL) from tetraploid Isatis indigotica Fort. by rapid amplification of cDNA ends (RACE), which was a cultivar from the diploid plant by genome duplication.The full-length cDNA of liPAL was 2 530-bp long with an open reading frame (ORF) of 2 178 bp encoding a polypeptide of 725 amino acid residues. Analysis of liPAL genomic DNA revealed that it was structurally similar to other plant PAL genes, with a single intron at a conserved position, and a long highly conserved second exon. Semi-quantitative RT-PCR revealed that the liPAL expression in roots and leaves from a tetraploid sample was higher than that in diploid progenitor, whereas expression of liPAL in stems was almost the same as each other. Furthermore, the highest expression of liPAL in tetraploid plant was found in roots, which was found in stems in diploid plants. Further expression analysis revealed that gibberellin (GA3), abscisic acid (ABA), methyl jasmonate (MeJA) and cold treatments could up-regulate the liPAL transcription in tetraploid plants. All our findings suggest that liPAL participates not only in the defense/stress responsive pathways, but also probably in the polyploidy evolution of I. indigotica.

  15. Directed evolution induces tributyrin hydrolysis in a virulence factor of Xylella fastidiosa using a duplicated gene as a template [v1; ref status: indexed, http://f1000r.es/48i

    Directory of Open Access Journals (Sweden)

    Hossein Gouran

    2014-09-01

    Full Text Available Duplication of genes is one of the preferred ways for natural selection to add advantageous functionality to the genome without having to reinvent the wheel with respect to catalytic efficiency and protein stability. The duplicated secretory virulence factors of Xylella fastidiosa (LesA, LesB and LesC, implicated in Pierce's disease of grape and citrus variegated chlorosis of citrus species, epitomizes the positive selection pressures exerted on advantageous genes in such pathogens. A deeper insight into the evolution of these lipases/esterases is essential to develop resistance mechanisms in transgenic plants. Directed evolution, an attempt to accelerate the evolutionary steps in the laboratory, is inherently simple when targeted for loss of function. A bigger challenge is to specify mutations that endow a new function, such as a lost functionality in a duplicated gene. Previously, we have proposed a method for enumerating candidates for mutations intended to transfer the functionality of one protein into another related protein based on the spatial and electrostatic properties of the active site residues (DECAAF. In the current work, we present in vivo validation of DECAAF by inducing tributyrin hydrolysis in LesB based on the active site similarity to LesA. The structures of these proteins have been modeled using RaptorX based on the closely related LipA protein from Xanthomonas oryzae. These mutations replicate the spatial and electrostatic conformation of LesA in the modeled structure of the mutant LesB as well, providing in silico validation before proceeding to the laborious in vivo work. Such focused mutations allows one to dissect the relevance of the duplicated genes in finer detail as compared to gene knockouts, since they do not interfere with other moonlighting functions, protein expression levels or protein-protein interaction.

  16. Middle ear microbiome differences in indigenous Filipinos with chronic otitis media due to a duplication in the A2ML1 gene

    National Research Council Canada - National Science Library

    Santos-Cortez, Regie Lyn P; Hutchinson, Diane S; Ajami, Nadim J; Reyes-Quintos, Ma. Rina T; Tantoco, Ma. Leah C; Labra, Patrick John; Lagrana, Sheryl Mae; Pedro, Melquiadesa; Llanes, Erasmo Gonzalo d. V; Gloria-Cruz, Teresa Luisa; Chan, Abner L; Cutiongco-de la Paz, Eva Maria; Belmont, John W; Chonmaitree, Tasnee; Abes, Generoso T; Petrosino, Joseph F; Leal, Suzanne M; Chiong, Charlotte M

    2016-01-01

    .... The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among...

  17. Analysis of recent segmental duplications in the bovine genome

    Directory of Open Access Journals (Sweden)

    Li Congjun

    2009-12-01

    Full Text Available Abstract Background Duplicated sequences are an important source of gene innovation and structural variation within mammalian genomes. We performed the first systematic and genome-wide analysis of segmental duplications in the modern domesticated cattle (Bos taurus. Using two distinct computational analyses, we estimated that 3.1% (94.4 Mb of the bovine genome consists of recently duplicated sequences (≥ 1 kb in length, ≥ 90% sequence identity. Similar to other mammalian draft assemblies, almost half (47% of 94.4 Mb of these sequences have not been assigned to cattle chromosomes. Results In this study, we provide the first experimental validation large duplications and briefly compared their distribution on two independent bovine genome assemblies using fluorescent in situ hybridization (FISH. Our analyses suggest that the (75-90% of segmental duplications are organized into local tandem duplication clusters. Along with rodents and carnivores, these results now confidently establish tandem duplications as the most likely mammalian archetypical organization, in contrast to humans and great ape species which show a preponderance of interspersed duplications. A cross-species survey of duplicated genes and gene families indicated that duplication, positive selection and gene conversion have shaped primates, rodents, carnivores and ruminants to different degrees for their speciation and adaptation. We identified that bovine segmental duplications corresponding to genes are significantly enriched for specific biological functions such as immunity, digestion, lactation and reproduction. Conclusion Our results suggest that in most mammalian lineages segmental duplications are organized in a tandem configuration. Segmental duplications remain problematic for genome and assembly and we highlight genic regions that require higher quality sequence characterization. This study provides insights into mammalian genome evolution and generates a valuable

  18. FhuD1, a Ferric Hydroxamate-binding Lipoprotein in Staphylococcus aureus - A case of gene duplication and lateral transfer

    Energy Technology Data Exchange (ETDEWEB)

    Sebulsky, M. Tom; Speziali, Craig D.; Shilton, Brian H.; Edgell, David R. (UWO)

    2010-11-16

    Staphylococcus aureus can utilize ferric hydroxamates as a source of iron under iron-restricted growth conditions. Proteins involved in this transport process are: FhuCBG, which encodes a traffic ATPase; FhuD2, a post-translationally modified lipoprotein that acts as a high affinity receptor at the cytoplasmic membrane for the efficient capture of ferric hydroxamates; and FhuD1, a protein with similarity to FhuD2. Gene duplication likely gave rise to fhuD1 and fhuD2. While the genomic locations of fhuCBG and fhuD2 in S. aureus strains are conserved, both the presence and the location of fhuD1 are variable. The apparent redundancy of FhuD1 led us to examine the role of this protein. We demonstrate that FhuD1 is expressed only under conditions of iron limitation through the regulatory activity of Fur. FhuD1 fractions with the cell membrane and binds hydroxamate siderophores but with lower affinity than FhuD2. Using small angle x-ray scattering, the solution structure of FhuD1 resembles that of FhuD2, and only a small conformational change is associated with ferrichrome binding. FhuD1, therefore, appears to be a receptor for ferric hydroxamates, like FhuD2. Our data to date suggest, however, that FhuD1 is redundant to FhuD2 and plays a minor role in hydroxamate transport. However, given the very real possibility that we have not yet identified the proper conditions where FhuD1 does provide an advantage over FhuD2, we anticipate that FhuD1 serves an enhanced role in the transport of untested hydroxamate siderophores and that it may play a prominent role during the growth of S. aureus in its natural environments.

  19. Distal Xq duplication and functional Xq disomy

    Directory of Open Access Journals (Sweden)

    Schluth-Bolard Caroline

    2009-02-01

    Full Text Available Abstract Distal Xq duplications refer to chromosomal disorders resulting from involvement of the long arm of the X chromosome (Xq. Clinical manifestations widely vary depending on the gender of the patient and on the gene content of the duplicated segment. Prevalence of Xq duplications remains unknown. About 40 cases of Xq28 functional disomy due to cytogenetically visible rearrangements, and about 50 cases of cryptic duplications encompassing the MECP2 gene have been reported. The most frequently reported distal duplications involve the Xq28 segment and yield a recognisable phenotype including distinctive facial features (premature closure of the fontanels or ridged metopic suture, broad face with full cheeks, epicanthal folds, large ears, small and open mouth, ear anomalies, pointed nose, abnormal palate and facial hypotonia, major axial hypotonia, severe developmental delay, severe feeding difficulties, abnormal genitalia and proneness to infections. Xq duplications may be caused either by an intrachromosomal duplication or an unbalanced X/Y or X/autosome translocation. In XY males, structural X disomy always results in functional disomy. In females, failure of X chromosome dosage compensation could result from a variety of mechanisms, including an unfavourable pattern of inactivation, a breakpoint separating an X segment from the X-inactivation centre in cis, or a small ring chromosome. The MECP2 gene in Xq28 is the most important dosage-sensitive gene responsible for the abnormal phenotype in duplications of distal Xq. Diagnosis is based on clinical features and is confirmed by CGH array techniques. Differential diagnoses include Prader-Willi syndrome and Alpha thalassaemia-mental retardation, X linked (ATR-X. The recurrence risk is significant if a structural rearrangement is present in one of the parent, the most frequent situation being that of an intrachromosomal duplication inherited from the mother. Prenatal diagnosis is performed by

  20. Clinical characterization and identification of duplication breakpoints in a Japanese family with Xq28 duplication syndrome including MECP2.

    Science.gov (United States)

    Fukushi, Daisuke; Yamada, Kenichiro; Nomura, Noriko; Naiki, Misako; Kimura, Reiko; Yamada, Yasukazu; Kumagai, Toshiyuki; Yamaguchi, Kumiko; Miyake, Yoshishige; Wakamatsu, Nobuaki

    2014-04-01

    Xq28 duplication syndrome including MECP2 is a neurodevelopmental disorder characterized by axial hypotonia at infancy, severe intellectual disability, developmental delay, mild characteristic facial appearance, epilepsy, regression, and recurrent infections in males. We identified a Japanese family of Xq28 duplications, in which the patients presented with cerebellar ataxia, severe constipation, and small feet, in addition to the common clinical features. The 488-kb duplication spanned from L1CAM to EMD and contained 17 genes, two pseudo genes, and three microRNA-coding genes. FISH and nucleotide sequence analyses demonstrated that the duplication was tandem and in a forward orientation, and the duplication breakpoints were located in AluSc at the EMD side, with a 32-bp deletion, and LTR50 at the L1CAM side, with "tc" and "gc" microhomologies at the duplication breakpoints, respectively. The duplicated segment was completely segregated from the grandmother to the patients. These results suggest that the duplication was generated by fork-stalling and template-switching at the AluSc and LTR50 sites. This is the first report to determine the size and nucleotide sequences of the duplicated segments at Xq28 of three generations of a family and provides the genotype-phenotype correlation of the patients harboring the specific duplicated segment.

  1. Evolution of the Neuropeptide Y Receptor Family: Gene and Chromosome Duplications Deduced from the Cloning and Mapping of the Five Receptor Subtype Genes in Pig

    OpenAIRE

    Wraith, Amanda; Törnsten, Anna; Chardon, Patrick; Harbitz, Ingrid; Chowdhary, Bhanu P.; Andersson, Leif; Lundin, Lars-Gustav; Larhammar, Dan

    2000-01-01

    Neuropeptide Y (NPY) receptors mediate a variety of physiological responses including feeding and vasoconstriction. To investigate the evolutionary events that have generated this receptor family, we have sequenced and determined the chromosomal localizations of all five presently known mammalian NPY receptor subtype genes in the domestic pig, Sus scrofa (SSC). The orthologs of the Y1 and Y2 subtypes display high amino acid sequence identities between pig, human, and mouse (92%–94%), whereas ...

  2. A conserved segmental duplication within ELA.

    Science.gov (United States)

    Brinkmeyer-Langford, C L; Murphy, W J; Childers, C P; Skow, L C

    2010-12-01

    The assembled genomic sequence of the horse major histocompatibility complex (MHC) (equine lymphocyte antigen, ELA) is very similar to the homologous human HLA, with the notable exception of a large segmental duplication at the boundary of ELA class I and class III that is absent in HLA. The segmental duplication consists of a ∼ 710 kb region of at least 11 repeated blocks: 10 blocks each contain an MHC class I-like sequence and the helicase domain portion of a BAT1-like sequence, and the remaining unit contains the full-length BAT1 gene. Similar genomic features were found in other Perissodactyls, indicating an ancient origin, which is consistent with phylogenetic analyses. Reverse-transcriptase PCR (RT-PCR) of mRNA from peripheral white blood cells of healthy and chronically or acutely infected horses detected transcription from predicted open reading frames in several of the duplicated blocks. This duplication is not present in the sequenced MHCs of most other mammals, although a similar feature at the same relative position is present in the feline MHC (FLA). Striking sequence conservation throughout Perissodactyl evolution is consistent with a functional role for at least some of the genes included within this segmental duplication.

  3. A Duplicate Construction Experiment.

    Science.gov (United States)

    Bridgeman, Brent

    This experiment was designed to assess the ability of item writers to construct truly parallel tests based on a "duplicate-construction experiment" in which Cronbach argues that if the universe description and sampling are ideally refined, the two independently constructed tests will be entirely equivalent, and that within the limits of item…

  4. Near Duplicate Document Detection Survey

    Directory of Open Access Journals (Sweden)

    Bassma S. Alsulami

    2012-04-01

    Full Text Available Search engines are the major breakthrough on the web for retrieving the information. But List of retrieved documents contains a high percentage of duplicated and near document result. So there is the need to improve the performance of search results. Some of current search engine use data filtering algorithm which can eliminate duplicate and near duplicate documents to save the users’ time and effort. The identification of similar or near-duplicate pairs in a large collection is a significant problem with wide-spread applications. In this paper survey present an up-to-date review of the existing literature in duplicate and near duplicate detection in Web

  5. BcMF26a and BcMF26b Are Duplicated Polygalacturonase Genes with Divergent Expression Patterns and Functions in Pollen Development and Pollen Tube Formation in Brassica campestris.

    Directory of Open Access Journals (Sweden)

    Meiling Lyu

    Full Text Available Polygalacturonase (PG is one of the cell wall hydrolytic enzymes involving in pectin degradation. A comparison of two highly conserved duplicated PG genes, namely, Brassica campestris Male Fertility 26a (BcMF26a and BcMF26b, revealed the different features of their expression patterns and functions. We found that these two genes were orthologous genes of At4g33440, and they originated from a chromosomal segmental duplication. Although structurally similar, their regulatory and intron sequences largely diverged. QRT-PCR analysis showed that the expression level of BcMF26b was higher than that of BcMF26a in almost all the tested organs and tissues in Brassica campestris. Promoter activity analysis showed that, at reproductive development stages, BcMF26b promoter was active in tapetum, pollen grains, and pistils, whereas BcMF26a promoter was only active in pistils. In the subcellular localization experiment, BcMF26a and BcMF26b proteins could be localized to the cell wall. When the two genes were co-inhibited, pollen intine was formed abnormally and pollen tubes could not grow or stretch. Moreover, the knockout mutants of At4g33440 delayed the growth of pollen tubes. Therefore, BcMF26a/b can participate in the construction of pollen wall by modulating intine information and BcMF26b may play a major role in co-inhibiting transformed plants.

  6. Metabolic Adaptation after Whole Genome Duplication

    NARCIS (Netherlands)

    Hoek, M.J.A. van; Hogeweg, P.

    2009-01-01

    Whole genome duplications (WGDs) have been hypothesized to be responsible for major transitions in evolution. However, the effects of WGD and subsequent gene loss on cellular behavior and metabolism are still poorly understood. Here we develop a genome scale evolutionary model to study the dynamics

  7. MR Imaging Findings in Xp21.2 Duplication Syndrome

    Science.gov (United States)

    Whitehead, Matthew T; Helman, Guy; Gropman, Andrea L

    2016-01-01

    Xp21.2 duplication syndrome is a rare genetic disorder of undetermined prevalence and clinical relevance. As the use of chromosomal microarray has become first line for the work-up of childhood developmental delay, more gene deletions and duplications have been recognized. To the best of our knowledge, the imaging findings of Xp21.2 duplication syndrome have not been reported. We report a case of a 33 month-old male referred for developmental delay that was found to have an Xp21.2 duplication containing IL1RAPL1 and multiple midline brain malformations.

  8. Identification of deletions and duplications in the Duchenne muscular dystrophy gene and female carrier status in western India using combined methods of multiplex polymerase chain reaction and multiplex ligation-dependent probe amplification

    Directory of Open Access Journals (Sweden)

    Rashna S Dastur

    2011-01-01

    Full Text Available Background: The technique of multiplex ligation-dependent probe amplification (MLPA assay is an advanced technique to identify deletions and duplications of all the 79 exons of DMD gene in patients with Duchenne/Becker muscular dystrophy (DMD/BMD and female carriers. Aim: To use MLPA assay to detect deletions which remained unidentified on multiplex polymerase chain reaction (mPCR analysis, scanning 32 exons of the "hot spot" region. Besides knowing the deletions and/or duplications, MLPA was also used to determine the carrier status of the females at risk. Materials and Methods: Twenty male patients showing no deletions on mPCR and 10 suspected carrier females were studied by MLPA assay using P-034 and P-035, probe sets (MRC Holland covering all the 79 exons followed by capillary electrophoresis on sequencing system. Results: On MLPA analysis, nine patients showed deletions of exons other than 32 exons screened by mPCR represented by absence of peak. Value of peak areas were double or more in four patients indicating duplications of exons. Carrier status was confirmed in 50% of females at risk. Conclusion: Combining the two techniques, mPCR followed by MLPA assay, has enabled more accurate detection and extent of deletions and duplications which otherwise would have remained unidentified, thereby increasing the mutation pick up rate. These findings have also allowed prediction of expected phenotype. Determining carrier status has a considerable significance in estimating the risk in future pregnancies and prenatal testing options to limit the birth of affected individuals.

  9. Gastric, pancreatic, and ureteric duplication

    Directory of Open Access Journals (Sweden)

    Chattopadhyay Anindya

    2010-01-01

    Full Text Available We report a case of an 8-month-old, asymptomatic child who was incidentally detected to have two cystic structures in the abdomen. Surgical exploration revealed a gastric and pancreatic duplication cyst along with a blind-ending duplication of the right ureter. Excision of the duplications was relatively straightforward, and the child made an uneventful recovery. This constellation of duplications has not been reported before.

  10. MECP2 duplication: possible cause of severe phenotype in females.

    Science.gov (United States)

    Scott Schwoerer, Jessica; Laffin, Jennifer; Haun, Joanne; Raca, Gordana; Friez, Michael J; Giampietro, Philip F

    2014-04-01

    MECP2 duplication syndrome, originally described in 2005, is an X-linked neurodevelopmental disorder comprising infantile hypotonia, severe to profound intellectual disability, autism or autistic-like features, spasticity, along with a variety of additional features that are not always clinically apparent. The syndrome is due to a duplication (or triplication) of the gene methyl CpG binding protein 2 (MECP2). To date, the disorder has been described almost exclusively in males. Female carriers of the duplication are thought to have no or mild phenotypic features. Recently, a phenotype for females began emerging. We describe a family with ∼290 kb duplication of Xq28 region that includes the MECP2 gene where the proposita and affected family members are female. Twin sisters, presumed identical, presented early with developmental delay, and seizures. Evaluation of the proposita at 25 years of age included microarray comparative genomic hybridization (aCGH) which revealed the MECP2 gene duplication. The same duplication was found in the proposita's sister, who is more severely affected, and the proband's mother who has mild intellectual disability and depression. X-chromosome inactivation studies showed significant skewing in the mother, but was uninformative in the twin sisters. We propose that the MECP2 duplication caused for the phenotype of the proband and her sister. These findings support evidence for varied severity in some females with MECP2 duplications.

  11. An Introduction to Duplicate Detection

    CERN Document Server

    Nauman, Felix

    2010-01-01

    With the ever increasing volume of data, data quality problems abound. Multiple, yet different representations of the same real-world objects in data, duplicates, are one of the most intriguing data quality problems. The effects of such duplicates are detrimental; for instance, bank customers can obtain duplicate identities, inventory levels are monitored incorrectly, catalogs are mailed multiple times to the same household, etc. Automatically detecting duplicates is difficult: First, duplicate representations are usually not identical but slightly differ in their values. Second, in principle

  12. The Sequence and Analysis of Duplication Rich Human Chromosome 16

    Science.gov (United States)

    Martin, Joel; Han, Cliff; Gordon, Laurie A.; Terry, Astrid; Prabhakar, Shyam; She, Xinwei; Xie, Gary; Hellsten, Uffe; Man Chan, Yee; Altherr, Michael; Couronne, Olivier; Aerts, Andrea; Bajorek, Eva; Black, Stacey; Blumer, Heather; Branscomb, Elbert; Brown, Nancy C.; Bruno, William J.; Buckingham, Judith M.; Callen, David F.; Campbell, Connie S.; Campbell, Mary L.; Campbell, Evelyn W.; Caoile, Chenier; Challacombe, Jean F.; Chasteen, Leslie A.; Chertkov, Olga; Chi, Han C.; Christensen, Mari; Clark, Lynn M.; Cohn, Judith D.; Denys, Mirian; Detter, John C.; Dickson, Mark; Dimitrijevic-Bussod, Mira; Escobar, Julio; Fawcett, Joseph J.; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstein, David; Goodwin, Lynne A.; Grady, Deborah L.; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Hildebrand, Carl E.; Huang, Wayne; Israni, Sanjay; Jett, Jamie; Jewett, Phillip E.; Kadner, Kristen; Kimball, Heather; Kobayashi, Arthur; Krawczyk, Marie-Claude; Leyba, Tina; Longmire, Jonathan L.; Lopez, Frederick; Lou, Yunian; Lowry, Steve; Ludeman, Thom; Mark, Graham A.; Mcmurray, Kimberly L.; Meincke, Linda J.; Morgan, Jenna; Moyzis, Robert K.; Mundt, Mark O.; Munk, A. Christine; Nandkeshwar, Richard D.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Parson-Quintana, Beverly; Ramirez, Lucia; Rash, Sam; Retterer, James; Ricke, Darryl O.; Robinson, Donna L.; Rodriguez, Alex; Salamov, Asaf; Saunders, Elizabeth H.; Scott, Duncan; Shough, Timothy; Stallings, Raymond L.; Stalvey, Malinda; Sutherland, Robert D.; Tapia, Roxanne; Tesmer, Judith G.; Thayer, Nina; Thompson, Linda S.; Tice, Hope; Torney, David C.; Tran-Gyamfi, Mary; Tsai, Ming; Ulanovsky, Levy E.; Ustaszewska, Anna; Vo, Nu; White, P. Scott; Williams, Albert L.; Wills, Patricia L.; Wu, Jung-Rung; Wu, Kevin; Yang, Joan; DeJong, Pieter; Bruce, David; Doggett, Norman; Deaven, Larry; Schmutz, Jeremy; Grimwood, Jane; Richardson, Paul; et al.

    2004-01-01

    We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility.

  13. The sequence and analysis of duplication rich human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Joel; Han, Cliff; Gordon, Laurie A.; Terry, Astrid; Prabhakar, Shyam; She, Xinwei; Xie, Gary; Hellsten, Uffe; Man Chan, Yee; Altherr, Michael; Couronne, Olivier; Aerts, Andrea; Bajorek, Eva; Black, Stacey; Blumer, Heather; Branscomb, Elbert; Brown, Nancy C.; Bruno, William J.; Buckingham, Judith M.; Callen, David F.; Campbell, Connie S.; Campbell, Mary L.; Campbell, Evelyn W.; Caoile, Chenier; Challacombe, Jean F.; Chasteen, Leslie A.; Chertkov, Olga; Chi, Han C.; Christensen, Mari; Clark, Lynn M.; Cohn, Judith D.; Denys, Mirian; Detter, John C.; Dickson, Mark; Dimitrijevic-Bussod, Mira; Escobar, Julio; Fawcett, Joseph J.; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstein, David; Goodwin, Lynne A.; Grady, Deborah L.; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Hildebrand, Carl E.; Huang, Wayne; Israni, Sanjay; Jett, Jamie; Jewett, Phillip E.; Kadner, Kristen; Kimball, Heather; Kobayashi, Arthur; Krawczyk, Marie-Claude; Leyba, Tina; Longmire, Jonathan L.; Lopez, Frederick; Lou, Yunian; Lowry, Steve; Ludeman, Thom; Mark, Graham A.; Mcmurray, Kimberly L.; Meincke, Linda J.; Morgan, Jenna; Moyzis, Robert K.; Mundt, Mark O.; Munk, A. Christine; Nandkeshwar, Richard D.; Pitluck, Sam; Pollard, Martin; Predki, Paul; Parson-Quintana, Beverly; Ramirez, Lucia; Rash, Sam; Retterer, James; Ricke, Darryl O.; Robinson, Donna L.; Rodriguez, Alex; Salamov, Asaf; Saunders, Elizabeth H.; Scott, Duncan; Shough, Timothy; Stallings, Raymond L.; Stalvey, Malinda; Sutherland, Robert D.; Tapia, Roxanne; Tesmer, Judith G.; Thayer, Nina; Thompson, Linda S.; Tice, Hope; Torney, David C.; Tran-Gyamfi, Mary; Tsai, Ming; Ulanovsky, Levy E.; Ustaszewska, Anna; Vo, Nu; White, P. Scott; Williams, Albert L.; Wills, Patricia L.; Wu, Jung-Rung; Wu, Kevin; Yang, Joan; DeJong, Pieter; Bruce, David; Doggett, Norman; Deaven, Larry; Schmutz, Jeremy; Grimwood, Jane; Richardson, Paul; et al.

    2004-08-01

    We report here the 78,884,754 base pairs of finished human chromosome 16 sequence, representing over 99.9 percent of its euchromatin. Manual annotation revealed 880 protein coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes and 3 RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobasepairs were identified and result in gene content differences across humans. One of the unique features of chromosome 16 is its high level of segmental duplication, ranked among the highest of the human autosomes. While the segmental duplications are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events which are likely to have had an impact on the evolution of primates and human disease susceptibility.

  14. The sequence and analysis of duplication rich human chromosome 16

    Energy Technology Data Exchange (ETDEWEB)

    Martin, J; Han, C; Gordon, L A; Terry, A; Prabhakar, S; She, X; Xie, G; Hellsten, U; Chan, Y M; Altherr, M; Couronne, O; Aerts, A; Bajorek, E; Black, S; Blumer, H; Branscomb, E; Brown, N; Bruno, W J; Buckingham, J; Callen, D F; Campbell, C S; Campbell, M L; Campbell, E W; Caoile, C; Challacombe, J F; Chasteen, L A; Chertkov, O; Chi, H C; Christensen, M; Clark, L M; Cohn, J D; Denys, M; Detter, J C; Dickson, M; Dimitrijevic-Bussod, M; Escobar, J; Fawcett, J J; Flowers, D; Fotopulos, D; Glavina, T; Gomez, M; Gonzales, E; Goodstein, D; Goodwin, L A; Grady, D L; Grigoriev, I; Groza, M; Hammon, N; Hawkins, T; Haydu, L; Hildebrand, C E; Huang, W; Israni, S; Jett, J; Jewett, P B; Kadner, K; Kimball, H; Kobayashi, A; Krawczyk, M; Leyba, T; Longmire, J L; Lopez, F; Lou, Y; Lowry, S; Ludeman, T; Manohar, C F; Mark, G A; McMurray, K L; Meincke, L J; Morgan, J; Moyzis, R K; Mundt, M O; Munk, A C; Nandkeshwar, R D; Pitluck, S; Pollard, M; Predki, P; Parson-Quintana, B; Ramirez, L; Rash, S; Retterer, J; Ricke, D O; Robinson, D; Rodriguez, A; Salamov, A; Saunders, E H; Scott, D; Shough, T; Stallings, R L; Stalvey, M; Sutherland, R D; Tapia, R; Tesmer, J G; Thayer, N; Thompson, L S; Tice, H; Torney, D C; Tran-Gyamfi, M; Tsai, M; Ulanovsky, L E; Ustaszewska, A; Vo, N; White, P S; Williams, A L; Wills, P L; Wu, J; Wu, K; Yang, J; DeJong, P; Bruce, D; Doggett, N A; Deaven, L; Schmutz, J; Grimwood, J; Richardson, P; Rokhsar, D S; Eichler, E E; Gilna, P; Lucas, S M; Myers, R M; Rubin, E M; Pennacchio, L A

    2005-04-06

    Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,637 aligned transcripts, 19 tRNA genes, 341 pseudogenes, and 3 RNA pseudogenes. These genes include metallothionein, cadherin, and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. While the segmental duplications of chromosome 16 are enriched in the relatively gene poor pericentromere of the p-arm, some are involved in recent gene duplication and conversion events likely to have had an impact on the evolution of primates and human disease susceptibility.

  15. Finding all sorting tandem duplication random loss operations

    DEFF Research Database (Denmark)

    Bernt, Matthias; Chen, Kuan Yu; Chen, Ming Chiang

    2011-01-01

    A tandem duplication random loss (TDRL) operation duplicates a contiguous segment of genes, followed by the random loss of one copy of each of the duplicated genes. Although the importance of this operation is founded by several recent biological studies, it has been investigated only rarely from...... a theoretical point of view. Of particular interest are sorting TDRLs which are TDRLs that, when applied to a permutation representing a genome, reduce the distance towards another given permutation. The identification of sorting genome rearrangement operations in general is a key ingredient of many algorithms...

  16. Detection of tandam duplications and implications for linkage analysis

    Energy Technology Data Exchange (ETDEWEB)

    Matise, T.C.; Weeks, D.E. (Univ. of Pittsburgh, PA (United States)); Chakravarti, A. (Case Western Reserve Univ., Cleveland, OH (United States)); Patel, P.I.; Lupski, J.R. (Baylor College of Medicine, Houston, TX (United States)); Nelis, E.; Timmerman, V.; Van Broeckhoven, C. (Univ. of Antwerp (Belgium))

    1994-06-01

    The first demonstration of an autosomal dominant human disease caused by segmental trisomy came in 1991 for Charcot-Marie-Tooth disease type 1A (CMT1A). For this disorder, the segmental trisomy is due to a large tandem duplication of 1.5 Mb of DNA located on chromosome 17p11.2-p12. The search for the CMT1A disease gene was misdirected and impeded because some chromosome 17 genetic markers that are linked to CMT1A lie within this duplication. To better understand how such a duplication might affect genetic analyses in the context of disease gene mapping, the authors studied the effects of marker duplication on transmission probabilities of marker alleles, on linkage analysis of an autosomal dominant disease, and on tests of linkage homogeneity. They demonstrate that the undetected presence of a duplication distorts transmission ratios, hampers fine localization of the disease gene, and increases false evidence of linkage heterogeneity. In addition, they devised a likelihood-based method for detecting the presence of a tandemly duplicated marker when one is suspected. They tested their methods through computer simulations and on CMT1A pedigrees genotyped at several chromosome 17 markers. On the simulated data, the method detected 96% of duplicated markers (with a false-positive rate of 5%). On the CMT1A data the method successfully identified two of three loci that are duplicated (with no false positives). This method could be used to identify duplicated markers in other regions of the genome and could be used to delineate the extent of duplications similar to that involved in CMT1A. 18 refs., 5 figs., 6 tabs.

  17. A survey of innovation through duplication in the reduced genomes of twelve parasites.

    Directory of Open Access Journals (Sweden)

    Jeremy D DeBarry

    Full Text Available We characterize the prevalence, distribution, divergence, and putative functions of detectable two-copy paralogs and segmental duplications in the Apicomplexa, a phylum of parasitic protists. Apicomplexans are mostly obligate intracellular parasites responsible for human and animal diseases (e.g. malaria and toxoplasmosis. Gene loss is a major force in the phylum. Genomes are small and protein-encoding gene repertoires are reduced. Despite this genomic streamlining, duplications and gene family amplifications are present. The potential for innovation introduced by duplications is of particular interest. We compared genomes of twelve apicomplexans across four lineages and used orthology and genome cartography to map distributions of duplications against genome architectures. Segmental duplications appear limited to five species. Where present, they correspond to regions enriched for multi-copy and species-specific genes, pointing toward roles in adaptation and innovation. We found a phylum-wide association of duplications with dynamic chromosome regions and syntenic breakpoints. Trends in the distribution of duplicated genes indicate that recent, species-specific duplicates are often tandem while most others have been dispersed by genome rearrangements. These trends show a relationship between genome architecture and gene duplication. Functional analysis reveals: proteases, which are vital to a parasitic lifecycle, to be prominent in putative recent duplications; a pair of paralogous genes in Toxoplasma gondii previously shown to produce the rate-limiting step in dopamine synthesis in mammalian cells, a possible link to the modification of host behavior; and phylum-wide differences in expression and subcellular localization, indicative of modes of divergence. We have uncovered trends in multiple modes of duplicate divergence including sequence, intron content, expression, subcellular localization, and functions of putative recent duplicates that

  18. Human-specific duplication and mosaic transcripts: the recent paralogous structure of chromosome 22.

    Science.gov (United States)

    Bailey, Jeffrey A; Yavor, Amy M; Viggiano, Luigi; Misceo, Doriana; Horvath, Juliann E; Archidiacono, Nicoletta; Schwartz, Stuart; Rocchi, Mariano; Eichler, Evan E

    2002-01-01

    In recent decades, comparative chromosomal banding, chromosome painting, and gene-order studies have shown strong conservation of gross chromosome structure and gene order in mammals. However, findings from the human genome sequence suggest an unprecedented degree of recent (homologous duplications (> or = 1 kb and > or = 90%) on chromosome 22. Overall, 10.8% (3.7/33.8 Mb) of chromosome 22 is duplicated, with an average sequence identity of 95.4%. To organize the duplications into tractable units, intron-exon structure and well-defined duplication boundaries were used to define 78 duplicated modules (minimally shared evolutionary segments) with 157 copies on chromosome 22. Analysis of these modules provides evidence for the creation or modification of 11 novel transcripts. Comparative FISH analyses of human, chimpanzee, gorilla, orangutan, and macaque reveal qualitative and quantitative differences in the distribution of these duplications--consistent with their recent origin. Several duplications appear to be human specific, including a approximately 400-kb duplication (99.4%-99.8% sequence identity) that transposed from chromosome 14 to the most proximal pericentromeric region of chromosome 22. Experimental and in silico data further support a pericentromeric gradient of duplications where the most recent duplications transpose adjacent to the centromere. Taken together, these data suggest that segmental duplications have been an ongoing process of primate genome evolution, contributing to recent gene innovation and the dynamic transformation of genome architecture within and among closely related species.

  19. A computational method for estimating the PCR duplication rate in DNA and RNA-seq experiments.

    Science.gov (United States)

    Bansal, Vikas

    2017-03-14

    PCR amplification is an important step in the preparation of DNA sequencing libraries prior to high-throughput sequencing. PCR amplification introduces redundant reads in the sequence data and estimating the PCR duplication rate is important to assess the frequency of such reads. Existing computational methods do not distinguish PCR duplicates from "natural" read duplicates that represent independent DNA fragments and therefore, over-estimate the PCR duplication rate for DNA-seq and RNA-seq experiments. In this paper, we present a computational method to estimate the average PCR duplication rate of high-throughput sequence datasets that accounts for natural read duplicates by leveraging heterozygous variants in an individual genome. Analysis of simulated data and exome sequence data from the 1000 Genomes project demonstrated that our method can accurately estimate the PCR duplication rate on paired-end as well as single-end read datasets which contain a high proportion of natural read duplicates. Further, analysis of exome datasets prepared using the Nextera library preparation method indicated that 45-50% of read duplicates correspond to natural read duplicates likely due to fragmentation bias. Finally, analysis of RNA-seq datasets from individuals in the 1000 Genomes project demonstrated that 70-95% of read duplicates observed in such datasets correspond to natural duplicates sampled from genes with high expression and identified outlier samples with a 2-fold greater PCR duplication rate than other samples. The method described here is a useful tool for estimating the PCR duplication rate of high-throughput sequence datasets and for assessing the fraction of read duplicates that correspond to natural read duplicates. An implementation of the method is available at https://github.com/vibansal/PCRduplicates .

  20. Large inverted duplications in the human genome form via a fold-back mechanism.

    Directory of Open Access Journals (Sweden)

    Karen E Hermetz

    2014-01-01

    Full Text Available Inverted duplications are a common type of copy number variation (CNV in germline and somatic genomes. Large duplications that include many genes can lead to both neurodevelopmental phenotypes in children and gene amplifications in tumors. There are several models for inverted duplication formation, most of which include a dicentric chromosome intermediate followed by breakage-fusion-bridge (BFB cycles, but the mechanisms that give rise to the inverted dicentric chromosome in most inverted duplications remain unknown. Here we have combined high-resolution array CGH, custom sequence capture, next-generation sequencing, and long-range PCR to analyze the breakpoints of 50 nonrecurrent inverted duplications in patients with intellectual disability, autism, and congenital anomalies. For half of the rearrangements in our study, we sequenced at least one breakpoint junction. Sequence analysis of breakpoint junctions reveals a normal-copy disomic spacer between inverted and non-inverted copies of the duplication. Further, short inverted sequences are present at the boundary of the disomic spacer and the inverted duplication. These data support a mechanism of inverted duplication formation whereby a chromosome with a double-strand break intrastrand pairs with itself to form a "fold-back" intermediate that, after DNA replication, produces a dicentric inverted chromosome with a disomic spacer corresponding to the site of the fold-back loop. This process can lead to inverted duplications adjacent to terminal deletions, inverted duplications juxtaposed to translocations, and inverted duplication ring chromosomes.

  1. Small Homologous Blocks in Phytophthora Genomes Do Not Point to an Ancient Whole-Genome Duplication

    NARCIS (Netherlands)

    Hooff, van J.J.E.; Snel, B.; Seidl, M.F.

    2014-01-01

    Genomes of the plant-pathogenic genus Phytophthora are characterized by small duplicated blocks consisting of two consecutive genes (2HOM blocks) and by an elevated abundance of similarly aged gene duplicates. Both properties, in particular the presence of 2HOM blocks, have been attributed to a whol

  2. Small homologous blocks in phytophthora genomes do not oint to an ancient whole-genome duplication

    NARCIS (Netherlands)

    Van Hooff, Jolien J E; Snel, Berend; Seidl, Michael F.

    2014-01-01

    Genomes of the plant-pathogenic genus Phytophthora are characterized by small duplicated blocks consisting of two consecutive genes (2HOM blocks) as well as by an elevated abundance of similarly aged gene duplicates. Both properties, in particular the presences of 2HOM blocks, have been attributed t

  3. Partial 1q Duplications and Associated Phenotype

    Science.gov (United States)

    Morris, Marcos L.M.; Baroneza, José E.; Teixeira, Patricia; Medina, Cristina T.N.; Cordoba, Mara S.; Versiani, Beatriz R.; Roese, Liege L.; Freitas, Erika L.; Fonseca, Ana C.S.; dos Santos, Maria C.G.; Pic-Taylor, Aline; Rosenberg, Carla; Oliveira, Silviene F.; Ferrari, Iris; Mazzeu, Juliana F.

    2016-01-01

    Duplications of the long arm of chromosome 1 are rare. Distal duplications are the most common and have been reported as either pure trisomy or unbalanced translocations. The paucity of cases with pure distal 1q duplications has made it difficult to delineate a partial distal trisomy 1q syndrome. Here, we report 2 patients with overlapping 1q duplications detected by G-banding. Array CGH and FISH were performed to characterize the duplicated segments, exclude the involvement of other chromosomes and determine the orientation of the duplication. Patient 1 presents with a mild phenotype and carries a 22.5-Mb 1q41q43 duplication. Patient 2 presents with a pure 1q42.13qter inverted duplication of 21.5 Mb, one of the smallest distal 1q duplications ever described and one of the few cases characterized by array CGH, thus contributing to a better characterization of distal 1q duplication syndrome. PMID:27022331

  4. Myostatin-2 gene structure and polymorphism of the promoter and first intron in the marine fish Sparus aurata: evidence for DNA duplications and/or translocations

    Directory of Open Access Journals (Sweden)

    Funkenstein Bruria

    2011-02-01

    Full Text Available Abstract Background Myostatin (MSTN is a member of the transforming growth factor-ß superfamily that functions as a negative regulator of skeletal muscle development and growth in mammals. Fish express at least two genes for MSTN: MSTN-1 and MSTN-2. To date, MSTN-2 promoters have been cloned only from salmonids and zebrafish. Results Here we described the cloning and sequence analysis of MSTN-2 gene and its 5' flanking region in the marine fish Sparus aurata (saMSTN-2. We demonstrate the existence of three alleles of the promoter and three alleles of the first intron. Sequence comparison of the promoter region in the three alleles revealed that although the sequences of the first 1050 bp upstream of the translation start site are almost identical in the three alleles, a substantial sequence divergence is seen further upstream. Careful sequence analysis of the region upstream of the first 1050 bp in the three alleles identified several elements that appear to be repeated in some or all sequences, at different positions. This suggests that the promoter region of saMSTN-2 has been subjected to various chromosomal rearrangements during the course of evolution, reflecting either insertion or deletion events. Screening of several genomic DNA collections indicated differences in allele frequency, with allele 'b' being the most abundant, followed by allele 'c', whereas allele 'a' is relatively rare. Sequence analysis of saMSTN-2 gene also revealed polymorphism in the first intron, identifying three alleles. The length difference in alleles '1R' and '2R' of the first intron is due to the presence of one or two copies of a repeated block of approximately 150 bp, located at the 5' end of the first intron. The third allele, '4R', has an additional insertion of 323 bp located 116 bp upstream of the 3' end of the first intron. Analysis of several DNA collections showed that the '2R' allele is the most common, followed by the '4R' allele, whereas the '1R

  5. Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes.

    Directory of Open Access Journals (Sweden)

    Todd J Treangen

    Full Text Available Gene duplication followed by neo- or sub-functionalization deeply impacts the evolution of protein families and is regarded as the main source of adaptive functional novelty in eukaryotes. While there is ample evidence of adaptive gene duplication in prokaryotes, it is not clear whether duplication outweighs the contribution of horizontal gene transfer in the expansion of protein families. We analyzed closely related prokaryote strains or species with small genomes (Helicobacter, Neisseria, Streptococcus, Sulfolobus, average-sized genomes (Bacillus, Enterobacteriaceae, and large genomes (Pseudomonas, Bradyrhizobiaceae to untangle the effects of duplication and horizontal transfer. After removing the effects of transposable elements and phages, we show that the vast majority of expansions of protein families are due to transfer, even among large genomes. Transferred genes--xenologs--persist longer in prokaryotic lineages possibly due to a higher/longer adaptive role. On the other hand, duplicated genes--paralogs--are expressed more, and, when persistent, they evolve slower. This suggests that gene transfer and gene duplication have very different roles in shaping the evolution of biological systems: transfer allows the acquisition of new functions and duplication leads to higher gene dosage. Accordingly, we show that paralogs share most protein-protein interactions and genetic regulators, whereas xenologs share very few of them. Prokaryotes invented most of life's biochemical diversity. Therefore, the study of the evolution of biology systems should explicitly account for the predominant role of horizontal gene transfer in the diversification of protein families.

  6. Modeling protein network evolution under genome duplication and domain shuffling

    Directory of Open Access Journals (Sweden)

    Isambert Hervé

    2007-11-01

    Full Text Available Abstract Background Successive whole genome duplications have recently been firmly established in all major eukaryote kingdoms. Such exponential evolutionary processes must have largely contributed to shape the topology of protein-protein interaction (PPI networks by outweighing, in particular, all time-linear network growths modeled so far. Results We propose and solve a mathematical model of PPI network evolution under successive genome duplications. This demonstrates, from first principles, that evolutionary conservation and scale-free topology are intrinsically linked properties of PPI networks and emerge from i prevailing exponential network dynamics under duplication and ii asymmetric divergence of gene duplicates. While required, we argue that this asymmetric divergence arises, in fact, spontaneously at the level of protein-binding sites. This supports a refined model of PPI network evolution in terms of protein domains under exponential and asymmetric duplication/divergence dynamics, with multidomain proteins underlying the combinatorial formation of protein complexes. Genome duplication then provides a powerful source of PPI network innovation by promoting local rearrangements of multidomain proteins on a genome wide scale. Yet, we show that the overall conservation and topology of PPI networks are robust to extensive domain shuffling of multidomain proteins as well as to finer details of protein interaction and evolution. Finally, large scale features of direct and indirect PPI networks of S. cerevisiae are well reproduced numerically with only two adjusted parameters of clear biological significance (i.e. network effective growth rate and average number of protein-binding domains per protein. Conclusion This study demonstrates the statistical consequences of genome duplication and domain shuffling on the conservation and topology of PPI networks over a broad evolutionary scale across eukaryote kingdoms. In particular, scale

  7. Population structure and comparative genome hybridization of European flor yeast reveal a unique group of Saccharomyces cerevisiae strains with few gene duplications in their genome.

    Science.gov (United States)

    Legras, Jean-Luc; Erny, Claude; Charpentier, Claudine

    2014-01-01

    Wine biological aging is a wine making process used to produce specific beverages in several countries in Europe, including Spain, Italy, France, and Hungary. This process involves the formation of a velum at the surface of the wine. Here, we present the first large scale comparison of all European flor strains involved in this process. We inferred the population structure of these European flor strains from their microsatellite genotype diversity and analyzed their ploidy. We show that almost all of these flor strains belong to the same cluster and are diploid, except for a few Spanish strains. Comparison of the array hybridization profile of six flor strains originating from these four countries, with that of three wine strains did not reveal any large segmental amplification. Nonetheless, some genes, including YKL221W/MCH2 and YKL222C, were amplified in the genome of four out of six flor strains. Finally, we correlated ICR1 ncRNA and FLO11 polymorphisms with flor yeast population structure, and associate the presence of wild type ICR1 and a long Flo11p with thin velum formation in a cluster of Jura strains. These results provide new insight into the diversity of flor yeast and show that combinations of different adaptive changes can lead to an increase of hydrophobicity and affect velum formation.

  8. Population structure and comparative genome hybridization of European flor yeast reveal a unique group of Saccharomyces cerevisiae strains with few gene duplications in their genome.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Legras

    Full Text Available Wine biological aging is a wine making process used to produce specific beverages in several countries in Europe, including Spain, Italy, France, and Hungary. This process involves the formation of a velum at the surface of the wine. Here, we present the first large scale comparison of all European flor strains involved in this process. We inferred the population structure of these European flor strains from their microsatellite genotype diversity and analyzed their ploidy. We show that almost all of these flor strains belong to the same cluster and are diploid, except for a few Spanish strains. Comparison of the array hybridization profile of six flor strains originating from these four countries, with that of three wine strains did not reveal any large segmental amplification. Nonetheless, some genes, including YKL221W/MCH2 and YKL222C, were amplified in the genome of four out of six flor strains. Finally, we correlated ICR1 ncRNA and FLO11 polymorphisms with flor yeast population structure, and associate the presence of wild type ICR1 and a long Flo11p with thin velum formation in a cluster of Jura strains. These results provide new insight into the diversity of flor yeast and show that combinations of different adaptive changes can lead to an increase of hydrophobicity and affect velum formation.

  9. In silico reversal of repeat-induced point mutation (RIP identifies the origins of repeat families and uncovers obscured duplicated genes

    Directory of Open Access Journals (Sweden)

    Hane James K

    2010-11-01

    Full Text Available Abstract Background Repeat-induced point mutation (RIP is a fungal genome defence mechanism guarding against transposon invasion. RIP mutates the sequence of repeated DNA and over time renders the affected regions unrecognisable by similarity search tools such as BLAST. Results DeRIP is a new software tool developed to predict the original sequence of a RIP-mutated region prior to the occurrence of RIP. In this study, we apply deRIP to the genome of the wheat pathogen Stagonospora nodorum SN15 and predict the origin of several previously uncharacterised classes of repetitive DNA. Conclusions Five new classes of transposon repeats and four classes of endogenous gene repeats were identified after deRIP. The deRIP process is a new tool for fungal genomics that facilitates the identification and understanding of the role and origin of fungal repetitive DNA. DeRIP is open-source and is available as part of the RIPCAL suite at http://www.sourceforge.net/projects/ripcal.

  10. FT Duplication Coordinates Reproductive and Vegetative Growth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Chuan-Yu [Mississippi State University (MSU); Adams, Joshua P. [Mississippi State University (MSU); Kim, Hyejin [Mississippi State University (MSU); No, Kyoungok [Mississippi State University (MSU); Ma, Caiping [Oregon State University, Corvallis; Strauss, Steven [Oregon State University, Corvallis; Drnevich, Jenny [University of Illinois, Urbana-Champaign; Wickett, Norman [Pennsylvania State University; Vandervelde, Lindsay [Mississippi State University (MSU); Ellis, Jeffrey D. [Mississippi State University (MSU); Rice, Brandon [Mississippi State University (MSU); Gunter, Lee E [ORNL; Tuskan, Gerald A [ORNL; Brunner, Amy M. [Virginia Polytechnic Institute and State University (Virginia Tech); Page, Grier P. [RTI International; Carlson, John E. [Pennsylvania State University; DePamphilis, Claude [Pennsylvania State University; Luthe, Dawn S. [Pennsylvania State University; Yuceer, Cetin [Mississippi State University (MSU)

    2011-01-01

    Annual plants grow vegetatively at early developmental stages and then transition to the reproductive stage, followed by senescence in the same year. In contrast, after successive years of vegetative growth at early ages, woody perennial shoot meristems begin repeated transitions between vegetative and reproductive growth at sexual maturity. However, it is unknown how these repeated transitions occur without a developmental conflict between vegetative and reproductive growth. We report that functionally diverged paralogs FLOWERING LOCUS T1 (FT1) and FLOWERING LOCUS T2 (FT2), products of whole-genome duplication and homologs of Arabidopsis thaliana gene FLOWERING LOCUS T (FT), coordinate the repeated cycles of vegetative and reproductive growth in woody perennial poplar (Populus spp.). Our manipulative physiological and genetic experiments coupled with field studies, expression profiling, and network analysis reveal that reproductive onset is determined by FT1 in response to winter temperatures, whereas vegetative growth and inhibition of bud set are promoted by FT2 in response to warm temperatures and long days in the growing season. The basis for functional differentiation between FT1 and FT2 appears to be expression pattern shifts, changes in proteins, and divergence in gene regulatory networks. Thus, temporal separation of reproductive onset and vegetative growth into different seasons via FT1 and FT2 provides seasonality and demonstrates the evolution of a complex perennial adaptive trait after genome duplication.

  11. Intrathoracic enteric foregut duplication cyst.

    Directory of Open Access Journals (Sweden)

    Birmole B

    1994-10-01

    Full Text Available A one month old male child presented with respiratory distress since day 10 of life. There was intercostal retraction and decreased air entry on the right side. Investigations revealed a well defined cystic mass in the posterior mediastinum with vertebral anomalies, the cyst was excised by posterolateral thoracotomy. Histopathology revealed it to be an enteric foregut duplication cyst.

  12. Horizontal Transfer, Not Duplication, Drives the Expansion of Protein Families in Prokaryotes

    Science.gov (United States)

    Treangen, Todd J.; Rocha, Eduardo P. C.

    2011-01-01

    Gene duplication followed by neo- or sub-functionalization deeply impacts the evolution of protein families and is regarded as the main source of adaptive functional novelty in eukaryotes. While there is ample evidence of adaptive gene duplication in prokaryotes, it is not clear whether duplication outweighs the contribution of horizontal gene transfer in the expansion of protein families. We analyzed closely related prokaryote strains or species with small genomes (Helicobacter, Neisseria, Streptococcus, Sulfolobus), average-sized genomes (Bacillus, Enterobacteriaceae), and large genomes (Pseudomonas, Bradyrhizobiaceae) to untangle the effects of duplication and horizontal transfer. After removing the effects of transposable elements and phages, we show that the vast majority of expansions of protein families are due to transfer, even among large genomes. Transferred genes—xenologs—persist longer in prokaryotic lineages possibly due to a higher/longer adaptive role. On the other hand, duplicated genes—paralogs—are expressed more, and, when persistent, they evolve slower. This suggests that gene transfer and gene duplication have very different roles in shaping the evolution of biological systems: transfer allows the acquisition of new functions and duplication leads to higher gene dosage. Accordingly, we show that paralogs share most protein–protein interactions and genetic regulators, whereas xenologs share very few of them. Prokaryotes invented most of life's biochemical diversity. Therefore, the study of the evolution of biology systems should explicitly account for the predominant role of horizontal gene transfer in the diversification of protein families. PMID:21298028

  13. Intragenic duplication: a novel mutational mechanism in hereditary pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, Maiken T; Geisz, Andrea; Brusgaard, Klaus

    2011-01-01

    In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide of cationic...

  14. Targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae.

    Science.gov (United States)

    Takahashi, Tadashi; Sato, Atsushi; Ogawa, Masahiro; Hanya, Yoshiki; Oguma, Tetsuya

    2014-08-01

    We describe here the first successful construction of a targeted tandem duplication of a large chromosomal segment in Aspergillus oryzae. The targeted tandem chromosomal duplication was achieved by using strains that had a 5'-deleted pyrG upstream of the region targeted for tandem chromosomal duplication and a 3'-deleted pyrG downstream of the target region. Consequently,strains bearing a 210-kb targeted tandem chromosomal duplication near the centromeric region of chromosome 8 and strains bearing a targeted tandem chromosomal duplication of a 700-kb region of chromosome 2 were successfully constructed. The strains bearing the tandem chromosomal duplication were efficiently obtained from the regenerated protoplast of the parental strains. However, the generation of the chromosomal duplication did not depend on the introduction of double-stranded breaks(DSBs) by I-SceI. The chromosomal duplications of these strains were stably maintained after five generations of culture under nonselective conditions. The strains bearing the tandem chromosomal duplication in the 700-kb region of chromosome 2 showed highly increased protease activity in solid-state culture, indicating that the duplication of large chromosomal segments could be a useful new breeding technology and gene analysis method.

  15. The hidden duplication past of the plant pathogen Phytophthora and its consequences for infection

    Directory of Open Access Journals (Sweden)

    Martens Cindy

    2010-06-01

    Full Text Available Abstract Background Oomycetes of the genus Phytophthora are pathogens that infect a wide range of plant species. For dicot hosts such as tomato, potato and soybean, Phytophthora is even the most important pathogen. Previous analyses of Phytophthora genomes uncovered many genes, large gene families and large genome sizes that can partially be explained by significant repeat expansion patterns. Results Analysis of the complete genomes of three different Phytophthora species, using a newly developed approach, unveiled a large number of small duplicated blocks, mainly consisting of two or three consecutive genes. Further analysis of these duplicated genes and comparison with the known gene and genome duplication history of ten other eukaryotes including parasites, algae, plants, fungi, vertebrates and invertebrates, suggests that the ancestor of P. infestans, P. sojae and P. ramorum most likely underwent a whole genome duplication (WGD. Genes that have survived in duplicate are mainly genes that are known to be preferentially retained following WGDs, but also genes important for pathogenicity and infection of the different hosts seem to have been retained in excess. As a result, the WGD might have contributed to the evolutionary and pathogenic success of Phytophthora. Conclusions The fact that we find many small blocks of duplicated genes indicates that the genomes of Phytophthora species have been heavily rearranged following the WGD. Most likely, the high repeat content in these genomes have played an important role in this rearrangement process. As a consequence, the paucity of retained larger duplicated blocks has greatly complicated previous attempts to detect remnants of a large-scale duplication event in Phytophthora. However, as we show here, our newly developed strategy to identify very small duplicated blocks might be a useful approach to uncover ancient polyploidy events, in particular for heavily rearranged genomes.

  16. Comparative genomic analysis of duplicated homoeologous regions involved in the resistance of Brassica napus to stem canker

    Directory of Open Access Journals (Sweden)

    Berline eFopa Fomeju

    2015-09-01

    Full Text Available All crop species are current or ancient polyploids. Following whole genome duplication, structural and functional modifications result in differential gene content or regulation in the duplicated regions, which can play a fundamental role in the diversification of genes underlying complex traits. We have investigated this issue in Brassica napus, a species with a highly duplicated genome, with the aim of studying the structural and functional organization of duplicated regions involved in quantitative resistance to stem canker, a disease caused by the fungal pathogen Leptosphaeria maculans. Genome-wide association analysis on two oilseed rape panels confirmed that duplicated regions of ancestral blocks E, J, R, U and W were involved in resistance to stem canker. The structural analysis of the duplicated genomic regions showed a higher gene density on the A genome than on the C genome and a better collinearity between homoeologous regions than paralogous regions, as overall in the whole B. napus genome. The three ancestral sub-genomes were involved in the resistance to stem canker and the fractionation profile of the duplicated regions corresponded to what was expected from results on the B. napus progenitors. About 60% of the genes identified in these duplicated regions were single-copy genes while less than 5% were retained in all the duplicated copies of a given ancestral block. Genes retained in several copies were mainly involved in response to stress, signaling or transcription regulation. Genes with resistance-associated markers were mainly retained in more than two copies. These results suggested that some genes underlying quantitative resistance to stem canker might be duplicated genes. Genes with a hydrolase activity that were retained in one copy or R-like genes might also account for resistance in some regions. Further analyses need to be conducted to indicate to what extent duplicated genes contribute to the expression of the

  17. Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukemia study.

    Science.gov (United States)

    Lucena-Araujo, Antonio R; Kim, Haesook T; Jacomo, Rafael H; Melo, Raul A; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Fagundes, Evandro M; Chauffaille, Maria de Lourdes; Chiattone, Carlos S; Lima, Ana Silvia; Ruiz-Argüelles, Guillermo; Undurraga, Maria Soledad; Martinez, Lem; Kwaan, Hau C; Gallagher, Robert; Niemeyer, Charlotte M; Schrier, Stanley L; Tallman, Martin S; Grimwade, David; Ganser, Arnold; Berliner, Nancy; Ribeiro, Raul C; Lo-Coco, Francesco; Löwenberg, Bob; Sanz, Miguel A; Rego, Eduardo M

    2014-12-01

    Activating internal tandem duplication (ITD) mutations in the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor outcome in acute myeloid leukemia, but their prognostic impact in acute promyelocytic leukemia (APL) remains controversial. Here, we screened for FLT3-ITD mutations in 171 APL patients, treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. We identified FLT3-ITD mutations in 35 patients (20 %). FLT3-ITD mutations were associated with higher white blood cell counts (P < 0.0001), relapse-risk score (P = 0.0007), higher hemoglobin levels (P = 0.0004), higher frequency of the microgranular morphology (M3v) subtype (P = 0.03), and the short PML/RARA (BCR3) isoform (P < 0.0001). After a median follow-up of 38 months, FLT3-ITD(positive) patients had a lower 3-year overall survival rate (62 %) compared with FLT3-ITD(negative) patients (82 %) (P = 0.006). The prognostic impact of FLT3-ITD on survival was retained in multivariable analysis (hazard ratio: 2.39, 95 % confidence interval [CI] 1.17-4.89; P = 0.017). Nevertheless, complete remission (P = 0.07), disease-free survival (P = 0.24), and the cumulative incidence of relapse (P = 0.94) rates were not significantly different between groups. We can conclude that FLT3-ITD mutations are associated with several hematologic features in APL, in particular with high white blood cell counts. In addition, FLT3-ITD may independently predict a shorter survival in patients with APL treated with ATRA and anthracycline-based chemotherapy.

  18. Genome duplication, subfunction partitioning, and lineage divergence: Sox9 in stickleback and zebrafish.

    Science.gov (United States)

    Cresko, William A; Yan, Yi-Lin; Baltrus, David A; Amores, Angel; Singer, Amy; Rodríguez-Marí, Adriana; Postlethwait, John H

    2003-11-01

    Teleosts are the most species-rich group of vertebrates, and a genome duplication (tetraploidization) event in ray-fin fish appears to have preceded this remarkable explosion of biodiversity. What is the relationship of the ray-fin genome duplication to the teleost radiation? Genome duplication may have facilitated lineage divergence by partitioning different ancestral gene subfunctions among co-orthologs of tetrapod genes in different teleost lineages. To test this hypothesis, we investigated gene expression patterns for Sox9 gene duplicates in stickleback and zebrafish, teleosts whose lineages diverged early in Euteleost evolution. Most expression domains appear to have been partitioned between Sox9a and Sox9b before the divergence of stickleback and zebrafish lineages, but some ancestral expression domains were distributed differentially in each lineage. We conclude that some gene subfunctions, as represented by lineage-specific expression domains, may have assorted differently in separate lineages and that these may have contributed to lineage diversification during teleost evolution.

  19. Congenital duplication of the gallbladder.

    Science.gov (United States)

    Safioleas, Michael C; Papavassiliou, Vassilios G; Moulakakis, Konstantinos G; Angouras, Dimitrios C; Skandalakis, Panagiotis

    2006-03-01

    Duplication of the gallbladder is a rare congenital anomaly of the biliary system. In this article, two cases of gallbladder duplication are presented. The first case is a patient with double gallbladder and concomitant choledocholithiasis. The probable diagnosis of double gallbladder was made preoperatively by computed tomography. The patient underwent a successful open cholecystectomy and common bile duct exploration. In the second case, two cystic formations in the place of gallbladder are demonstrated with ultrasound scan in a woman with acute cholecystitis. At surgery, two gallbladders were found. A brief review of epidemiology and anatomy of double gallbladder is included, along with a discussion of the difficulties in diagnosis and treatment of this condition.

  20. Clustering of diverse replicated sequences in the MHC: Evidence for en bloc duplication

    Energy Technology Data Exchange (ETDEWEB)

    Leelayuwat, C.; Pinelli, M. [Univ. Western Australia, Perth (Australia); Dawkins, R.L. [Royal Perth Hospital (Australia)

    1995-07-15

    The MHC contains clusters of polymorphic duplicated genes and gene sequences. It has been thought that these duplicated genes and sequences have arisen from single gene duplications. We compared the cloned region between TNF and HLA-B with the region in close proximity to HLA-A using sequence analysis and DNA hybridization. The results indicate that several sequences existing in the region centromeric of HLA-B are also present in close proximity to HLA-A. These include sequences belonging to the P5, BAT1, and PERB11 gene families as well as HLA class I gene sequences. Interestingly, when the two regions of approximately 200 kilobases are compared, the replicated sequences are organized similarly but in an inverted fashion suggesting the existence of an historical inverted en bloc duplication. Thus, we propose that the origin of these MHC gene clusters involves several mechanisms. In addition to single gene replication, a long-range duplication of a genomic block must have occurred. It is possible that a block at the telomeric end of the MHC represents a basic functional genomic unit conserved and duplicated en bloc. 49 refs., 3 figs., 3 tabs.

  1. Tubular Colonic Duplication Presenting as Rectovestibular Fistula.

    Science.gov (United States)

    Karkera, Parag J; Bendre, Pradnya; D'souza, Flavia; Ramchandra, Mukunda; Nage, Amol; Palse, Nitin

    2015-09-01

    Complete colonic duplication is a very rare congenital anomaly that may have different presentations according to its location and size. Complete colonic duplication can occur in about 15% of all gastrointestinal duplications. Double termination of tubular colonic duplication in the perineum is even more uncommon. We present a case of a Y-shaped tubular colonic duplication which presented with a rectovestibular fistula and a normal anus. Radiological evaluation and initial exploration for sigmoidostomy revealed duplicated colons with a common vascular supply. Endorectal mucosal resection of theduplicated distal segment till the colostomy site with division of the septum of the proximal segment and colostomy closure proved curative without compromise of the continence mechanism. Tubular colonic duplication should always be ruled out when a diagnosis of perineal canal is considered in cases of vestibular fistula alongwith a normal anus.

  2. Tandem Duplications and the Limits of Natural Selection in Drosophila yakuba and Drosophila simulans.

    Science.gov (United States)

    Rogers, Rebekah L; Cridland, Julie M; Shao, Ling; Hu, Tina T; Andolfatto, Peter; Thornton, Kevin R

    2015-01-01

    Tandem duplications are an essential source of genetic novelty, and their variation in natural populations is expected to influence adaptive walks. Here, we describe evolutionary impacts of recently-derived, segregating tandem duplications in Drosophila yakuba and Drosophila simulans. We observe an excess of duplicated genes involved in defense against pathogens, insecticide resistance, chorion development, cuticular peptides, and lipases or endopeptidases associated with the accessory glands across both species. The observed agreement is greater than expectations on chance alone, suggesting large amounts of convergence across functional categories. We document evidence of widespread selection on the D. simulans X, suggesting adaptation through duplication is common on the X. Despite the evidence for positive selection, duplicates display an excess of low frequency variants consistent with largely detrimental impacts, limiting the variation that can effectively facilitate adaptation. Standing variation for tandem duplications spans less than 25% of the genome in D. yakuba and D. simulans, indicating that evolution will be strictly limited by mutation, even in organisms with large population sizes. Effective whole gene duplication rates are low at 1.17 × 10-9 per gene per generation in D. yakuba and 6.03 × 10-10 per gene per generation in D. simulans, suggesting long wait times for new mutations on the order of thousands of years for the establishment of sweeps. Hence, in cases where adaptation depends on individual tandem duplications, evolution will be severely limited by mutation. We observe low levels of parallel recruitment of the same duplicated gene in different species, suggesting that the span of standing variation will define evolutionary outcomes in spite of convergence across gene ontologies consistent with rapidly evolving phenotypes.

  3. Tandem Duplications and the Limits of Natural Selection in Drosophila yakuba and Drosophila simulans.

    Directory of Open Access Journals (Sweden)

    Rebekah L Rogers

    Full Text Available Tandem duplications are an essential source of genetic novelty, and their variation in natural populations is expected to influence adaptive walks. Here, we describe evolutionary impacts of recently-derived, segregating tandem duplications in Drosophila yakuba and Drosophila simulans. We observe an excess of duplicated genes involved in defense against pathogens, insecticide resistance, chorion development, cuticular peptides, and lipases or endopeptidases associated with the accessory glands across both species. The observed agreement is greater than expectations on chance alone, suggesting large amounts of convergence across functional categories. We document evidence of widespread selection on the D. simulans X, suggesting adaptation through duplication is common on the X. Despite the evidence for positive selection, duplicates display an excess of low frequency variants consistent with largely detrimental impacts, limiting the variation that can effectively facilitate adaptation. Standing variation for tandem duplications spans less than 25% of the genome in D. yakuba and D. simulans, indicating that evolution will be strictly limited by mutation, even in organisms with large population sizes. Effective whole gene duplication rates are low at 1.17 × 10-9 per gene per generation in D. yakuba and 6.03 × 10-10 per gene per generation in D. simulans, suggesting long wait times for new mutations on the order of thousands of years for the establishment of sweeps. Hence, in cases where adaptation depends on individual tandem duplications, evolution will be severely limited by mutation. We observe low levels of parallel recruitment of the same duplicated gene in different species, suggesting that the span of standing variation will define evolutionary outcomes in spite of convergence across gene ontologies consistent with rapidly evolving phenotypes.

  4. The sequence and analysis of duplication-rich human chromosome 16.

    Science.gov (United States)

    Martin, Joel; Han, Cliff; Gordon, Laurie A; Terry, Astrid; Prabhakar, Shyam; She, Xinwei; Xie, Gary; Hellsten, Uffe; Chan, Yee Man; Altherr, Michael; Couronne, Olivier; Aerts, Andrea; Bajorek, Eva; Black, Stacey; Blumer, Heather; Branscomb, Elbert; Brown, Nancy C; Bruno, William J; Buckingham, Judith M; Callen, David F; Campbell, Connie S; Campbell, Mary L; Campbell, Evelyn W; Caoile, Chenier; Challacombe, Jean F; Chasteen, Leslie A; Chertkov, Olga; Chi, Han C; Christensen, Mari; Clark, Lynn M; Cohn, Judith D; Denys, Mirian; Detter, John C; Dickson, Mark; Dimitrijevic-Bussod, Mira; Escobar, Julio; Fawcett, Joseph J; Flowers, Dave; Fotopulos, Dea; Glavina, Tijana; Gomez, Maria; Gonzales, Eidelyn; Goodstein, David; Goodwin, Lynne A; Grady, Deborah L; Grigoriev, Igor; Groza, Matthew; Hammon, Nancy; Hawkins, Trevor; Haydu, Lauren; Hildebrand, Carl E; Huang, Wayne; Israni, Sanjay; Jett, Jamie; Jewett, Phillip B; Kadner, Kristen; Kimball, Heather; Kobayashi, Arthur; Krawczyk, Marie-Claude; Leyba, Tina; Longmire, Jonathan L; Lopez, Frederick; Lou, Yunian; Lowry, Steve; Ludeman, Thom; Manohar, Chitra F; Mark, Graham A; McMurray, Kimberly L; Meincke, Linda J; Morgan, Jenna; Moyzis, Robert K; Mundt, Mark O; Munk, A Christine; Nandkeshwar, Richard D; Pitluck, Sam; Pollard, Martin; Predki, Paul; Parson-Quintana, Beverly; Ramirez, Lucia; Rash, Sam; Retterer, James; Ricke, Darryl O; Robinson, Donna L; Rodriguez, Alex; Salamov, Asaf; Saunders, Elizabeth H; Scott, Duncan; Shough, Timothy; Stallings, Raymond L; Stalvey, Malinda; Sutherland, Robert D; Tapia, Roxanne; Tesmer, Judith G; Thayer, Nina; Thompson, Linda S; Tice, Hope; Torney, David C; Tran-Gyamfi, Mary; Tsai, Ming; Ulanovsky, Levy E; Ustaszewska, Anna; Vo, Nu; White, P Scott; Williams, Albert L; Wills, Patricia L; Wu, Jung-Rung; Wu, Kevin; Yang, Joan; Dejong, Pieter; Bruce, David; Doggett, Norman A; Deaven, Larry; Schmutz, Jeremy; Grimwood, Jane; Richardson, Paul; Rokhsar, Daniel S; Eichler, Evan E; Gilna, Paul; Lucas, Susan M; Myers, Richard M; Rubin, Edward M; Pennacchio, Len A

    2004-12-23

    Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.

  5. Narrow, duplicated internal auditory canal

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, T. [Servico de Neurorradiologia, Hospital Garcia de Orta, Avenida Torrado da Silva, 2801-951, Almada (Portugal); Shayestehfar, B. [Department of Radiology, UCLA Oliveview School of Medicine, Los Angeles, California (United States); Lufkin, R. [Department of Radiology, UCLA School of Medicine, Los Angeles, California (United States)

    2003-05-01

    A narrow internal auditory canal (IAC) constitutes a relative contraindication to cochlear implantation because it is associated with aplasia or hypoplasia of the vestibulocochlear nerve or its cochlear branch. We report an unusual case of a narrow, duplicated IAC, divided by a bony septum into a superior relatively large portion and an inferior stenotic portion, in which we could identify only the facial nerve. This case adds support to the association between a narrow IAC and aplasia or hypoplasia of the vestibulocochlear nerve. The normal facial nerve argues against the hypothesis that the narrow IAC is the result of a primary bony defect which inhibits the growth of the vestibulocochlear nerve. (orig.)

  6. The evolution of developmental patterning under genetic duplication constraints

    OpenAIRE

    Fuentes, Miguel A.; Krakauer, David C

    2007-01-01

    Of considerable interest are the evolutionary and developmental origins of complex, adaptive structures and the mechanisms that stabilize these structures. We consider the relationship between the evolutionary process of gene duplication and deletion and the stability of morphogenetic patterns produced by interacting activators and inhibitors. We compare the relative stability of patterns with a single activator and inhibitor (two-dimensional system) against a ‘redundant’ system with two acti...

  7. Identification of large NF1 duplications reciprocal to NAHR-mediated type-1 NF1 deletions.

    Science.gov (United States)

    Kehrer-Sawatzki, Hildegard; Bengesser, Kathrin; Callens, Tom; Mikhail, Fady; Fu, Chuanhua; Hillmer, Morten; Walker, Martha E; Saal, Howard M; Lacassie, Yves; Cooper, David N; Messiaen, Ludwine

    2014-12-01

    Approximately 5% of all patients with neurofibromatosis type-1 (NF1) exhibit large deletions of the NF1 gene region. To date, only nine unrelated cases of large NF1 duplications have been reported, with none of the affected patients exhibiting multiple café au lait spots (CALS), Lisch nodules, freckling, or neurofibromas, the hallmark signs of NF1. Here, we have characterized two novel NF1 duplications, one sporadic and one familial. Both index patients with NF1 duplications exhibited learning disabilities and atypical CALS. Additionally, patient R609021 had Lisch nodules, whereas patient R653070 exhibited two inguinal freckles. The mother and sister of patient R609021 also harbored the NF1 duplication and exhibited cognitive dysfunction but no CALS. The breakpoints of the nine NF1 duplications reported previously have not been identified and hence their underlying generative mechanisms have remained unclear. In this study, we performed high-resolution breakpoint analysis that indicated that the two duplications studied were mediated by nonallelic homologous recombination (NAHR) and that the duplication breakpoints were located within the NAHR hotspot paralogous recombination site 2 (PRS2), which also harbors the type-1 NF1 deletion breakpoints. Hence, our study indicates for the first time that NF1 duplications are reciprocal to type-1 NF1 deletions and originate from the same NAHR events. © 2014 WILEY PERIODICALS, INC.

  8. The evolution of developmental patterning under genetic duplication constraints.

    Science.gov (United States)

    Fuentes, Miguel A; Krakauer, David C

    2008-02-06

    Of considerable interest are the evolutionary and developmental origins of complex, adaptive structures and the mechanisms that stabilize these structures. We consider the relationship between the evolutionary process of gene duplication and deletion and the stability of morphogenetic patterns produced by interacting activators and inhibitors. We compare the relative stability of patterns with a single activator and inhibitor (two-dimensional system) against a 'redundant' system with two activators or two inhibitors (three-dimensional system). We find that duplication events can both expand and contract the space of patterns. We study developmental robustness in terms of stochastic escape times from this space, also known as a 'canalization potential'. We embed the output of pattern formation into an explicit evolutionary model of gene duplication, gene loss and variation in the steepness of the canalization potential. We find that under all constant conditions, the system evolves towards a preference for steep potentials associated with low phenotypic variability and longer lifespans. This preference leads to an overall decrease in the density of redundant genotypes as developmental robustness neutralizes the advantages of genetic robustness.

  9. The detection of large deletions or duplications in genomic DNA.

    Science.gov (United States)

    Armour, J A L; Barton, D E; Cockburn, D J; Taylor, G R

    2002-11-01

    While methods for the detection of point mutations and small insertions or deletions in genomic DNA are well established, the detection of larger (>100 bp) genomic duplications or deletions can be more difficult. Most mutation scanning methods use PCR as a first step, but the subsequent analyses are usually qualitative rather than quantitative. Gene dosage methods based on PCR need to be quantitative (i.e., they should report molar quantities of starting material) or semi-quantitative (i.e., they should report gene dosage relative to an internal standard). Without some sort of quantitation, heterozygous deletions and duplications may be overlooked and therefore be under-ascertained. Gene dosage methods provide the additional benefit of reporting allele drop-out in the PCR. This could impact on SNP surveys, where large-scale genotyping may miss null alleles. Here we review recent developments in techniques for the detection of this type of mutation and compare their relative strengths and weaknesses. We emphasize that comprehensive mutation analysis should include scanning for large insertions and deletions and duplications. Copyright 2002 Wiley-Liss, Inc.

  10. MSOAR 2.0: Incorporating tandem duplications into ortholog assignment based on genome rearrangement

    Directory of Open Access Journals (Sweden)

    Zhang Liqing

    2010-01-01

    Full Text Available Abstract Background Ortholog assignment is a critical and fundamental problem in comparative genomics, since orthologs are considered to be functional counterparts in different species and can be used to infer molecular functions of one species from those of other species. MSOAR is a recently developed high-throughput system for assigning one-to-one orthologs between closely related species on a genome scale. It attempts to reconstruct the evolutionary history of input genomes in terms of genome rearrangement and gene duplication events. It assumes that a gene duplication event inserts a duplicated gene into the genome of interest at a random location (i.e., the random duplication model. However, in practice, biologists believe that genes are often duplicated by tandem duplications, where a duplicated gene is located next to the original copy (i.e., the tandem duplication model. Results In this paper, we develop MSOAR 2.0, an improved system for one-to-one ortholog assignment. For a pair of input genomes, the system first focuses on the tandemly duplicated genes of each genome and tries to identify among them those that were duplicated after the speciation (i.e., the so-called inparalogs, using a simple phylogenetic tree reconciliation method. For each such set of tandemly duplicated inparalogs, all but one gene will be deleted from the concerned genome (because they cannot possibly appear in any one-to-one ortholog pairs, and MSOAR is invoked. Using both simulated and real data experiments, we show that MSOAR 2.0 is able to achieve a better sensitivity and specificity than MSOAR. In comparison with the well-known genome-scale ortholog assignment tool InParanoid, Ensembl ortholog database, and the orthology information extracted from the well-known whole-genome multiple alignment program MultiZ, MSOAR 2.0 shows the highest sensitivity. Although the specificity of MSOAR 2.0 is slightly worse than that of InParanoid in the real data experiments

  11. "Tandem duplication-random loss" is not a real feature of oyster mitochondrial genomes

    Directory of Open Access Journals (Sweden)

    Zhang Guofan

    2009-02-01

    Full Text Available Abstract Duplications and rearrangements of coding genes are major themes in the evolution of mitochondrial genomes, bearing important consequences in the function of mitochondria and the fitness of organisms. Yu et al. (BMC Genomics 2008, 9:477 reported the complete mt genome sequence of the oyster Crassostrea hongkongensis (16,475 bp and found that a DNA segment containing four tRNA genes (trnK1, trnC, trnQ1 and trnN, a duplicated (rrnS and a split rRNA gene (rrnL5' was absent compared with that of two other Crassostrea species. It was suggested that the absence was a novel case of "tandem duplication-random loss" with evolutionary significance. We independently sequenced the complete mt genome of three C. hongkongensis individuals, all of which were 18,622 bp and contained the segment that was missing in Yu et al.'s sequence. Further, we designed primers, verified sequences and demonstrated that the sequence loss in Yu et al.'s study was an artifact caused by placing primers in a duplicated region. The duplication and split of ribosomal RNA genes are unique for Crassostrea oysters and not lost in C. hongkongensis. Our study highlights the need for caution when amplifying and sequencing through duplicated regions of the genome.

  12. Two Rounds of Whole Genome Duplication in the AncestralVertebrate

    Energy Technology Data Exchange (ETDEWEB)

    Dehal, Paramvir; Boore, Jeffrey L.

    2005-04-12

    The hypothesis that the relatively large and complex vertebrate genome was created by two ancient, whole genome duplications has been hotly debated, but remains unresolved. We reconstructed the evolutionary relationships of all gene families from the complete gene sets of a tunicate, fish, mouse, and human, then determined when each gene duplicated relative to the evolutionary tree of the organisms. We confirmed the results of earlier studies that there remains little signal of these events in numbers of duplicated genes, gene tree topology, or the number of genes per multigene family. However, when we plotted the genomic map positions of only the subset of paralogous genes that were duplicated prior to the fish-tetrapod split, their global physical organization provides unmistakable evidence of two distinct genome duplication events early in vertebrate evolution indicated by clear patterns of 4-way paralogous regions covering a large part of the human genome. Our results highlight the potential for these large-scale genomic events to have driven the evolutionary success of the vertebrate lineage.

  13. Partial Duplication of Chromosome 8p

    African Journals Online (AJOL)

    rme

    The partial chromosome 8p duplication is a rare syndrome and is ... clinical and cytogenetic data of 5 Arab patients with de novo inversion duplication of 8p. ... characterized by Fluorescent in situ ... thick lower lips, down turned angles of mouth ...

  14. Duodenal duplication cyst identified with MRCP

    Energy Technology Data Exchange (ETDEWEB)

    Carbognin, G.; Guarise, A.; Biasiutti, C.; Pagnotta, N.; Procacci, C. [Department of Radiology, University Hospital ' G.B. Rossi' , Verona (Italy)

    2000-08-01

    We report a case of a stalked cystic duodenal duplication. The lesion, hyperintense on T2-weighted GRE images, maintained the signal intensity after oral administration of a negative contrast agent (Lumirem, Guerbet, Aulnay-Sous-Bois, France), confirming its independence from the duodenal lumen. To our knowledge, this is the first demonstration of duodenal duplication by means of MR cholangiopancreatography. (orig.)

  15. Bilateral duplication of the internal auditory canal

    Energy Technology Data Exchange (ETDEWEB)

    Weon, Young Cheol; Kim, Jae Hyoung; Choi, Sung Kyu [Seoul National University College of Medicine, Department of Radiology, Seoul National University Bundang Hospital, Seongnam-si (Korea); Koo, Ja-Won [Seoul National University College of Medicine, Department of Otolaryngology, Seoul National University Bundang Hospital, Seongnam-si (Korea)

    2007-10-15

    Duplication of the internal auditory canal is an extremely rare temporal bone anomaly that is believed to result from aplasia or hypoplasia of the vestibulocochlear nerve. We report bilateral duplication of the internal auditory canal in a 28-month-old boy with developmental delay and sensorineural hearing loss. (orig.)

  16. A partial MECP2 duplication in a mildly affected adult male: a putative role for the 3' untranslated region in the MECP2 duplication phenotype

    Directory of Open Access Journals (Sweden)

    Hanchard Neil A

    2012-08-01

    Full Text Available Abstract Background Duplications of the X-linked MECP2 gene are associated with moderate to severe intellectual disability, epilepsy, and neuropsychiatric illness in males, while triplications are associated with a more severe phenotype. Most carrier females show complete skewing of X-inactivation in peripheral blood and an apparent susceptibility to specific personality traits or neuropsychiatric symptoms. Methods We describe the clinical phenotype of a pedigree segregating a duplication of MECP2 found on clinical array comparative genomic hybridization. The position, size, and extent of the duplication were delineated in peripheral blood samples from affected individuals using multiplex ligation-dependent probe amplification and fluorescence in situ hybridization, as well as targeted high-resolution oligonucleotide microarray analysis and long-range PCR. The molecular consequences of the rearrangement were studied in lymphoblast cell lines using quantitative real-time PCR, reverse transcriptase PCR, and western blot analysis. Results We observed a partial MECP2 duplication in an adult male with epilepsy and mild neurocognitive impairment who was able to function independently; this phenotype has not previously been reported among males harboring gains in MECP2 copy number. The same duplication was inherited by this individual’s daughter who was also affected with neurocognitive impairment and epilepsy and carried an additional copy-number variant. The duplicated segment involved all four exons of MECP2, but excluded almost the entire 3' untranslated region (UTR, and the genomic rearrangement resulted in a MECP2-TEX28 fusion gene mRNA transcript. Increased expression of MECP2 and the resulting fusion gene were both confirmed; however, western blot analysis of lysates from lymphoblast cells demonstrated increased MeCP2 protein without evidence of a stable fusion gene protein product. Conclusion The observations of a mildly affected adult male

  17. Current incidence of duplicate publication in otolaryngology.

    Science.gov (United States)

    Cheung, Veronique Wan Fook; Lam, Gilbert O A; Wang, Yun Fan; Chadha, Neil K

    2014-03-01

    Duplicate publication--deemed highly unethical--is the reproduction of substantial content in another article by the same authors. In 1999, Rosenthal et al. identified an 8.5% incidence of duplicate articles in two otolaryngology journals. We explored the current incidence in three otolaryngology journals in North America and Europe. Retrospective literature review. Index articles in 2008 in Archives of Otolaryngology-Head and Neck Surgery, Laryngoscope, and Clinical Otolaryngology were searched using MEDLINE. Potential duplicate publications in 2006 through 2010 were identified using the first, second, and last authors' names. Three authors independently investigated suspected duplicate publications--classifying them by degree of duplication. Of 358 index articles screened, 75 (20.9%) had 119 potential duplicates from 2006 to 2010. Full review of these 119 potential duplicates revealed a total of 40 articles with some form of redundancy (33.6% of the potential duplicates) involving 27 index articles (7.5% of 358 index articles); one (0.8%) "dual" publication (identical or nearly identical data and conclusions to the index article); three (2.5%) "suspected" dual publications (less than 50% new data and same conclusions); and 36 (30.3%) publications with "salami-slicing" (portion of the index article data repeated) were obtained. Further analysis compared the likelihood of duplicate publication by study source and subspecialty within otolaryngology. The incidence of duplicate publication has not significantly changed over 10 years. "Salami-slicing" was a concerning practice, with no cross-referencing in 61% of these cases. Detecting and eliminating redundant publications is a laborious task, but it is essential in upholding the journal quality and research integrity. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    DEFF Research Database (Denmark)

    Isles, Anthony R; Ingason, Andrés; Lowther, Chelsea

    2016-01-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may...

  19. Molecular and Population Analysis of Natural Selection on the Human Haptoglobin Duplication

    OpenAIRE

    Rodriguez, Santiago; Williams, Dylan M; Guthrie, Philip AI; McArdle, Wendy L.; Smith, George Davey; Evans, David M.; Gaunt, Tom R.; Day, Ian NM

    2012-01-01

    Haptoglobin binds free haemoglobin that prevents oxidative damage produced by haemolysis. There is a copy number variant (CNV) in the haptoglobin gene (HP) consisting of two alleles, Hp1 (no duplication), and Hp2 (1.7kb duplication involving two exons). The spread of the Hp2 allele is believed to have taken place under selective pressures conferred by malaria resistance. However, molecular evidence is lacking and Hp did not emerge in genomewide SNPs surveys for evidence of selection. In Europ...

  20. Actin evolution in ciliates (Protist, Alveolata) is characterized by high diversity and three duplication events.

    Science.gov (United States)

    Yi, Zhenzhen; Huang, Lijuan; Yang, Ran; Lin, Xiaofeng; Song, Weibo

    2016-03-01

    Ciliates possess two distinct nuclear genomes and unique genomic features, including highly fragmented chromosomes and extensive chromosomal rearrangements. Recent transcriptomic surveys have revealed that ciliates have several multi-copy genes providing an ideal template to study gene family evolution. Nonetheless, this process remains little studied in ciliated protozoa and consequently, the evolutionary patterns that govern it are not well understood. In this study, we focused on obtaining fine-scale information relative to ciliate species divergence for the first time. A total of 230 actin gene sequences were derived from this study, among which 217 were from four closely related Pseudokeronopsis species and 13 from other hypotrichous ciliates. Our investigation shows that: (1) At least three duplication events occurred in ciliates: diversification of three actin genes (Actin I, II, III) happened after the divergence of ciliate classes but before that of subclasses. And several recent and genus-specific duplications were followed within Actin I (Sterkiella, Oxytricha, Uroleptus, etc.), Actin II (Sterkiella), respectively. (2) Within the genus Pseudokeronopsis, Actin I gene duplication events happened after P. carnea and P. erythrina diverged. In contrast, in the morphologically similar species P. flava and P. rubra, the duplication event preceded diversification of the two species. The Actin II gene duplication events preceded divergence of the genus Pseudokeronopsis. (3) Phylogenetic analyses revealed that actin is suitable for resolving ciliate classes, but may not be used to infer lower taxon relationships.

  1. Recurrent Chromosome 16p13.1 Duplications Are a Risk Factor for Aortic Dissections

    Science.gov (United States)

    McDonald, Merry-Lynn N.; Johnson, Ralph J.; Wang, Min; Regalado, Ellen S.; Russell, Ludivine; Cao, Jiu-Mei; Kwartler, Callie; Fraivillig, Kurt; Coselli, Joseph S.; Safi, Hazim J.; Estrera, Anthony L.; Leal, Suzanne M.; LeMaire, Scott A.; Belmont, John W.; Milewicz, Dianna M.

    2011-01-01

    Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD). In this study, we investigated the association of recurrent genomic copy number variants (CNVs) with thoracic aortic aneurysms and dissections (TAAD). By using SNP arrays to screen and comparative genomic hybridization microarrays to validate, we identified 16p13.1 duplications in 8 out of 765 patients of European descent with adult-onset TAAD compared with 4 of 4,569 controls matched for ethnicity (P = 5.0×10−5, OR = 12.2). The findings were replicated in an independent cohort of 467 patients of European descent with TAAD (P = 0.005, OR = 14.7). Patients with 16p13.1 duplications were more likely to harbor a second rare CNV (P = 0.012) and to present with aortic dissections (P = 0.010) than patients without duplications. Duplications of 16p13.1 were identified in 2 of 130 patients with familial TAAD, but the duplications did not segregate with TAAD in the families. MYH11, a gene known to predispose to TAAD, lies in the duplicated region of 16p13.1, and increased MYH11 expression was found in aortic tissues from TAAD patients with 16p13.1 duplications compared with control aortas. These data suggest chromosome 16p13.1 duplications confer a risk for TAAD in addition to the established risk for neuropsychiatric disorders. It also indicates that recurrent CNVs may predispose to disorders involving more than one organ system, an observation critical to the understanding of the role of recurrent CNVs in human disease and a finding that may be common to other recurrent CNVs involving multiple genes. PMID:21698135

  2. Recurrent chromosome 16p13.1 duplications are a risk factor for aortic dissections.

    Directory of Open Access Journals (Sweden)

    Shao-Qing Kuang

    2011-06-01

    Full Text Available Chromosomal deletions or reciprocal duplications of the 16p13.1 region have been implicated in a variety of neuropsychiatric disorders such as autism, schizophrenia, epilepsies, and attention-deficit hyperactivity disorder (ADHD. In this study, we investigated the association of recurrent genomic copy number variants (CNVs with thoracic aortic aneurysms and dissections (TAAD. By using SNP arrays to screen and comparative genomic hybridization microarrays to validate, we identified 16p13.1 duplications in 8 out of 765 patients of European descent with adult-onset TAAD compared with 4 of 4,569 controls matched for ethnicity (P = 5.0 × 10⁻⁵, OR = 12.2. The findings were replicated in an independent cohort of 467 patients of European descent with TAAD (P = 0.005, OR = 14.7. Patients with 16p13.1 duplications were more likely to harbor a second rare CNV (P = 0.012 and to present with aortic dissections (P = 0.010 than patients without duplications. Duplications of 16p13.1 were identified in 2 of 130 patients with familial TAAD, but the duplications did not segregate with TAAD in the families. MYH11, a gene known to predispose to TAAD, lies in the duplicated region of 16p13.1, and increased MYH11 expression was found in aortic tissues from TAAD patients with 16p13.1 duplications compared with control aortas. These data suggest chromosome 16p13.1 duplications confer a risk for TAAD in addition to the established risk for neuropsychiatric disorders. It also indicates that recurrent CNVs may predispose to disorders involving more than one organ system, an observation critical to the understanding of the role of recurrent CNVs in human disease and a finding that may be common to other recurrent CNVs involving multiple genes.

  3. Multiple independent origins of mitochondrial control region duplications in the order Psittaciformes

    Science.gov (United States)

    Schirtzinger, Erin E.; Tavares, Erika S.; Gonzales, Lauren A.; Eberhard, Jessica R.; Miyaki, Cristina Y.; Sanchez, Juan J.; Hernandez, Alexis; Müeller, Heinrich; Graves, Gary R.; Fleischer, Robert C.; Wright, Timothy F.

    2012-01-01

    Mitochondrial genomes are generally thought to be under selection for compactness, due to their small size, consistent gene content, and a lack of introns or intergenic spacers. As more animal mitochondrial genomes are fully sequenced, rearrangements and partial duplications are being identified with increasing frequency, particularly in birds (Class Aves). In this study, we investigate the evolutionary history of mitochondrial control region states within the avian order Psittaciformes (parrots and cockatoos). To this aim, we reconstructed a comprehensive multi-locus phylogeny of parrots, used PCR of three diagnostic fragments to classify the mitochondrial control region state as single or duplicated, and mapped these states onto the phylogeny. We further sequenced 44 selected species to validate these inferences of control region state. Ancestral state reconstruction using a range of weighting schemes identified six independent origins of mitochondrial control region duplications within Psittaciformes. Analysis of sequence data showed that varying levels of mitochondrial gene and tRNA homology and degradation were present within a given clade exhibiting duplications. Levels of divergence between control regions within an individual varied from 0–10.9% with the differences occurring mainly between 51 and 225 nucleotides 3′ of the goose hairpin in domain I. Further investigations into the fates of duplicated mitochondrial genes, the potential costs and benefits of having a second control region, and the complex relationship between evolutionary rates, selection, and time since duplication are needed to fully explain these patterns in the mitochondrial genome. PMID:22543055

  4. Duplication of CYP2D6 predicts high clearance of desipramine but high clearance does not predict duplication of CYP2D6

    DEFF Research Database (Denmark)

    Bergmann, T K; Bathum, L; Brøsen, Kim

    2001-01-01

    a duplicated allele. The question is whether gene duplication is a relatively rare cause (perhaps predictor) of very rapid metabolism or whether a low metabolic ratio is a poor predictor of this. METHODS: After measuring metabolic ratios anew, we selected six volunteers with duplication of CYP2D6 and metabolic...... ratios ranging from 0.07 to 0.17 and six volunteers without duplication with metabolic ratios ranging from 0.08 to 0.21. Each subject took 100 mg of desipramine. Blood and urine were collected for 48 h. RESULTS: The median total oral clearance of desipramine was 372 l/h and 196 l/h [median difference 108...... l/h (95.9% c.i., -304-598 l/h)] and the median partial clearance of desipramine by 2-hydroxylation was 155 l/h and 87 l/h [median difference 47 l/h (95.9% c.i., -124-141 l/h)] for the group with duplication and the group without duplication, respectively. CONCLUSION: The predictive value...

  5. Duplicated Ižnternal Juguler Vein

    Directory of Open Access Journals (Sweden)

    Ahmet Kirbas

    2014-03-01

    Full Text Available    Duplicated internal juguler vein (DIJV is a rare anomaly and reported incidence is 0.4 % in the literature. A 45-year-old female patient was referred to our hospital because of non pulsatile neck swelling. The magnetic resonance image (MRI showed left IJVs divided at the angles of the mandible running anterior to the common carotid artery until anterior mediastinal level. Clinicians should be aware of the rare possibility of duplicated IJVs in patients presenting with neck swelling. The development of imaging technics have revealed more cases of duplicated internal juguler vein.

  6. The fate of the duplicated androgen receptor in fishes: a late neofunctionalization event?

    Directory of Open Access Journals (Sweden)

    Haendler Bernard

    2008-12-01

    Full Text Available Abstract Background Based on the observation of an increased number of paralogous genes in teleost fishes compared with other vertebrates and on the conserved synteny between duplicated copies, it has been shown that a whole genome duplication (WGD occurred during the evolution of Actinopterygian fish. Comparative phylogenetic dating of this duplication event suggests that it occurred early on, specifically in teleosts. It has been proposed that this event might have facilitated the evolutionary radiation and the phenotypic diversification of the teleost fish, notably by allowing the sub- or neo-functionalization of many duplicated genes. Results In this paper, we studied in a wide range of Actinopterygians the duplication and fate of the androgen receptor (AR, NR3C4, a nuclear receptor known to play a key role in sex-determination in vertebrates. The pattern of AR gene duplication is consistent with an early WGD event: it has been duplicated into two genes AR-A and AR-B after the split of the Acipenseriformes from the lineage leading to teleost fish but before the divergence of Osteoglossiformes. Genomic and syntenic analyses in addition to lack of PCR amplification show that one of the duplicated copies, AR-B, was lost in several basal Clupeocephala such as Cypriniformes (including the model species zebrafish, Siluriformes, Characiformes and Salmoniformes. Interestingly, we also found that, in basal teleost fish (Osteoglossiformes and Anguilliformes, the two copies remain very similar, whereas, specifically in Percomorphs, one of the copies, AR-B, has accumulated substitutions in both the ligand binding domain (LBD and the DNA binding domain (DBD. Conclusion The comparison of the mutations present in these divergent AR-B with those known in human to be implicated in complete, partial or mild androgen insensitivity syndrome suggests that the existence of two distinct AR duplicates may be correlated to specific functional differences that may be

  7. Lateral gene transfer, rearrangement, reconciliation

    NARCIS (Netherlands)

    Patterson, M.D.; Szollosi, G.; Daubin, V.; Tannier, E.

    2013-01-01

    Background. Models of ancestral gene order reconstruction have progressively integrated different evolutionary patterns and processes such as unequal gene content, gene duplications, and implicitly sequence evolution via reconciled gene trees. These models have so far ignored lateral gene transfer,

  8. Patients with isolated oligo/hypodontia caused by RUNX2 duplication.

    Science.gov (United States)

    Molin, Arnaud; Lopez-Cazaux, Serena; Pichon, Olivier; Vincent, Marie; Isidor, Bertrand; Le Caignec, Cédric

    2015-06-01

    Loss-of-function mutations of RUNX2 are responsible for cleidocranial dysplasia, an autosomal dominant disorder characterized by delayed closure of cranial sutures, aplastic or hypoplastic clavicles, moderate short stature and supernumerary teeth. By contrast, an increased gene dosage is expected for duplication of the entire RUNX2 sequence and thus, a phenotype different from cleidocranial dysplasia. To date, two cousins with a duplication including the entire RUNX2 sequence in addition to MIR586, CLIC5 and the 5' half of SUPT3H have been reported. These patients presented with metopic synostosis and hypodontia. Here, we report on a family with an affected mother and three affected children. The four patients carried a 285 kb duplication identified by array comparative genomic hybridization. The duplication includes the entire sequence of RUNX2 and the 5' half of SUPT3H. We confirmed the duplication by real-time quantitative PCR in the four patients. Two children presented with the association of metopic craniosynostosis and oligo/hypodontia previously described, confirming the phenotype caused by RUNX2 duplication. Interestingly, the mother and one child had isolated hypodontia without craniosynostosis, broadening the phenotype observed in patients with such duplications.

  9. Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates.

    Science.gov (United States)

    Liu, Hai-Jing; Tang, Zhen-Xin; Han, Xue-Min; Yang, Zhi-Ling; Zhang, Fu-Min; Yang, Hai-Ling; Liu, Yan-Jing; Zeng, Qing-Yin

    2015-11-01

    Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.

  10. Nature and management of duplicate medication alerts

    NARCIS (Netherlands)

    Heringa, Mette; Floor, Annemieke; Meijer, Willemijn M.; De Smet, Peter A G M; Bouvy, Marcel L.|info:eu-repo/dai/nl/153182210

    2015-01-01

    OBJECTIVE: To investigate the nature of duplicate medication (DM) alerts, their management by community pharmacists, and potential characteristics of DM alerts that lead to interventions by pharmacists. METHODS: Observational study in 53 community pharmacies. Each pharmacist registered the nature

  11. Cep63 and cep152 cooperate to ensure centriole duplication.

    Directory of Open Access Journals (Sweden)

    Nicola J Brown

    Full Text Available Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152. In this study we show that Cep63 functions to ensure that centriole duplication occurs reliably in dividing mammalian cells. We show that the interaction between Cep63 and Cep152 can occur independently of centrosome localisation and that the two proteins are dependent on one another for centrosomal localisation. Further, both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. These observations describe the requirement for Cep63 in maintaining centriole number in dividing mammalian cells and further establish the order of events in centriole formation.

  12. Cep63 and cep152 cooperate to ensure centriole duplication.

    Science.gov (United States)

    Brown, Nicola J; Marjanović, Marko; Lüders, Jens; Stracker, Travis H; Costanzo, Vincenzo

    2013-01-01

    Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152. In this study we show that Cep63 functions to ensure that centriole duplication occurs reliably in dividing mammalian cells. We show that the interaction between Cep63 and Cep152 can occur independently of centrosome localisation and that the two proteins are dependent on one another for centrosomal localisation. Further, both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. These observations describe the requirement for Cep63 in maintaining centriole number in dividing mammalian cells and further establish the order of events in centriole formation.

  13. Primitive duplicate Hox clusters in the European eel's genome.

    Directory of Open Access Journals (Sweden)

    Christiaan V Henkel

    Full Text Available The enigmatic life cycle and elongated body of the European eel (Anguilla anguilla L., 1758 have long motivated scientific enquiry. Recently, eel research has gained in urgency, as the population has dwindled to the point of critical endangerment. We have assembled a draft genome in order to facilitate advances in all provinces of eel biology. Here, we use the genome to investigate the eel's complement of the Hox developmental transcription factors. We show that unlike any other teleost fish, the eel retains fully populated, duplicate Hox clusters, which originated at the teleost-specific genome duplication. Using mRNA-sequencing and in situ hybridizations, we demonstrate that all copies are expressed in early embryos. Theories of vertebrate evolution predict that the retention of functional, duplicate Hox genes can give rise to additional developmental complexity, which is not immediately apparent in the adult. However, the key morphological innovation elsewhere in the eel's life history coincides with the evolutionary origin of its Hox repertoire.

  14. Duplication: a Mechanism Producing Disassortative Mixing Networks in Biology

    Institute of Scientific and Technical Information of China (English)

    ZHAO Dan; LIU Zeng-Rong; WANG Jia-Zeng

    2007-01-01

    Assortative/disassortative mixing is an important topological property of a network. A network is called assortative mixing if the nodes in the network tend to connect to their connectivity peers, or disassortative mixing if nodes with low degrees are more likely to connect with high-degree nodes. We have known that biological networks such as protein-protein interaction networks (PPI), gene regulatory networks, and metabolic networks tend to be disassortative. On the other hand, in biological evolution, duplication and divergence are two fundamental processes. In order to make the relationship between the property of disassortative mixing and the two basic biological principles clear and to study the cause of the disassortative mixing property in biological networks, we present a random duplication model and an anti-preference duplication model. Our results show that disassortative mixing networks can be obtained by both kinds of models from uncorrelated initial networks.Moreover, with the growth of the network size, the disassortative mixing property becomes more obvious.

  15. Williams Syndrome and 15q Duplication: Coincidence versus Association.

    Science.gov (United States)

    Khokhar, Aditi; Agarwal, Swashti; Perez-Colon, Sheila

    2017-01-01

    Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN-specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.

  16. Characterization and evolution of conserved MicroRNA through duplication events in date palm (Phoenix dactylifera.

    Directory of Open Access Journals (Sweden)

    Yong Xiao

    Full Text Available MicroRNAs (miRNAs are important regulators of gene expression at the post-transcriptional level in a wide range of species. Highly conserved miRNAs regulate ancestral transcription factors common to all plants, and control important basic processes such as cell division and meristem function. We selected 21 conserved miRNA families to analyze the distribution and maintenance of miRNAs. Recently, the first genome sequence in Palmaceae was released: date palm (Phoenix dactylifera. We conducted a systematic miRNA analysis in date palm, computationally identifying and characterizing the distribution and duplication of conserved miRNAs in this species compared to other published plant genomes. A total of 81 miRNAs belonging to 18 miRNA families were identified in date palm. The majority of miRNAs in date palm and seven other well-studied plant species were located in intergenic regions and located 4 to 5 kb away from the nearest protein-coding genes. Sequence comparison showed that 67% of date palm miRNA members were present in duplicated segments, and that 135 pairs of miRNA-containing segments were duplicated in Arabidopsis, tomato, orange, rice, apple, poplar and soybean with a high similarity of non coding sequences between duplicated segments, indicating genomic duplication was a major force for expansion of conserved miRNAs. Duplicated miRNA pairs in date palm showed divergence in pre-miRNA sequence and in number of promoters, implying that these duplicated pairs may have undergone divergent evolution. Comparisons between date palm and the seven other plant species for the gain/loss of miR167 loci in an ancient segment shared between monocots and dicots suggested that these conserved miRNAs were highly influenced by and diverged as a result of genomic duplication events.

  17. 48 CFR 1331.205-70 - Duplication of effort.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Duplication of effort....205-70 Duplication of effort. The Department will not pay any costs for work that is duplicative of..., Duplication of Effort, in all cost-reimbursement, time and materials, and labor hour solicitations...

  18. 44 CFR 204.62 - Duplication and recovery of assistance.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Duplication and recovery of... Administration § 204.62 Duplication and recovery of assistance. (a) Duplication of benefits. We provide supplementary assistance under the Stafford Act, which generally may not duplicate benefits received by...

  19. Intragenic Duplication A Novel Mutational Mechanism in Hereditary Pancreatitis

    DEFF Research Database (Denmark)

    Joergensen, M. T.; Geisz, A.; Brusgaard, K.

    2011-01-01

    OBJECTIVES: In a hereditary pancreatitis family from Denmark, we identified a novel intragenic duplication of 9 nucleotides in exon-2 of the human cationic trypsinogen (PRSS1) gene (c.63_71dup) which at the amino-acid level resulted in the insertion of 3 amino acids within the activation peptide...... pancreatitis. The accelerated activation of p.K23_I24insIDK by cathepsin B is a unique biochemical property not found in any other pancreatitis-associated trypsinogen mutant. In contrast, the robust autoactivation of the novel mutant confirms the notion that increased autoactivation is a disease......-relevant mechanism in hereditary pancreatitis....

  20. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders

    Science.gov (United States)

    Isles, Anthony R.; Ingason, Andrés; Lowther, Chelsea; Gawlick, Micha; Stöber, Gerald; Potter, Harry; Georgieva, Lyudmila; Pizzo, Lucilla; Ozaki, Norio; Kushima, Itaru; Ikeda, Masashi; Iwata, Nakao; Levinson, Douglas F.; Gejman, Pablo V.; Shi, Jianxin; Sanders, Alan R.; Duan, Jubao; Sisodiya, Sanjay; Costain, Gregory; Degenhardt, Franziska; Giegling, Ina; Rujescu, Dan; Hreidarsson, Stefan J.; Saemundsen, Evald; Ahn, Joo Wook; Ogilvie, Caroline; Stefansson, Hreinn; Stefansson, Kari; O’Donovan, Michael C.; Owen, Michael J.; Bassett, Anne; Kirov, George

    2016-01-01

    Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally

  1. Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders.

    Directory of Open Access Journals (Sweden)

    Anthony R Isles

    2016-05-01

    Full Text Available Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS region have been associated with developmental delay (DD, autism spectrum disorder (ASD and schizophrenia (SZ. Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA, but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15 or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of

  2. Chromosome 17 centromere duplication and responsiveness to anthracycline-based neoadjuvant chemotherapy in breast cancer.

    Science.gov (United States)

    Tibau, Ariadna; López-Vilaró, Laura; Pérez-Olabarria, Maitane; Vázquez, Tania; Pons, Cristina; Gich, Ignasi; Alonso, Carmen; Ojeda, Belén; Ramón y Cajal, Teresa; Lerma, Enrique; Barnadas, Agustí; Escuin, Daniel

    2014-10-01

    Human epidermal growth factor receptor 2 (HER2) and topoisomerase II alpha (TOP2A) genes have been proposed as predictive biomarkers of sensitivity to anthracycline chemotherapy. Recently, chromosome 17 centromere enumeration probe (CEP17) duplication has also been associated with increased responsiveness to anthracyclines. However, reports are conflicting and none of these tumor markers can yet be considered a clinically reliable predictor of response to anthracyclines. We studied the association of TOP2A gene alterations, HER2 gene amplification, and CEP17 duplication with response to anthracycline-based neoadjuvant chemotherapy in 140 patients with operable or locally advanced breast cancer. HER2 was tested by fluorescence in situ hybridization and TOP2A and CEP17 by chromogenic in situ hybridization. Thirteen patients (9.3%) achieved pathologic complete response (pCR). HER2 amplification was present in 24 (17.5%) of the tumors. TOP2A amplification occurred in seven tumors (5.1%). CEP17 duplication was detected in 13 patients (9.5%). CEP17 duplication correlated with a higher rate of pCR [odds ratio (OR) 6.55, 95% confidence interval (95% CI) 1.25-34.29, P = .026], and analysis of TOP2A amplification showed a trend bordering on statistical significance (OR 6.97, 95% CI 0.96-50.12, P = .054). TOP2A amplification and CEP17 duplication combined were strongly associated with pCR (OR 6.71, 95% CI 1.66-27.01, P = .007). HER2 amplification did not correlate with pCR. Our results suggest that CEP17 duplication predicts pCR to primary anthracycline-based chemotherapy. CEP17 duplication, TOP2A amplifications, and HER2 amplifications were not associated with prognosis.

  3. Do Children Think that Duplicating the Body also Duplicates the Mind?

    Science.gov (United States)

    Hood, Bruce; Gjersoe, Nathalia L.; Bloom, Paul

    2012-01-01

    Philosophers use hypothetical duplication scenarios to explore intuitions about personal identity. Here we examined 5- to 6-year-olds' intuitions about the physical properties and memories of a live hamster that is apparently duplicated by a machine. In Study 1, children thought that more of the original's physical properties than episodic…

  4. Analyses of transcriptome sequences reveal multiple ancient large-scale duplication events in the ancestor of Sphagnopsida (Bryophyta).

    Science.gov (United States)

    Devos, Nicolas; Szövényi, Péter; Weston, David J; Rothfel