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Nicolas Galtier - One of the best experts on this subject based on the ideXlab platform.
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codon usage bias in animals disentangling the effects of natural selection effective population size and gc biased Gene Conversion
Molecular Biology and Evolution, 2018Co-Authors: Nicolas Galtier, Camille Roux, Marjolaine Rousselle, Jonathan Romiguier, Emeric Figuet, Sylvain GleminAbstract:Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also Generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. In animals, the population Genetics of codon usage bias has only been studied in a handful of model organisms so far, and can be affected by confounding, nonadaptive processes such as GC-biased Gene Conversion and experimental artefacts. Using population transcriptomics data, we analyzed the relationship between codon usage, Gene expression, allele frequency distribution, and recombination rate in 30 nonmodel species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased Gene Conversion on codon usage by separately analyzing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons tend to be preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased Gene Conversion, which is widespread in animals and the main force determining the fate of AT↔GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.
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codon usage bias in animals disentangling the effects of natural selection effective population size and gc biased Gene Conversion
bioRxiv, 2017Co-Authors: Nicolas Galtier, Camille Roux, Marjolaine Rousselle, Jonathan Romiguier, Emeric Figuet, Sylvain Glemin, Nicolas Bierne, Laurent DuretAbstract:Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also Generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. Codon usage bias in animals has only been studied in a handful of model organisms so far, and can be affected by confounding, non-adaptive processes such as GC-biased Gene Conversion and experimental artefacts. Using population transcriptomics data we analysed the relationship between codon usage, Gene expression, allele frequency distribution and recombination rate in 31 non-model species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased Gene Conversion on codon usage by separately analysing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons are Generally preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased Gene Conversion, which is widespread in animals and the main force determining the fate of AT GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.
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biased Gene Conversion and the evolution of mammalian genomic landscapes
Annual Review of Genomics and Human Genetics, 2009Co-Authors: Laurent Duret, Nicolas GaltierAbstract:Recombination is typically thought of as a symmetrical process resulting in large-scale reciprocal Genetic exchanges between homologous chromosomes. Recombination events, however, are also accompanied by short-scale, unidirectional exchanges known as Gene Conversion in the neighborhood of the initiating double-strand break. A large body of evidence suggests that Gene Conversion is GC-biased in many eukaryotes, including mammals and human. AT/GC heterozygotes produce more GC- than AT-gametes, thus conferring a population advantage to GC-alleles in high-recombining regions. This apparently unimportant feature of our molecular machinery has major evolutionary consequences. Structurally, GC-biased Gene Conversion explains the spatial distribution of GC-content in mammalian genomes—the so-called isochore structure. Functionally, GC-biased Gene Conversion promotes the segregation and fixation of deleterious AT → GC mutations, thus increasing our genomic mutation load. Here we review the recent evidence for a GC...
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gc biased Gene Conversion promotes the fixation of deleterious amino acid changes in primates
Trends in Genetics, 2009Co-Authors: Nicolas Galtier, Laurent Duret, Sylvain Glemin, Vincent RanwezAbstract:GC-biased Gene Conversion (gBGC) is a recently discovered, recombination-associated segregation distortion, which influences GC-content dynamics in the mammalian genome. We scanned the primate proteome for examples of exon-specific, lineage-specific accelerated amino acid evolution. Here, we show that such episodes are frequently accompanied by an increase in GC-content, which extends to synonymous and intronic positions. This demonstrates that gBGC has substantially (negatively) impacted the evolutionary trajectory of human proteins by promoting the fixation of deleterious AT→GC mutations.
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adaptation or biased Gene Conversion extending the null hypothesis of molecular evolution
Trends in Genetics, 2007Co-Authors: Nicolas Galtier, Laurent DuretAbstract:The analysis of evolutionary rates is a popular approach to characterizing the effect of natural selection at the molecular level. Sequences contributing to species adaptation are expected to evolve faster than nonfunctional sequences because favourable mutations have a higher fixation probability than neutral ones. Such an accelerated rate of evolution might be due to factors other than natural selection, in particular GC-biased Gene Conversion. This is true of neutral sequences, but also of constrained sequences, which can be illustrated using the mouse Fxy Gene. Several criteria can discriminate between the natural selection and biased Gene Conversion models. These criteria suggest that the recently reported human accelerated regions are most likely the result of biased Gene Conversion. We argue that these regions, far from contributing to human adaptation, might represent the Achilles' heel of our genome.
Sylvain Glemin - One of the best experts on this subject based on the ideXlab platform.
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codon usage bias in animals disentangling the effects of natural selection effective population size and gc biased Gene Conversion
Molecular Biology and Evolution, 2018Co-Authors: Nicolas Galtier, Camille Roux, Marjolaine Rousselle, Jonathan Romiguier, Emeric Figuet, Sylvain GleminAbstract:Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also Generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. In animals, the population Genetics of codon usage bias has only been studied in a handful of model organisms so far, and can be affected by confounding, nonadaptive processes such as GC-biased Gene Conversion and experimental artefacts. Using population transcriptomics data, we analyzed the relationship between codon usage, Gene expression, allele frequency distribution, and recombination rate in 30 nonmodel species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased Gene Conversion on codon usage by separately analyzing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons tend to be preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased Gene Conversion, which is widespread in animals and the main force determining the fate of AT↔GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.
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codon usage bias in animals disentangling the effects of natural selection effective population size and gc biased Gene Conversion
bioRxiv, 2017Co-Authors: Nicolas Galtier, Camille Roux, Marjolaine Rousselle, Jonathan Romiguier, Emeric Figuet, Sylvain Glemin, Nicolas Bierne, Laurent DuretAbstract:Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also Generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. Codon usage bias in animals has only been studied in a handful of model organisms so far, and can be affected by confounding, non-adaptive processes such as GC-biased Gene Conversion and experimental artefacts. Using population transcriptomics data we analysed the relationship between codon usage, Gene expression, allele frequency distribution and recombination rate in 31 non-model species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased Gene Conversion on codon usage by separately analysing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons are Generally preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased Gene Conversion, which is widespread in animals and the main force determining the fate of AT GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.
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gc biased Gene Conversion promotes the fixation of deleterious amino acid changes in primates
Trends in Genetics, 2009Co-Authors: Nicolas Galtier, Laurent Duret, Sylvain Glemin, Vincent RanwezAbstract:GC-biased Gene Conversion (gBGC) is a recently discovered, recombination-associated segregation distortion, which influences GC-content dynamics in the mammalian genome. We scanned the primate proteome for examples of exon-specific, lineage-specific accelerated amino acid evolution. Here, we show that such episodes are frequently accompanied by an increase in GC-content, which extends to synonymous and intronic positions. This demonstrates that gBGC has substantially (negatively) impacted the evolutionary trajectory of human proteins by promoting the fixation of deleterious AT→GC mutations.
Laurent Duret - One of the best experts on this subject based on the ideXlab platform.
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gc biased Gene Conversion conceals the prediction of the nearly neutral theory in avian genomes
Genome Biology, 2019Co-Authors: Paulina Bolivar, Laurent Duret, Laurent Gueguen, Hans Ellegren, Carina F MugalAbstract:The nearly neutral theory of molecular evolution predicts that the efficacy of natural selection increases with the effective population size. This prediction has been verified by independent observations in diverse taxa, which show that life-history traits are strongly correlated with measures of the efficacy of selection, such as the dN/dS ratio. Surprisingly, avian taxa are an exception to this theory because correlations between life-history traits and dN/dS are apparently absent. Here we explore the role of GC-biased Gene Conversion on estimates of substitution rates as a potential driver of these unexpected observations. We analyze the relationship between dN/dS estimated from alignments of 47 avian genomes and several proxies for effective population size. To distinguish the impact of GC-biased Gene Conversion from selection, we use an approach that accounts for non-stationary base composition and estimate dN/dS separately for changes affected or unaffected by GC-biased Gene Conversion. This analysis shows that the impact of GC-biased Gene Conversion on substitution rates can explain the lack of correlations between life-history traits and dN/dS. Strong correlations between life-history traits and dN/dS are recovered after accounting for GC-biased Gene Conversion. The correlations are robust to variation in base composition and genomic location. Our study shows that Gene sequence evolution across a wide range of avian lineages meets the prediction of the nearly neutral theory, the efficacy of selection increases with effective population size. Moreover, our study illustrates that accounting for GC-biased Gene Conversion is important to correctly estimate the strength of selection.
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codon usage bias in animals disentangling the effects of natural selection effective population size and gc biased Gene Conversion
bioRxiv, 2017Co-Authors: Nicolas Galtier, Camille Roux, Marjolaine Rousselle, Jonathan Romiguier, Emeric Figuet, Sylvain Glemin, Nicolas Bierne, Laurent DuretAbstract:Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also Generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. Codon usage bias in animals has only been studied in a handful of model organisms so far, and can be affected by confounding, non-adaptive processes such as GC-biased Gene Conversion and experimental artefacts. Using population transcriptomics data we analysed the relationship between codon usage, Gene expression, allele frequency distribution and recombination rate in 31 non-model species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased Gene Conversion on codon usage by separately analysing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons are Generally preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased Gene Conversion, which is widespread in animals and the main force determining the fate of AT GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.
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biased Gene Conversion and the evolution of mammalian genomic landscapes
Annual Review of Genomics and Human Genetics, 2009Co-Authors: Laurent Duret, Nicolas GaltierAbstract:Recombination is typically thought of as a symmetrical process resulting in large-scale reciprocal Genetic exchanges between homologous chromosomes. Recombination events, however, are also accompanied by short-scale, unidirectional exchanges known as Gene Conversion in the neighborhood of the initiating double-strand break. A large body of evidence suggests that Gene Conversion is GC-biased in many eukaryotes, including mammals and human. AT/GC heterozygotes produce more GC- than AT-gametes, thus conferring a population advantage to GC-alleles in high-recombining regions. This apparently unimportant feature of our molecular machinery has major evolutionary consequences. Structurally, GC-biased Gene Conversion explains the spatial distribution of GC-content in mammalian genomes—the so-called isochore structure. Functionally, GC-biased Gene Conversion promotes the segregation and fixation of deleterious AT → GC mutations, thus increasing our genomic mutation load. Here we review the recent evidence for a GC...
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gc biased Gene Conversion promotes the fixation of deleterious amino acid changes in primates
Trends in Genetics, 2009Co-Authors: Nicolas Galtier, Laurent Duret, Sylvain Glemin, Vincent RanwezAbstract:GC-biased Gene Conversion (gBGC) is a recently discovered, recombination-associated segregation distortion, which influences GC-content dynamics in the mammalian genome. We scanned the primate proteome for examples of exon-specific, lineage-specific accelerated amino acid evolution. Here, we show that such episodes are frequently accompanied by an increase in GC-content, which extends to synonymous and intronic positions. This demonstrates that gBGC has substantially (negatively) impacted the evolutionary trajectory of human proteins by promoting the fixation of deleterious AT→GC mutations.
-
adaptation or biased Gene Conversion extending the null hypothesis of molecular evolution
Trends in Genetics, 2007Co-Authors: Nicolas Galtier, Laurent DuretAbstract:The analysis of evolutionary rates is a popular approach to characterizing the effect of natural selection at the molecular level. Sequences contributing to species adaptation are expected to evolve faster than nonfunctional sequences because favourable mutations have a higher fixation probability than neutral ones. Such an accelerated rate of evolution might be due to factors other than natural selection, in particular GC-biased Gene Conversion. This is true of neutral sequences, but also of constrained sequences, which can be illustrated using the mouse Fxy Gene. Several criteria can discriminate between the natural selection and biased Gene Conversion models. These criteria suggest that the recently reported human accelerated regions are most likely the result of biased Gene Conversion. We argue that these regions, far from contributing to human adaptation, might represent the Achilles' heel of our genome.
Eric Wagner - One of the best experts on this subject based on the ideXlab platform.
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de novo Gene Conversion in the rca Gene cluster 1q32 causes mutations in complement factor h associated with atypical hemolytic uremic syndrome
Human Mutation, 2006Co-Authors: Stefan Heinen, Pilar Sanchezcorral, Michael S Jackson, Lisa Strain, Judith Goodship, Elizabeth J Kemp, Christine Skerka, Sakari T Jokiranta, Kevin E C Meyers, Eric WagnerAbstract:Many of the complement regulatory Genes within the RCA cluster (1q32) have arisen through genomic duplication and the resulting high degree of sequence identity is likely to predispose to Gene Conversion events. The highest degree of identity is between the Genes for factor H (CFH) and five factor H-related proteins--CFHL1, CFHL2, CFHL3, CFHL4, and CFHL5. CFH mutations are associated with atypical hemolytic uremic syndrome (aHUS). In the Newcastle cohort of 157 aHUS patients we have identified CFH mutations in 25 families or individuals. Eleven of these 25 independent mutations are either c.3226C>G,Q1076E; c.3572C>T,S1191L; c.3590T>C,V1197A or combined c.3572C>T,S1191L/c.3590T>C,V1197A. Sequence analysis shows that all four of these changes could have arisen as a result of Gene Conversion between CFH and CFHL1. Analysis of parental samples in two patients with S1191L/V1197A has shown that the changes are de novo thus providing conclusive evidence that Gene Conversion is the mutational mechanism in these two cases. To confirm that S1191L and V1197A are disease predisposing we examined their functional significance in three ways - analysis of the C3b/C3d binding characteristics of recombinant mutant S1191L/V1197A protein, heparin affinity chromatography and haemolytic assays of serum samples from aHUS patients carrying these changes. The results showed that these changes resulted in impaired C3b binding and a defective capacity to control complement activation on cellular surfaces. We, therefore, provide conclusive evidence that Gene Conversion is responsible for functionally significant CFH mutations in aHUS.
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de novo Gene Conversion in the rca Gene cluster 1q32 causes mutations in complement factor h associated with atypical hemolytic uremic syndrome
Human Mutation, 2006Co-Authors: Stefan Heinen, Pilar Sanchezcorral, Michael S Jackson, Lisa Strain, Elizabeth J Kemp, Christine Skerka, Sakari T Jokiranta, Kevin E C Meyers, Judith A Goodship, Eric WagnerAbstract:Many of the complement regulatory Genes within the RCA cluster (1q32) have arisen through genomic duplication and the resulting high degree of sequence identity is likely to predispose to Gene Conversion events. The highest degree of identity is between the Genes for factor H (CFH) and five factor H-related proteins – CFHL1, CFHL2, CFHL3, CFHL4, and CFHL5. CFH mutations are associated with atypical hemolytic uremic syndrome (aHUS). In the Newcastle cohort of 157 aHUS patients we have identified CFH mutations in 25 families or individuals. Eleven of these 25 independent mutations are either c.3226C>G,Q1076E; c.3572C>T,S1191L; c.3590T>C,V1197A or combined c.3572C>T,S1191L/c.3590T>C,V1197A. Sequence analysis shows that all four of these changes could have arisen as a result of Gene Conversion between CFH and CFHL1. Analysis of parental samples in two patients with S1191L/V1197A has shown that the changes are de novo thus providing conclusive evidence that Gene Conversion is the mutational mechanism in these two cases. To confirm that S1191L and V1197A are disease predisposing we examined their functional significance in three ways – analysis of the C3b/C3d binding characteristics of recombinant mutant S1191L/V1197A protein, heparin affinity chromatography and haemolytic assays of serum samples from aHUS patients carrying these changes. The results showed that these changes resulted in impaired C3b binding and a defective capacity to control complement activation on cellular surfaces. We, therefore, provide conclusive evidence that Gene Conversion is responsible for functionally significant CFH mutations in aHUS. © 2006 Wiley-Liss, Inc.
Camille Roux - One of the best experts on this subject based on the ideXlab platform.
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codon usage bias in animals disentangling the effects of natural selection effective population size and gc biased Gene Conversion
Molecular Biology and Evolution, 2018Co-Authors: Nicolas Galtier, Camille Roux, Marjolaine Rousselle, Jonathan Romiguier, Emeric Figuet, Sylvain GleminAbstract:Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also Generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. In animals, the population Genetics of codon usage bias has only been studied in a handful of model organisms so far, and can be affected by confounding, nonadaptive processes such as GC-biased Gene Conversion and experimental artefacts. Using population transcriptomics data, we analyzed the relationship between codon usage, Gene expression, allele frequency distribution, and recombination rate in 30 nonmodel species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased Gene Conversion on codon usage by separately analyzing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons tend to be preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased Gene Conversion, which is widespread in animals and the main force determining the fate of AT↔GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.
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codon usage bias in animals disentangling the effects of natural selection effective population size and gc biased Gene Conversion
bioRxiv, 2017Co-Authors: Nicolas Galtier, Camille Roux, Marjolaine Rousselle, Jonathan Romiguier, Emeric Figuet, Sylvain Glemin, Nicolas Bierne, Laurent DuretAbstract:Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also Generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. Codon usage bias in animals has only been studied in a handful of model organisms so far, and can be affected by confounding, non-adaptive processes such as GC-biased Gene Conversion and experimental artefacts. Using population transcriptomics data we analysed the relationship between codon usage, Gene expression, allele frequency distribution and recombination rate in 31 non-model species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased Gene Conversion on codon usage by separately analysing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons are Generally preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased Gene Conversion, which is widespread in animals and the main force determining the fate of AT GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.