GC-Biased Segregation of Noncoding Polymorphisms in Drosophila

Galtier, Nicolas; Bazin, Éric; Bierne, Nicolas

doi:10.1534/genetics.105.046524

Cited by 59 publications

(60 citation statements)

References 36 publications

(34 reference statements)

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“…Evolution of base composition: The action of nonselective forces, such as biased gene conversion in favor of GC over AT (Galtier et al 2006), or changes in mutational biases may cause a departure from neutrality in the nucleotide composition of the chromosomes. These could be confounded with selection on codon usage, since most optimal codons in D. pseudoobscura end in G or C (Akashi and Schaeffer 1997).…”

Section: Resultsmentioning

confidence: 99%

Evolution of Amino-Acid Sequences and Codon Usage on the Drosophila miranda Neo-Sex Chromosomes

Bartolomé

Charlesworth

2006

Genetics

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We have studied patterns of DNA sequence variation and evolution for 22 genes located on the neo-X and neo-Y chromosomes of Drosophila miranda. As found previously, nucleotide site diversity is greatly reduced on the neo-Y chromosome, with a severely distorted frequency spectrum. There is also an accelerated rate of amino-acid sequence evolution on the neo-Y chromosome. Comparisons of nonsynonymous and silent variation and divergence suggest that amino-acid sequences on the neo-X chromosome are subject to purifying selection, whereas this is much weaker on the neo-Y. The same applies to synonymous variants affecting codon usage. There is also an indication of a recent relaxation of selection on synonymous mutations for genes on other chromosomes. Genes that are weakly expressed on the neo-Y chromosome appear to have a faster rate of accumulation of both nonsynonymous and unpreferred synonymous mutations than genes with high levels of expression, although the rate of accumulation when both types of mutation are pooled is higher for the neo-Y chromosome than for the neo-X chromosome even for highly expressed genes.

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Section: Resultsmentioning

confidence: 99%

Evolution of Amino-Acid Sequences and Codon Usage on the Drosophila miranda Neo-Sex Chromosomes

Bartolomé

Charlesworth

2006

Genetics

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“…Third, we have assumed that synonymous mutations are neutral, but there is evidence of selection in humans (Iida and Akashi 2000) and other species (Duret 2002;Pond and Muse 2005); although it is clear that selection has acted upon synonymous mutations in the past in D. melanogaster, the evidence of selection currently acting is contradictory (Akashi 1996;McVean and Vieira 2001;Zeng and Charlesworth 2010) and biased gene conversion may be acting (Galtier et al 2006;Zeng and Charlesworth 2010). Most of the other species we have analyzed have not been investigated in any detail.…”

Section: Discussionmentioning

confidence: 99%

“…However, as we have noted earlier, the estimate assuming free recombination should give an upper estimate on the amount of variation, because under this method all variation in the diversity is assumed to arise from sampling error and variation in the mutation rate and N e . In reality, some of the variation between genes is a consequence of variation in the length of the genealogy in genes with little or no recombination.Second, we have used the divergence between species as an estimate of the mutation rate, but if the mutation rate at a locus changes through time, for which there is evidence (Aguileta et al 2006;Hodgkinson and Eyre-Walker 2011), then we will tend to overestimate the variation in N e : this is most easily seen by assuming there is variation in the mutation rate, but no variation in N e ; if the mutation rate has changed through time, then the divergence will not be a perfect measure of the recent mutation rate and there will appear to be variation in N e .Third, we have assumed that synonymous mutations are neutral, but there is evidence of selection in humans (Iida and Akashi 2000) and other species (Duret 2002;Pond and Muse 2005); although it is clear that selection has acted upon synonymous mutations in the past in D. melanogaster, the evidence of selection currently acting is contradictory (Akashi 1996;McVean and Vieira 2001;Zeng and Charlesworth 2010) and biased gene conversion may be acting (Galtier et al 2006;Zeng and Charlesworth 2010). Most of the other species we have analyzed have not been investigated in any detail.…”

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confidence: 99%

Quantifying the Variation in the Effective Population Size Within a Genome

2011

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The effective population size (N e ) is one of the most fundamental parameters in population genetics. It is thought to vary across the genome as a consequence of differences in the rate of recombination and the density of selected sites due to the processes of genetic hitchhiking and background selection. Although it is known that there is intragenomic variation in the effective population size in some species, it is not known whether this is widespread or how much variation in the effective population size there is. Here, we test whether the effective population size varies across the genome, between protein-coding genes, in 10 eukaryotic species by considering whether there is significant variation in neutral diversity, taking into account differences in the mutation rate between loci by using the divergence between species. In most species we find significant evidence of variation. We investigate whether the variation in N e is correlated to recombination rate and the density of selected sites in four species, for which these data are available. We find that N e is positively correlated to recombination rate in one species, Drosophila melanogaster, and negatively correlated to a measure of the density of selected sites in two others, humans and Arabidopsis thaliana. However, much of the variation remains unexplained. We use a hierarchical Bayesian analysis to quantify the amount of variation in the effective population size and show that it is quite modest in all species-most genes have an N e that is within a few fold of all other genes. Nonetheless we show that this modest variation in N e is sufficient to cause significant differences in the efficiency of natural selection across the genome, by demonstrating that the ratio of the number of nonsynonymous to synonymous polymorphisms is significantly correlated to synonymous diversity and estimates of N e , even taking into account the obvious nonindependence between these measures.T HE effective population size (N e ) is one of the most fundamental quantities in population genetics, evolutionary biology, and molecular ecology, since it determines the effectiveness of natural selection and the level of neutral genetic diversity that a population contains (Charlesworth 2009). Populations and regions of the genome with small N e tend to have low levels of genetic diversity, to be susceptible to the accumulation of deleterious mutations through genetic drift, and to have potentially low rates of adaptive evolution (Charlesworth 2009).The effective population size is expected to vary across the genome as a consequence of genetic hitchhiking (Smith and Haigh 1974) and background selection (Charlesworth et al. 1993). The action of both positive and negative natural selection, particularly in regions of the genome with low rates of recombination, is expected to reduce the effective population size leading to lower levels of genetic diversity and reduced effectiveness of selection. Hence variation in the rate of recombination and the density of selected sit...

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“…Predictions for changes in biased gene conversion (BGC) depend on the relative contributions of selection and BGC to codon bias and are less clear. However, changes in BGC would presumably affect intron base composition (Galtier et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Molecular Evolution in the Drosophila melanogaster Species Subgroup: Frequent Parameter Fluctuations on the Timescale of Molecular Divergence

Akashi

Piao

et al. 2006

Genetics

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Although mutation, genetic drift, and natural selection are well established as determinants of genome evolution, the importance (frequency and magnitude) of parameter fluctuations in molecular evolution is less understood. DNA sequence comparisons among closely related species allow specific substitutions to be assigned to lineages on a phylogenetic tree. In this study, we compare patterns of codon usage and protein evolution in 22 genes (.11,000 codons) among Drosophila melanogaster and five relatives within the D. melanogaster subgroup. We assign changes to eight lineages using a maximum-likelihood approach to infer ancestral states. Uncertainty in ancestral reconstructions is taken into account, at least to some extent, by weighting reconstructions by their posterior probabilities. Four of the eight lineages show potentially genomewide departures from equilibrium synonymous codon usage; three are decreasing and one is increasing in major codon usage. Several of these departures are consistent with lineage-specific changes in selection intensity (selection coefficients scaled to effective population size) at silent sites. Intron base composition and rates and patterns of protein evolution are also heterogeneous among these lineages. The magnitude of forces governing silent, intron, and protein evolution appears to have varied frequently, and in a lineage-specific manner, within the D. melanogaster subgroup. U NDERSTANDING the forces governing the origins and evolutionary fates of DNA mutations is central to the study of molecular evolution. A great deal of attention has been focused on determining the relative contributions of genetic drift and natural selection to patterns of divergence among genomes (reviewed in Ohta 2002). However, the magnitude, timescale, and genomic breadth of fluctuations in molecular evolutionary forces remain to be studied systematically. Such knowledge is critical for modeling the causes of molecular evolution and is necessary for designing tests of adaptive and deleterious evolution and methods for phylogenetic inference and ancestral state reconstruction.Determinants of molecular evolution include mutation rates and patterns, effective population sizes, rates of recombination and biased gene conversion, and the fitness effects of mutations. Strict constancy of all these factors is implausible. However, the timescale of parameter fluctuations determines their relevance to molecular evolution; variability in evolutionary forces cause heterogeneous substitution patterns if parameters changes occur on a similar timescale as molecular evolution (Gillespie 1993(Gillespie , 1994 Cutler 2000a,b). Although theoretical concerns suggest that appropriately scaled parameter fluctuations should not be common, numerous studies have invoked nonstationarity to explain variable rates of protein evolution at particular loci or in specific lineages. These include fluctuations in neutral mutation rates (Fitch and Markowitz 1970;Fitch 1971;Takahata 1987), effective population sizes (e.g., Oht...

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GC-Biased Segregation of Noncoding Polymorphisms in Drosophila

Cited by 59 publications

References 36 publications

Evolution of Amino-Acid Sequences and Codon Usage on the Drosophila miranda Neo-Sex Chromosomes

Evolution of Amino-Acid Sequences and Codon Usage on the Drosophila miranda Neo-Sex Chromosomes

Quantifying the Variation in the Effective Population Size Within a Genome

Molecular Evolution in the Drosophila melanogaster Species Subgroup: Frequent Parameter Fluctuations on the Timescale of Molecular Divergence

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