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More radical amino acid replacements in primates than in rodents: support for the evolutionary role of effective population size.

ABSTRACT: We examined the pattern of nucleotide substitution in 4933 conserved single-copy orthologous protein-coding genes of human, rhesus, mouse, and rat. Consistent with previous studies, the median ratio of the number of nonsynonymous substitutions per nonsynonymous site (d(N)) to the number of synonymous substitutions per synonymous site (d(S)) was significantly higher in the comparison between the two primates than in the comparison between the two rodents. This pattern was particularly strong in the case of genes expressed in the immune system, but also occurred in other genes, including a set of highly conserved genes involved in the regulation of transcription. Both synonymous and nonsynonymous differences occurred independently in the same codons in the primates and in the rodents to a greater extent than expected by chance, but the extent of the deviation from random expectation was much greater in the case of nonsynonymous differences. Parallel amino acid replacements occurred at the same sites in the primates and rodents far more frequently than expected by chance, but tended to involve very conservative amino acid changes. Divergent amino acid changes involved more chemically different amino acids than parallel changes, and divergent amino acid replacements between the primates were significantly more radical than those between the rodents. These results are most easily explained on the hypothesis that the evolution of these genes has been shaped largely by purifying selection, which has been less effective in primates than in rodents, presumably as a consequence of lower long-term effective population sizes in the former.

SUBMITTER: Hughes AL

PROVIDER: S-EPMC2706701 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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More radical amino acid replacements in primates than in rodents: support for the evolutionary role of effective population size.

Hughes Austin L AL Friedman Robert R

Gene 20090328 1-2

We examined the pattern of nucleotide substitution in 4933 conserved single-copy orthologous protein-coding genes of human, rhesus, mouse, and rat. Consistent with previous studies, the median ratio of the number of nonsynonymous substitutions per nonsynonymous site (d(N)) to the number of synonymous substitutions per synonymous site (d(S)) was significantly higher in the comparison between the two primates than in the comparison between the two rodents. This pattern was particularly strong in t ...[more]

PMID: 19332110

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Project description:As predicted by the nearly neutral model of evolution, numerous studies have shown that reduced N(e) accelerates the accumulation of slightly deleterious changes under genetic drift. While such studies have mostly focused on eukaryotes, bacteria also offer excellent models to explore the effects of N(e). Most notably, the genomes of host-dependent bacteria with small N(e) show signatures of genetic drift, including elevated K(a)/K(s). Here, I explore the utility of an alternative measure of selective constraint: the per-site rate of radical and conservative amino acid substitutions (D(r)/D(c)). I test the hypothesis that purifying selection against radical amino acid changes is less effective in two insect endosymbiont groups (Blochmannia of ants and Buchnera of aphids), compared to related gamma-Proteobacteria. Genome comparisons demonstrate a significant elevation in D(r)/D(c) in endosymbionts that affects the majority (66-79%) of shared orthologs examined. The elevation of D(r)/D(c) in endosymbionts affects all functional categories examined. Simulations indicate that D(r)/D(c) estimates are sensitive to codon frequencies and mutational parameters; however, estimation biases occur in the opposite direction as the patterns observed in genome comparisons, thereby making the inference of elevated D(r)/D(c) more conservative. Increased D(r)/D(c) and other signatures of genome degradation in endosymbionts are consistent with strong effects of genetic drift in their small populations, as well as linkage to selected sites in these asexual bacteria. While relaxed selection against radical substitutions may contribute, genome-wide processes such as genetic drift and linkage best explain the pervasive elevation in D(r)/D(c) across diverse functional categories that include basic cellular processes. Although the current study focuses on a few bacterial lineages, it suggests D(r)/D(c) is a useful gauge of selective constraint and may provide a valuable alternative to K(a)/K(s) when high sequence divergences preclude estimates of K(s). Broader application of D(r)/D(c) will benefit from approaches less prone to estimation biases.

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More radical amino acid replacements in primates than in rodents: support for the evolutionary role of effective population size.

Publications

More radical amino acid replacements in primates than in rodents: support for the evolutionary role of effective population size.

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