Accumulation of sightly deleterious mutations in mitochondrial protein-coding genes of large versus small mammals

Departments of Genetics, Biological Faculty of M.V. Lomonosov Moscow State University, Vorobyevy Gory 1-12, Moscow 119992, Russia.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/2007; 104(33):13390-5. DOI: 10.1073/pnas.0701256104
Source: PubMed


After the effective size of a population, N(e), declines, some slightly deleterious amino acid replacements which were initially suppressed by purifying selection become effectively neutral and can reach fixation. Here we investigate this phenomenon for a set of all 13 mitochondrial protein-coding genes from 110 mammalian species. By using body mass as a proxy for N(e), we show that large mammals (i.e., those with low N(e)) as compared with small ones (in our sample these are, on average, 369.5 kg and 275 g, respectively) have a 43% higher rate of accumulation of nonsynonymous nucleotide substitutions relative to synonymous substitutions, and an 8-40% higher rate of accumulation of radical amino acid substitutions relative to conservative substitutions, depending on the type of amino acid classification. These higher rates result in a 6% greater amino acid dissimilarity between modern species and their most recent reconstructed ancestors in large versus small mammals. Because nonsynonymous substitutions are likely to be more harmful than synonymous substitutions, and radical amino acid substitutions are likely to be more harmful than conservative ones, our results suggest that large mammals experience less efficient purifying selection than small mammals. Furthermore, because in the course of mammalian evolution body size tends to increase and, consequently, N(e) tends to decline, evolution of mammals toward large body size may involve accumulation of slightly deleterious mutations in mitochondrial protein-coding genes, which may contribute to decline or extinction of large mammals.

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    • "Obviously, models 1 to 3 are truncated forms of the above equation. The correlation between lnW and ln(Ka/Ks) is relatively weak [albeit significant, r 2 = 0.10, P < 0.001; see also Popadin et al. (2007) and Welch et al. (2008) for a similar correlation between the ratio of nonsynonymous over synonymous substitution rates and body mass ], hence we do not expect collinearity to be a serious problem in models 3 and 4. "
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