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

Abstract

After the effective size of a population, Ne, 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 Ne) 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.body mass ͉ effective population size ͉ substitution rates ͉ purifying selection ͉ body size-dependent extinction N atural selection is more efficient in large populations. In a population of effective size N e , mutations with selection coefficient s such that ͉s͉ Ͻ 1/N e are effectively neutral, in the sense that their dynamics are affected mostly by random drift (1, 2). Effectively neutral nucleotide substitutions, both slightly deleterious and slightly beneficial, play a major role in evolution at the molecular level (3). Provided that the distribution of selection coefficient is independent of N e , the fraction of mutations which are effectively neutral must be higher in populations with smaller N e . Because selection is mostly purifying, in species with low N e a larger fraction of slightly deleterious mutations can reach fixation.Purifying selection affects nonsynonymous substitutions much stronger than synonymous substitutions (4-6). Indeed, when the ratio of the rate of nonsynonymous (amino acid changing) substitutions over the rate of synonymous (silent) substitutions, K a /K s , is Ͻ1, it is indicative of purifying selection on nonsynonymous substitutions and reflects its strength: the closer the K a /K s to 1, the weaker is the purifying selection (3). Another measure of the strength of purifying selection is the ratio of the rate of radical (presumably more harmful) over the rate of conservative (less harmful) amino acid sub...

Adaptive evolution of energy metabolism genes and the origin of flight in bats

“…First, we used the one-ratio model (M 0 ), a very strict model that allows only a single K a /Ks ratio for all branches. The K a /Ks ratios that we obtained for all 13 individual mitochondrial genes are significantly less than 1, providing good support for the expected presence of negative selection acting on all mitochondrial genes, showing that strong purifying selection plays a central role in the evolution of mtDNA to keep its important functions in energy metabolism (22)(23)(24)(25)(26). Purifying selection, by itself, cannot generate "good" genes as it only maintains a gene's function.…”

Mitochondrially encoded methionine is inversely related to longevity in mammals

“…Therefore, methionine addition, rather than methionine loss, is probably the mechanism determining the current differences in methionine usage among mammals with different longevities. Because the literature suggests that long-lived mammals exhibit a less effective purifying selection (Popadin et al, 2007), it is unlikely that long-lived mammals avoid methionine addition events through a more effective purifying selection. Therefore, rather than long-lived mammals losing methionine, we think short-lived mammals gain methionine.…”

Genetic aspects of mitochondrial genome evolution

“…The strength of this effect depends on population size. Indeed, an increased number of amino acid substitutions has been reported from large mammals, which tend to have small populations (Popadin et al, 2007). Overall, however, the function of mitochondrial proteins is preserved by very strong selection, reviewed in detail in (Castellana et al, 2011).…”