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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    ABSTRACT: Genetic factors may play an important role in species extinction but their actual effect remains poorly understood, particularly because of a strong and potentially masking effect expected from ecological traits. We investigated the role of genetics in mammal extinction taking both ecological and genetic factors into account. As a proxy for the role of genetics we used the ratio of the rates of nonsynonymous (amino acid changing) to synonymous (leaving the amino acid unchanged) nucleotide substitutions, Ka / Ks. Because most nonsynonymous substitutions are likely to be slightly deleterious and thus selected against, this ratio is a measure of the inefficiency of selection: if large (but less than 1), it implies a low efficiency of selection against nonsynonymous mutations. As a result, nonsynonymous mutations may accumulate and thus contribute to extinction. As a proxy for the role of ecology we used body mass W, with which most extinction-related ecological traits strongly correlate. As a measure of extinction risk we used species’ affiliation with the five levels of extinction threat according to the IUCN Red List of Threatened Species. We calculated Ka / Ks for mitochondrial protein-coding genes of 211 mammalian species, each of which was characterized by body mass and the level of threat. Using logistic regression analysis, we then constructed a set of logistic regression models of extinction risk on ln(Ka / Ks) and lnW. We found that Ka / Ks and body mass are responsible for a 38% and a 62% increase in extinction risk, respectively. Given that the standard error of these values is 13%, the contribution of genetic factors to extinction risk in mammals is estimated to be one-quarter to one-half of the total of ecological and genetic effects. We conclude that the effect of genetics on extinction is significant, though it is almost certainly smaller than the effect of ecological traits.
    Oikos 08/2015; 124(8):983-993. DOI:10.1111/oik.01734 · 3.44 Impact Factor
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    • "Additionally, phylogenetically independent contrasts (PIC) were performed to allow the use of parametric statistics on their dataset (Felsenstein, 1985). This is considered an incorrect application of PIC due to a number of factors, the main one being that dN/dS values are already a form of contrast calculated between two branches (Popadin et al., 2007). Of direct relevance to this study, Sun et al. (2011) explored our same question, regarding purifying selection based on energetics, by computing dN/dS ratios for migratory and non-migratory fish. "
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    ABSTRACT: Mitochondrial DNA is routinely used to answer a variety of biological questions; and there is growing evidence suggesting its accumulation of mutations is influenced by life history, effective population size and cellular energy requirements. This study examines the influence of phylogenetic patterns of metabolic activity on the evolution of mitochondrial DNA in fishes, given energy requirements associated with high performance versus sedentary life histories. It was determined that all 13 protein coding genes of the mitogenome experience a relaxation of purifying selection in sedentary fishes. This phenomenon was not detected in nuclear housekeeping genes, suggesting that it can be explained by the energy requirements of these groups, and possibly their effective population sizes. This study also examined the subunit binding sites of two subunits of cytochrome c oxidase (COXI and COXIII), and did not detect any differences in selection between these groups of fishes. These cytochrome c oxidase subunits interact with subunits that are encoded by the nuclear genome and it has been suggested that a unique form of coevolution occurs between these genomes in order to maintain function, and may have implications for speciation. Although this was not a main focus of this study, our preliminary results suggest that substitutions in subunit binding site regions are rare. The results from this study add to the growing literature on the complex relationship between mitochondrial DNA and the evolution of life histories across the tree of life. Copyright © 2015 Elsevier Inc. All rights reserved.
    Gene 07/2015; 572(1). DOI:10.1016/j.gene.2015.06.074 · 2.14 Impact Factor
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    • "We show that large-bodied primates (e.g., hominoids and cercopithecids) have lower average dN/dS rates than small-bodied tarsiers. This contrasts previous findings that in mitochondrial protein-coding genes, larger mammals, generally characterized by lower population sizes (Damuth 1981, 1991, White et al. 2007), have higher dN/dS rates relative to small mammals with high average N e (Popadin et al. 2007, 2013). Thus, the strength of random drift in tarsiers would have been largely shaped by colonization history rather than body size. "
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