evolgen

Selection on Mitochondrial Genomes

Given the amount of attention I devoted to the effect of selection on the relationship between mitochondrial DNA polymorphism and population size (see here, here, here, here, here, and here), it’s only appropriate that I link to this article by Meiklejohn, Montooth, and Rand on selection on mtDNA. Here’s the abstract:

Several recent studies have confirmed that mitochondrial DNA variation and evolution are not consistent with the neutral theory of molecular evolution and might be inappropriate for estimating effective population sizes. Evidence for the action of both positive and negative selection on mitochondrial genes has been put forward, and the complex genetics of mitochondrial DNA adds to the challenge of resolving this debate. The solution could lie in distinguishing genetic drift from ‘genetic draft’ and in dissecting the physiology of mitochondrial fitness.

This paper leans heavily on the Bazin et al paper from last year (that’s one of the “recent studies” that showed no relationship between mtDNA polymorphism and population size) and a follow-up paper which showed a relationship between mtDNA polymorphism and population size in mammals. But the authors also present some neat analysis in which they break the Bazin meta-data-set into sub-sets. As a recap, Bazin et al found more evidence for adaptive amino acid changes in invertebrates than vertebrates by comparing polymorphism and divergence in amino acid coding sequences from mtDNA. They used this pattern to argue that adaptive evolution of mtDNA sequences erases any relationship between mtDNA polymorphism and population size.

Many of the published mtDNA sequences come from cytochrome oxidase subunit (COX) genes and the cytochrome B (cytB) gene. Meiklejohn et al show that COX genes show more evidence for adaptive evolution in invertebrates than vertebrates, but cytB does not. The heterogeneity in adaptive evolution between mtDNA genes is not remarkable on its own, but it’s important because the vertebrate and invertebrate data sets have nearly inverse frequencies of sequences from these two genes (the vertebrate data set consists of mostly cytB, while the invertebrate data set is mostly COX). Therefore, some of the evidence for adaptive evolution could merely be the result of biased data.

But the most interesting aspect of this paper is how the authors turn Bazin et al’s model of adaptive evolution on its head by hypothesizing that the excess amino acid changes observed in invertebrates are the result of a higher rate of deleterious amino acid evolution in the invertebrates. Ironically, this hypothesis is based on the genetic draft model — the same model Bazin et al use when hypothesizing that adaptive fixations in invertebrates decouples mtDNA polymorphism and population size. Meiklejohn et al point out that Gillespie’s model of genetic draft predicts that there will be more deleterious fixations in larger populations because there are more linked loci fixed by adaptive evolution in large populations (the deleterious alleles are just along for the ride and get fixed as would any linked neutral variant). Because the test for adaptive evolution merely looks for an excess of amino acid changes, elevated rates of deleterious amino acid evolution and adaptive amino acid evolution will both leave the same signature.

This leads to a paradox: if deleterious amino acid changes are fixing due to draft, what are the loci under adaptive evolution that are dragging those deleterious alleles along for the ride? One possibility is that there are a few mtDNA mutations that are responsible for the sweeps, but Meiklejohn et al hypothesize that cytoplasmic parasites such as Wolbachia may be the cause. By manipulating the reproductive success of their hosts, these symbionts could affect the frequency of different mtDNA haplotypes in a population. Two taxa with high rates of symbiont infections, insects and round worms, also show elevated rates of mtDNA amino acid evolution.


Bazin E, Glemin S, Galtier N. 2006. Population size does not influence mitochondrial genetic diversity in animals. Science 312: 570-572. doi:10.1126/science.1122033

Gillespie JH. 2001. Is the population size of a species relevant to its evolution? Evolution 55: 2161-2169. doi:10.1111/j.0014-3820.2001.tb00732.x

Meiklejohn CD, Montooth KL, Rand DM. 2007. Positive and negative selection on the mitochondrial genome. Trends Genet. 23: 259-263. doi:10.1016/j.tig.2007.03.008

Mulligan CJ, Kitchen A, Miyamoto MM. 2006. Comment on “Population size does not influence mitochondrial genetic diversity in animals”. Science 314: 1390. doi:10.1126/science.1132585