Prediction of harmful variants on mitochondrial genes: Test of habitat‐dependent and demographic effects in a euryhaline fish

Abstract

Both effective population size and life history may influence the efficacy of purifying selection, but it remains unclear if the environment affects the accumulation of weakly deleterious nonsynonymous polymorphisms. We hypothesize that the reduced energetic cost of osmoregulation in brackish water habitat may cause relaxation of selective constraints at mitochondrial oxidative phosphorylation (OXPHOS) genes. To test this hypothesis, we analyzed 57 complete mitochondrial genomes of Pungitius pungitius collected from brackish and freshwater habitats. Based on inter‐ and intraspecific comparisons, we estimated that 84% and 68% of the nonsynonymous polymorphisms in the freshwater and brackish water populations, respectively, are weakly or moderately deleterious. Using in silico prediction tools (MutPred, SNAP2), we subsequently identified nonsynonymous polymorphisms with potentially harmful effect. Both prediction methods indicated that the functional effects of the fixed nonsynonymous substitutions between nine‐ and three‐spined stickleback were weaker than for polymorphisms within species, indicating that harmful nonsynonymous polymorphisms within populations rarely become fixed between species. No significant differences in mean estimated functional effects were identified between freshwater and brackish water nine‐spined stickleback to support the hypothesis that reduced osmoregulatory energy demand in the brackish water environment reduces the strength of purifying selection at OXPHOS genes. Instead, elevated frequency of nonsynonymous polymorphisms in the freshwater environment (P n /P s = 0.549 vs. 0.283; Fisher's exact test p = .032) suggested that purifying selection is less efficient in small freshwater populations. This study shows the utility of in silico functional prediction tools in population genetic and evolutionary research in a nonmammalian vertebrate and demonstrates that mitochondrial energy production genes represent a promising system to characterize the demographic, life history and potential habitat‐dependent effects of segregating amino acid variants.

Impact of supplementation on deleterious mutation distribution in an exploited salmonid

“…Our empirical GBS data on a nonmodel species highlights the fact that the prediction of the functional effect of amino acid change actually depends on the direction of amino acid substitution as suggested by Vasemägi et al. (). For several categories, one direction exhibits mainly “neutral” nonsynonymous mutations, whereas the other direction presents mainly putative deleterious mutations.…”

Extreme mito-nuclear discordance in a peninsular lizard: the role of drift, selection, and climate

“…Evolutionary forces such as drift and natural selection do not generally act in isolation, and their effect on the genome is largely dependent on population size (Ohta 1992; Tong et al 2017). Population size reduction due to drift following isolation can also lead to an increase in frequency of effectively neutral non-synonymous variants (Popadin et al 2007; Pavlova et al 2017; Vasemägi et al 2017).…”

Unlocking the genome of perch – From genes to ecology and back again

“…Thus, any future studies aiming to resolve phylogenetic relationships and colonisation history in perch should focus on an analysis of much longer mitochondrial fragments to accurately infer the evolutionary relationships between haplotypes and populations. Furthermore, considering the functional importance of mitochondrial genes, there is an increasing interest in understanding both the neutral and selective processes that shape mtDNA variation (Consuegra et al, 2015; Vasemägi et al, 2017) and its link to adaptation to warmer environments (Pichaud et al, 2020) as well as potential coadaptation of mitochondrial and nuclear genes (Hill, 2019).…”