A mitochondrial mutational signature of temperature in ectothermic and endothermic vertebrates

Abstract

ABSTRACTMutational spectrum of the mitochondrial genome (mtDNA) fluctuates between species, however, factors responsible for this variation are mainly unknown. Recently, we demonstrated that the mammalian mtDNA mutational spectrum is associated with age-related oxidative damage by means of A>G substitutions on a heavy chain (hereafter Ah>Gh). Here we extend this logic hypothesizing that oxidative damage can also depend on a species-specific level of aerobic metabolism. Using body temperature of endotherms and the environmental temperature of ectotherms as a proxy for their levels of aerobic metabolism, we reconstructed and analyzed 1350 species-specific mtDNA mutational spectra of vertebrate species. First, within ray-finned fishes, we observed that temperature is associated with increased asymmetry of Ah>Gh substitution, estimated as a ratio Ah>Gh/Th>Ch. Second, comparing within-species geographically distinct clades of widely distributed European anchovy, we observed similarly increased Ah>Gh/Th>Ch in the tropical clade. Third, analysing nucleotide composition in the most neutral synonymous sites of fishes, we demonstrated that warm-versus cold-water fishes are expectedly more AC poor and GT rich. Fourth, within mammals we observed an increased Ah>Gh/Th>Ch in warmer species as compared to colder ones (hybernators, daily torpors, naked mole rat, etc.) Fifth, comparing mtDNA mutational spectra between five classes of vertebrates, we observed an increased Ah>Gh/Th>Ch in warm- (mammals and birds) versus cold- (actinopterygii, amphibia, reptilia) blooded classes. Altogether, we conclude that temperature, through the level of the metabolism and oxidative damage, shapes the properties of the mitochondrial genome.