Mitochondria, sex and variation in routine metabolic rate

Variation in the metabolic costs associated with organismal maintenance may play a key role in determining fitness, and thus these differences among individuals are likely to be subject to natural selection. Although the evolvability of maintenance metabolism depends on its underlying genetic architecture, relatively little is known about the nature of genetic variation that underlies this trait. To address this, we measured variation in routine metabolic rate (ṀO₂ᵣₒᵤₜᵢₙₑ), an index of maintenance metabolism, within and among three populations of Atlantic killifish, Fundulus heteroclitus, including a population from a region of genetic admixture between two subspecies. Polygenic association tests among individuals from the admixed population identified 54 single nucleotide polymorphisms (SNPs) that were associated with ṀO₂ᵣₒᵤₜᵢₙₑ, and these SNPs accounted for 43% of interindividual variation in this trait. However, genetic associations with ṀO₂ᵣₒᵤₜᵢₙₑ involved different SNPs if females and males were analysed separately, and there was a sex‐dependent effect of mitochondrial genotype on variation in routine metabolism. These results imply that there are sex‐specific genetic mechanisms, and potential mitonuclear interactions, that underlie variation in ṀO₂ᵣₒᵤₜᵢₙₑ. Additionally, there was evidence for epistatic interactions between 17% of the possible pairs of trait‐associated SNPs, suggesting that epistatic effects on ṀO₂ᵣₒᵤₜᵢₙₑ are common. These data demonstrate not only that phenotypic variation in this ecologically important trait has a polygenic basis with considerable epistasis among loci, but also that these underlying genetic mechanisms, and particularly the role of mitochondrial genotype, may be sex‐specific.