Abstract
A premature stop codon in ACTN3 resulting in α-actinin-3 deficiency (the ACTN3 577XX genotype) is common in humans and reduces strength, muscle mass, and fast-twitch fiber diameter, but increases the metabolic efficiency of skeletal muscle. Linkage disequilibrium data suggest that the ACTN3 R577X allele has undergone positive selection during human evolution. The allele has been hypothesized to be adaptive in environments with scarce resources where efficient muscle metabolism would be selected. Here we test this hypothesis by using recently developed comparative methods that account for evolutionary relatedness and gene flow among populations. We find evidence that the ACTN3 577XX genotype evolved in association with the global latitudinal gradient. Our results suggest that environmental variables related to latitudinal variation, such as species richness and mean annual temperature, may have influenced the adaptive evolution of ACTN3 577XX during recent human history.
Highlights
Genes important for metabolism include the a-actinin family that code for contractile proteins in muscle [1]
Two different genes code for skeletal muscle a-actinins: ACTN2 is expressed in all skeletal muscle fibers, while ACTN3 is expressed in fast-twitch muscle fibers
Approximately 18% of the human population is homozygous for an allele (R577X) that contains a premature stop codon in ACTN3 [3,4]
Summary
Genes important for metabolism include the a-actinin family that code for contractile proteins in muscle [1]. It is plausible that differences in the frequency of ACTN3 577XX may have arisen during the recent past, in relation to the global latitudinal gradient. We test the ACTN3 577XX adaptation hypothesis using global genotype and biodiversity data, with Bayesian comparative methods that account for phylogeny and migration.
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