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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.

ACTN3 Allele Frequency in Humans Covaries with Global Latitudinal Gradient