R577X Polymorphism of Alpha-Actinin-3 in the Human Populations of Northeastern Asia

Abstract

In polymorphism rs1815739, a C → T transition converts arginine to a premature stop-codon at residue 577 of the α-actinin-3 (ACTN3) protein (R577X polymorphism). This polymorphism may affect muscle performance, and the derived 577X allele is found to be underrepresented in sprinters/power athletes. In addition, loss of α-actinin-3 was reported to result in a shift in the metabolism of muscles toward a more efficient aerobic pathway. This suggests that this polymorphism may have been involved in enhancing the capability for hunting and adapting to cold during the evolution of humans. In this study, we investigated the rs1815739 polymorphism in several native populations (Chukchi, Koryaks, and Evens) and later settlers (Russians) in Northeast Asia. The genomic DNA was isolated from the peripheral blood. ACTN3 genotypes for the rs1815739 locus were established by the enzymatic digestion of amplicons with DdeI. Homozygotes TT were confirmed by DNA sequencing. We found lowered frequencies (less than 40%) of the mutant rs1815739-T allele in the studied populations of Northeastern Asia. Analysis of the exome data has shown that haplotypes comprising the rs1815739-T allele reach the highest frequencies in the populations of Southern and Central Siberia. In contrast, this haplotype is rather rare in Northeast Siberia. The obtained results contradict the hypothesis that the rs1815739 polymorphism may have been involved in the adaptation of Northeast Siberians to cold.