Why is α-actinin-3 deficiency so common in the general population? The evolution of athletic performance

Abstract

The human ACTN3 gene encodes the protein α-actinin-3, a component of the contractile apparatus in fast skeletal muscle fibers. In 1999, we identified a common polymorphism in ACTN3 (R577X) that results in absence of α-actinin-3 in more than one billion people worldwide, despite the ACTN3 gene being highly conserved during human evolution. In 2003, we demonstrated that ACTN3 genotype influences elite athletic performance, and the association between ACTN3 genotype and skeletal muscle performance has since been replicated in athletes and non-athlete cohorts. We have also studied the evolution of the R577X allele during human evolution and demonstrated that the null (X) allele has undergone str..