Abstract

The α‐actinins are an ancient family of actin‐binding proteins that play structural and regulatory roles in cytoskeletal organisation and muscle contraction. α‐actinin‐3 is the most‐highly specialised of the four mammalian α‐actinins, with its expression restricted largely to fast glycolytic fibres in skeletal muscle. Intriguingly, a significant proportion (∼18%) of the human population is totally deficient in α‐actinin‐3 due to homozygosity for a premature stop codon polymorphism (R577X) in the ACTN3 gene. Recent work in our laboratory has revealed a strong association between R577X genotype and performance in a variety of athletic endeavours. We are currently exploring the function and evolutionary history of the ACTN3 gene and other α‐actinin family members. The α‐actinin family provides a fascinating case study in molecular evolution, illustrating phenomena such as functional redundancy in duplicate genes, the evolution of protein function, and the action of natural selection during recent human evolution. BioEssays 26:786–795, 2004. © 2004 Wiley Periodicals, Inc.