title: The evolution of skeletal muscle performance: gene duplication and divergence of human sarcomeric alpha-actinins.
abstract: In humans, there are two skeletal muscle alpha-actinins, encoded by ACTN2 and ACTN3, and the ACTN3 genotype is associated with human athletic performance. Remarkably, approximately 1 billion people worldwide are deficient in alpha-actinin-3 due to the common ACTN3 R577X polymorphism. The alpha-actinins are an ancient family of actin-binding proteins with structural, signalling and metabolic functions. The skeletal muscle alpha-actinins diverged approximately 250-300 million years ago, and ACTN3 has since developed restricted expression in fast muscle fibres. Despite ACTN2 and ACTN3 retaining considerable sequence similarity, it is likely that following duplication there was a divergence in function explaining why alpha-actinin-2 cannot completely compensate for the absence of alpha-actinin-3. This paper focuses on the role of skeletal muscle alpha-actinins, and how possible changes in functions between these duplicates fit in the context of gene duplication paradigms.
authors.affiliation: Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: Monkol
authors.initials: M
authors.lastname: Lek
authors.forename: Kate G R
authors.initials: KG
authors.lastname: Quinlan
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
mesh_terms: D000185:Actinin / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D019143:Evolution, Molecular; D018628:Gene Dosage; D020440:Gene Duplication; D014644:Genetic Variation; D006801:Humans; D008957:Models, Genetic; D008958:Models, Molecular; D020409:Molecular Motor Proteins / Q000235:genetics / Q000502:physiology; D053580:Muscle Strength / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D054730:Protein Interaction Domains and Motifs
chemical_list: C401401:ACTN2 protein, human; C118456:ACTN3 protein, human; D020409:Molecular Motor Proteins; D000185:Actinin