A variant of a gene associated with elite athletic performance has been subject to strong, recent positive selection in humans, according to a study published online in Nature Genetics. Experiments on mice suggest that this variant may promote more efficient muscle metabolism.
The gene ACTN3, encoding alpha-actinin-3, is specifically expressed in the fast-twitch muscle fibers that are responsible for generating force at high velocity. ACTN3 exists in a non-functional truncated form in more than a billion people worldwide, and is overrepresented in endurance athletes. By contrast, the functional form is overrepresented in elite sprinters. Kathryn North and colleagues examined the extent of genetic variation in the vicinity of ACTN3 in individuals with the truncated version. They found very little variation, which is consistent with the truncated version of the gene being under positive selection.
To understand better the effect of the truncation on muscle function, the authors generated a line of mice lacking ACTN3, and found that there is a shift in muscle metabolism toward the more efficient aerobic pathway. These mice were also able to run on average 33% further before reaching exhaustion than mice with normal ACTN3 function. The authors conclude that this increased metabolic efficiency could explain the overrepresentation of the truncated form of ACTN3 in endurance athletes.
Kathryn North (Children's Hospital at Westmead, Sydney, Australia)
Abstract available online.
(C) Nature Genetics press release.
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