ACTN3 - born to run?

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This week we turn the spotlight to the protein α-actinin-3. Encoded by ACTN3, sometimes dubbed the speed gene, α -actinin-3 is primarily expressed in type 2 "fast-twitch" skeletal muscle fibers. It cross-links and stabilizes actin thin filaments at the Z-line separating each muscle unit and is fundamental for producing the quick and powerful muscle contractions needed for activities like sprinting, jumping, and weightlifting (North, 1999).

Interestingly, not everyone has a functional ACTN3 protein. About 1.5 billion people worldwide have a single nucleotide polymorphism (R577X) that results in the replacement of an arginine with a premature stop codon (Goleva-Fjellet, 2020). It is widely accepted that the ensuing α-actinin-3 deficiency is compensated for by another actinin isoform, α-actinin-2, and muscle fiber composition does not appear to be affected (Del Coso, 2019).

Still research has shown that elite sprinters and power athletes are more likely to be homozygous for the functional version of the ACTN3 gene compared to the general population, suggesting it confers a genetic edge in high-intensity sports (Del Coso, 2019; Erskine, 2014; Yang, 2003) For endurance activities, an inverse relationship was initially proposed as one study reported a higher frequency of the XX genotype in elite endurance athletes ( Yang, 2003). While this would help explain why the genotype has been maintained by natural selection at the curiously high rate of circa 18 %, several subsequent studies were unable to replicate these findings ( Papadimitriou, 2018; Saunders, 2007).

However, there's no reason to worry about achieving your athletic goals even if you completely lack α-actinin-3. Genetics is only one factor out of multiple that determines physical prowess, but by exploring the proteins involved we can learn how to enhance or offset their effects.