#actn3

id you know your DNA can reveal whether you’re built for endurance or power sports? The ACTN3 gene (the "speed gene") determines if you’re more likely to excel in sprinting or long-distance running. Meanwhile, PPARGC1A influences aerobic capacity, and ACE affects muscle efficiency.

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Yesterday, I came across a fascinating paper, which reports that a protein truncating variant in ACTN3 in the homozygous state (i.e. complete knockout of the protein) is extremely common worldwide.  It seems there are around 1.2 billion human knockouts for ACTN3 worldwide. 1.2 billion! (That is the number of humans living in India). If you’re wondering why this null variant became so common, there’s an extremely fascinating reason for that.

The gene ACTN3 codes for alpha-actinin-3, a muscle protein that is present only in the fast-twitching skeletal muscle. There are two skeletal muscle types--type 1 or slow twitching and type 2 or fast twitching. While the fast twitching muscle is used for rapid contractions that lasts for short duration (used during sprinting), the slow twitching muscle is used for sustained contraction that lasts for longer duration (used during endurance activities).

In the current paper, the authors show that individuals with the null mutation (XX) withstand cold for longer duration than individuals without the null mutation (RR). The authors immersed 15 XX and 27 RR individuals in cold water for around 2 hrs (with multiple 10 mins breaks,) and tested how many were able to maintain their core body temperature (measured from rectal temperature) above 35.5 degree Celsius. While only 30% of RR individuals maintained their core body temperature, around 70% of XX individuals did the same. That is a large difference. The authors didn’t explicitly mention any effect size estimate. But I calculated a crude estimate of OR-4.75 by making a 2x2 table from their data. That’s a large effect size, and it makes sense given that they were able to show a significant association in such an extremely small sample size.

It seems that this beneficial effect (ability to tolerate cold for long) has led to the positive selection of this null mutation. The authors speculate that the mutation must have provided the ancestral humans who migrated out of Africa a survival advantage against harsh cold climates.

Interestingly, the same mutation leads to decreased athletic ability, specifically sprinting ability (sprinting requires fast twitching muscle, which the XX individuals cannot use). A previous paper shows that the XX genotype is underrepresented in elite sprint athletes. Again, I crudely calculated the effect size by making 2x2 table comparing only XX and RR genotype individuals (to make the effect sizes comparable between the two studies,) and found that the effect size is OR-0.18 (inverse OR-5.5), which is similar but opposite in direction to the XX’s effect size for cold tolerance (OR-4.75).

Tip: ACTN3 – The Muscle Gene

Tip: ACTN3 – The Muscle Gene

The ACTN3 gene is in large part responsible for the type of muscle tissue that you have. Not only the muscle fiber dominance, but also the various qualities of the tissue itself – how well it handles muscle damage, how much mTOR is activated, its capacity to use oxygen for fuel, etc.

You have two main types of ACTN3. The X variant is better suited for endurance…

Tip: ACTN3 – The Muscle Gene

Tip: ACTN3 – The Muscle Gene

The ACTN3 gene is in large part responsible for the type of muscle tissue that you have. Not only the muscle fiber dominance, but also the various qualities of the tissue itself – how well it handles muscle damage, how much mTOR is activated, its capacity to use oxygen for fuel, etc.

You have two main types of ACTN3. The X variant is better suited for endurance…

Tip: ACTN3 – The Muscle Gene

Tip: ACTN3 – The Muscle Gene

The ACTN3 gene is in large part responsible for the type of muscle tissue that you have. Not only the muscle fiber dominance, but also the various qualities of the tissue itself – how well it handles muscle damage, how much mTOR is activated, its capacity to use oxygen for fuel, etc.

You have two main types of ACTN3. The X variant is better suited for endurance…

ACTN3 and the super-sprinter gene (I got it)

ACTN3 and the super-sprinter gene is the gene found in elite athletes around the world. The ACTN3 makes a special protein This the “…controls fast-twitch muscle fibers, the cells responsible for the speedy tensing and flexing of the muscles involved in sprinting or weight-lifting“. Many elite athletes have one mutation, I was surprised when my 23andme results (see below) said that I had two…