Mitochondrial DNA and "performance enhancement"

3 minute read

One of the articles by Douglas Wallace referenced in the previous post covering mtDNA selection is subtitled "On the road to therapeutics and performance enhancement."

One theme of the review article is the adaptive value of mtDNA variants to different human populations. He discusses in some detail the role of some of this variation in high latitude populations as a possible cold adaptation, with variants that decrease ATP production, but generate more heat as a side effect. These same variants are associated with greater longevity, less degenerative disease, but more disorders of energy metabolism.

But Wallace doesn't say a single word about the obvious inverse of these observations: if some populations have high-frequency variants that decrease ATP production, doesn't it follow that the other populations have variants that don't decrease it?

True to its subtitle, the paper does include a section on "performance enhancement". It is a short section, which includes a conclusory paragraph for the paper as a whole, but here are the two relevant paragraphs:

It is now clear that not all mtDNA variation is deleterious. Indeed, about 25% of all ancient mtDNA variation appears to have caused functional mitochondrial changes and thus been adaptive. Those mtDNA variants that are adapted to warm climates have mtDNA variants that result in tightly coupled OXPHOS, thus maximizing ATP output and minimizing heat production. The presence of these mtDNAs permits maximum muscle performance but also predispose sedentary individuals that consume excess calories to multiple problems. They would be prone to be overweight and their mitochondria would generate excessive ROS, thus making them susceptile to a variety of degenerative diseases, cancer and premature aging. Partially uncoupled mitochondria generate more heat, but at the expense of ATP production. Individual's with these variants are better able to tolerate the cold, and are less prone to obesity. They also generate less ROS making then resistant to degenerative diseases and aging. Finally, the mitochondria are why we breathe. Hence, mitochondrial variation might be an important factor in individual predisposition to altitude sickness.
All of these factors and numerous others are areas that influence our daily lives. Consequently, some individuals may wish to change their energetic phenotype by changing their mtDNA genotype. If some people will undergo surgery to change their appearance, there will certainly be some who will submit to mtDNA alterations to change their life style, appearance, and physical performance. For example, changing a single mtDNA nucleotide of a high performance athlete to increase mitochondrial ATP production through altered OXPHOS coupling could increase performance by several percent and mean the difference between Olympic immortality versus obscurity. Since such a change would be undetectable by any reasonable standard screening procedure. Why wouldn't a competitive athlete take advantage of such an opportunity?

So Wallace tells us that there are population differences in mtDNA metabolism, that some variants common at low latitudes have higher ATP production than others, and that genetic engineering an individual to have one of these high-ATP producing mtDNA types might be a form of performance enhancement.

Am I the only one who senses something missing here? Is Wallace saying that the "difference between Olympic immortality versus obscurity" is already a result of mtDNA metabolic differences?

If Wallace is really saying that these low-latitude mtDNA variants may "increase performance by several percent", then isn't that the most explosive aspect of his paper?

And while I'm at it, why should it be that low-latitude populations have high-ATP-producing variants? As far as I can tell, it's a total mystery that isn't addressed in the least.


Wallace DC. 2005a. The mitochondrial genome in human adaptive radiation and disease: On the road to therapeutics and performance enhancement. Gene 354:169-180. Full text (subscription)