Can the same genes both improve your aptitude for endurance exercise and lower your life expectancy? A recent study of mitochondrial DNA (mtDNA) in track athletes suggests that the answer may be `yes'.

The mitochondrial genome is a small (17-kb), circular chromosome that encodes 13 components of the electron transport chain, which generate the proton gradient necessary for aerobic ATP production. Mitochondrial DNA might therefore be expected to influence an individual's ability to sustain long periods of exercise. To determine whether the mitochondrial genes of track athletes differ systematically from those of the population at large, Niemi and Majamaa analyzed the mtDNA sequences of 141 elite Finnish long-distance runners and sprinters as well as 1060 Finnish control subjects. They found that certain groups of mtDNA sequences (called haplogroups, since there is only one copy of the chromosome per mitochondrion) occurred less frequently in the distance runners than in the sprinters and control subjects. In particular, no distance runner belonged to haplogroup K or subhaplogroup J2,whose combined frequency is at least 4.5% among control subjects and is even higher among sprinters.

Since distance runners are heavily dependent on aerobic ATP production by their mitochondria, it isn't surprising that their mtDNA differs from that of people with different exercise habits. For example, genes for protein isoforms that mildly impair ATP synthesis should presumably be rare among endurance athletes. What's interesting, however, is that the haplogroups underrepresented among the distance runners are overrepresented among very old people. Previous work by the Niemi/Majamaa group and others has shown that members of haplogroup K and subhaplogroup J2 tend to live longer than people of other haplogroups.

Is it plausible that the mitochondrial genes of haplogroup K and subhaplogroup J2 limit endurance performance but improve life expectancy?Niemi and Majamaa offer an intriguing hypothesis to explain this potential paradox: perhaps J2 and K are `uncoupling genomes' that increase proton leak across the mitochondrial membrane. An elevated proton leak could certainly limit aerobic ATP production, and thus endurance performance. But it could also prevent the mitochondrial membrane potential from rising into the range(>140 mV) where production of reactive oxygen species (ROS) becomes high. ROS have been implicated in ageing, so limiting ROS production could contribute to a longer life. Although the link between ROS and ageing is still under investigation, several mouse studies have suggested that relatively`leaky' mitochondria could promote longevity by minimizing the generation of ROS. Thus, if members of J2 and K haplotypes limit their ROS production, this could explain why they live longer than other people.

If the rareness of J2 and K among endurance athletes is confirmed by additional work, the `uncoupling genome' hypothesis should be tested with biochemical measurements of mitochondria isolated from representatives of different haplogroups. If the hypothesis is correct, mitochondria of haplogroup K and subhaplogroup J2 should have lower membrane potentials, lower ROS production rates and lower ATP production rates (relative to O2consumption rates) than other mitochondria. Such studies would represent the completion of another lap in our race to understand the genetic basis of differences in athletic performance.

Niemi, A. K. and Majamaa, K. (
). Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes.
Eur. J. Hum. Gen.