More than a billion humans worldwide are predicted to be completely deficient in the fast skeletal muscle fiber protein α-actinin-3 owing to homozygosity for a premature stop codon polymorphism, R577X, in the ACTN3 gene. The R577X polymorphism is associated with elite athlete status and human muscle performance, suggesting that α-actinin-3 deficiency influences the function of fast muscle fibers. Here we show that loss of α-actinin-3 expression in a knockout mouse model results in a shift in muscle metabolism toward the more efficient aerobic pathway and an increase in intrinsic endurance performance. In addition, we demonstrate that the genomic region surrounding the 577X null allele shows low levels of genetic variation and recombination in individuals of European and East Asian descent, consistent with strong, recent positive selection. We propose that the 577X allele has been positively selected in some human populations owing to its effect on skeletal muscle metabolism.
ScienceNow has a good good summary of the background information:
There are two types of skeletal muscle fibers. Fast fibers, which use sugars for fuel and do not require oxygen, kick in for tasks that require maximum force and quick action, such as sprinting. Slow fibers, which employ oxygen-using (or aerobic) pathways, power activities that require endurance, such as long-distance running. A protein called alpha-actinin-3 is made mostly by fast fibers and is implicated in their capacity for rapid force generation. About 18% of people of European descent do not produce the protein at all due to mutations in both their copies of the gene ACTN3, which codes for alpha-actinin-3. Previous studies have shown that endurance athletes such as long-distance runners have higher frequencies of this mutation, whereas sprinters and athletes in other sports that require quick muscle strength have lower frequencies.
I doubt that European and Asian populations (in this case they used the HapMap samples, whites from Utah and Chinese and Japanese) were selected for marathon running, rather, it seems plausible that this sort of metabolic reshaping has other consequences and implications. The timing of the selective sweeps is around 15,000 years before the present for Europeans and 33,000 for Asians. These are very preliminary numbers obviously (noted by the authors), but they seem a bit old for "maybe it's agriculture." Off the top of my head I wonder if this has something to do with colder climates. In any case, also keep in mind that the "Africans" in this sample were Yoruba from Nigeria. I think everyone is curious to see how the Kalenjin of Kenya pan out....
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Hey Razib,
This is my baby (as in, I'm first author on the paper).
We thought about selection for cold tolerance, but our latest data on global distribution of the null allele don't really fit with that. Most likely it's something to do with famine resistance, although we're not ruling out the idea that it's selection for some sort of muscle performance phenotype (it's surprising how many muscle genes are popping up in recent genome-wide scans for selection).
We haven't got genotype distributions for the Kalenjin yet, but we have a paper due out soon that shows a disappointingly low frequency of the null allele in Kenyans in general, and no association with athletic performance in that population. Looks like other genes (and environmental factors) are responsible for the spectacular endurance performance of East Africans.