Differing Evolutionary Histories of the <i>ACTN3*R577X</i> Polymorphism among the Major Human Geographic Groups

It has been proposed that the functional ACTN3*R577X polymorphism might have evolved due to selection in Eurasian human populations. To test this possibility we surveyed all available population-based data for this polymorphism and performed a comprehensive evolutionary analysis of its genetic diversity, in order to assess the action of adaptive and random mechanisms on its variation across human geographical distribution. The derived 577X allele increases in frequency with distance from Africa, reaching the highest frequencies on the American continent. Positive selection, detected by an extended haplotype homozygosisty test, was consistent only with the Eurasian data, but simulations with neutral models could not fully explain the results found in the American continent. It is possible that particularities of Native American population structure could be responsible for the observed allele frequencies, which would have resulted from a complex interaction between selective and random factors.有研究提出，功能性ACTN3*R577X多态性可能是在欧亚人群的选择压力下演化而来。为验证这一假说，我们搜集了该多态性的所有可获取的人群层面研究数据，并对其遗传多样性展开了全面的演化分析，以评估适应性与随机演化机制在该多态性的全球地理分布变异中的作用。结果显示，衍生型577X等位基因的频率随与非洲的距离增加而升高，在美洲大陆达到峰值频率。通过延伸单倍型纯合度（extended haplotype homozygosity, EHH）检验检测到的正选择信号，仅在欧亚人群的研究数据中得到验证，但中性模型的模拟结果无法完全解释美洲大陆的观测结果。由此推测，美洲原住民人群结构的特殊性或许是导致观测到的等位基因频率的成因，而该频率实为选择因素与随机因素复杂相互作用的产物。