Akey Joshua M, Zhang Ge, Zhang Kun, Jin Li, Shriver Mark D
Center for Genome Information, University of Cincinnati, Cincinnati, Ohio, USA.
Genome Res. 2002 Dec;12(12):1805-14. doi: 10.1101/gr.631202.
Identifying genomic regions that have been targets of natural selection remains one of the most important and challenging areas of research in genetics. To this end, we report an analysis of 26,530 single nucleotide polymorphisms (SNPs) with allele frequencies that were determined in three populations. Specifically, we calculated a measure of genetic differentiation, F(ST), for each locus and examined its distribution at the level of the genome, the chromosome, and individual genes. Through a variety of analyses, we have found statistically significant evidence supporting the hypothesis that selection has influenced extant patterns of human genetic variation. Importantly, by contrasting the F(ST) of individual SNPs to the empirical genome-wide distribution of F(ST), our results are not confounded by tenuous assumptions of population demographic history. Furthermore, we have identified 174 candidate genes with distribution of genetic variation that indicates that they have been targets of selection. Our work provides a first generation natural selection map of the human genome and provides compelling evidence that selection has shaped extant patterns of human genomic variation.
识别出经历过自然选择的基因组区域，仍然是遗传学研究中最重要且最具挑战性的领域之一。为此，我们报告了对26530个单核苷酸多态性（SNP）的分析，这些SNP的等位基因频率是在三个人群中测定的。具体而言，我们计算了每个位点的遗传分化指标F(ST)，并在基因组、染色体和单个基因水平上研究了它的分布。通过各种分析，我们发现了具有统计学意义的证据，支持选择影响了人类遗传变异现存模式这一假设。重要的是，通过将单个SNP的F(ST)与全基因组F(ST)的经验分布进行对比，我们的结果不会受到群体人口历史的微弱假设的混淆。此外，我们已经识别出174个候选基因，其遗传变异分布表明它们是选择的目标。我们的工作提供了第一代人类基因组自然选择图谱，并提供了令人信服的证据，证明选择塑造了人类基因组变异的现存模式。
