Detection of the signature of natural selection in humans: Evidence from the Duffy blood group locus
Detection of the signature of natural selection in humans: Evidence from the Duffy blood group locus
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DOI：
10.1086/302879
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发表时间：
2000-05-01
影响因子：
9.8
通讯作者：
Di Rienzo, A
中科院分区：
文献类型：
--
作者：
Hamblin, MT;Di Rienzo, A
Duffy血型基因座编码一种趋化因子受体，由三个等位基因FY* a、FY*B和FY*O组成。FY*O等位基因的频率与红细胞上不存在FY抗原相对应，在大多数撒哈拉以南非洲人群中处于或接近固定状态，但在非洲以外非常罕见。FY*O等位基因的F-ST值是人类所有等位基因中观察到的最高的，为该基因座的自然选择作用提供了强有力的证据。FY*O等位基因的纯合性赋予间日疟疾完全抗性，这表明该等位基因已成为间日疟原虫或其他感染因子选择的目标。为了表征该位点的定向选择特征，我们调查了17个意大利人和来自5个撒哈拉以南非洲人群的24个个体的DNA序列变异，包括以FY*O突变位点为中心的1.9 kb区域和距离它5-6 kb的1 kb区域。在这两个地区，非洲人的差异水平比意大利人低2 - 3倍。因此，汇总的非洲样本显示出对隔离地点数量的中性预期有很大偏离，而意大利样本则没有。FY*O等位基因出现在五个非洲人群中的三个的两个主要单倍型上。这一发现可能是由于重组、复发性突变、种群结构和/或突变积累和漂移。虽然我们无法区分这些不同的假设，但这两种主要的单倍型很可能是在FY*O突变的选择之前产生的。
The Duffy blood group locus, which encodes a chemokine receptor, is characterized by three alleles-FY*A, FY*B, and FY*O. The frequency of the FY*O allele, which corresponds to the absence of Fy antigen on red blood cells, is at or near fixation in most sub-Saharan African populations but is very rare outside Africa. The F-ST value for the FY*O allele is the highest observed for any allele in humans, providing strong evidence for the action of natural selection at this locus. Homozygosity for the FY*O allele confers complete resistance to vivax malaria, suggesting that this allele has been the target of selection by Plasmodium vivax or some other infectious agent. To characterize the signature of directional selection at this locus, we surveyed DNA sequence variation, both in a 1.9-kb region centered on the FY*O mutation site and in a 1-kb region 5-6 kb away from it, in 17 Italians and in a total of 24 individuals from five sub-Saharan African populations. The level of variation across both regions is two- to threefold lower in the Africans than in the Italians. As a result, the pooled African sample shows a significant departure from the neutral expectation for the number of segregating sites, whereas the Italian sample does not. The FY*O allele occurs on two major haplotypes in three of the five African populations. This finding could be due to recombination, recurrent mutation, population structure, and/or mutation accumulation and drift. Although we are unable to distinguish among these alternative hypotheses, it is likely that the two major haplotypes originated prior to selection on the FY*O mutation.