人群肤色的多样性是现代人 (Homo sapiens) 10万年前走出非洲之后为了适应新环境而产生的表型变化。随着人类群体遗传学研究的深入开展，人们已经发现了一些色素基因与欧洲人群肤色变浅有着密切的联系。东亚人群也是研究现代人肤色进化的理想人群，因为他们同样是生活在较高纬度地区的浅肤色人群。然而，到目前为止针对东亚人群的肤色研究仍不系统，东亚人群肤色变浅的遗传机制尚不清楚。本研究采用全基因组序列多态性系统比较的方法，深入地分析了色素基因与东亚人群肤色之间的关系。通过比较浅肤色的汉族人群和深肤色的南亚语系人群在全基因组水平上的遗传差异，我们发现了一个重要的色素基因 OCA2在汉族人群中受到了强烈的达尔文正向选择的作用。进一步的分子进化分析显示，OCA2基因上的一个氨基酸替代突变rs1800414 (His615Arg)在浅肤色的汉族人群中频率很高(59%)，在深肤色的南亚语系人群中相对较低(14%)，而非洲人和欧洲人群中却没有此突变。遗传相关性分析和细胞水平的功能实验表明，该氨基酸突变与东亚人群的肤色表型以及黑色素的合成具有非常显著的相关性。综合多方面的实验证据，我们认为东亚人群的肤色变浅是由于色素相关基因在东亚人群中受到了正向选择。并且，在东亚人群中受到选择的色素基因与欧洲人群中报道的基因不同，表明东亚人群与欧洲人群的肤色变浅是独立发生的趋同进化事件。; Skin lightening among Eurasians is considered an adaptation to novel high latitude environments encountered by modern humans (Homo sapiens) exiting Africa ~100,000 years ago. In Europeans, several responsible genes for lightening have been found, but for East Asians the situation remains unclear. East Asians are ideal populations for skin color evolution as they are also light-skinned populations living in high latitude area. Through genome-wide comparision of sequence variations between light-skinned Han Chinese and dark-skinned Austro-Asiatic speaking populaitons, we aim to detect the role of pigmentation genes in skin lightening of East Asian populations. We observed a strong and East-Asian-specific signal of Darwinian positive selection on the pigmentation gene OCA2. An amino acid substitution of OCA2 prevalent in most eastern Asian populations (59%)—but rare in Austro-Asiatic speakers (14%) and absent in Africans and Europeans—was significantly associated with skin lightening in northern Han Chinese due to reduced melanin production. Our results support the proposed convergent evolution of skin pigmentation in Europe and East Asia during recent human evolutionary history.
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