Rana B K, Hewett-Emmett D, Jin L, Chang B H, Sambuughin N, Lin M, Watkins S, Bamshad M, Jorde L B, Ramsay M, Jenkins T, Li W H
Human Genetics Center, School of Public Health and Graduate School of Biomedical Sciences, University of Texas, Houston, Texas 77030, USA.
Genetics. 1999 Apr;151(4):1547-57. doi: 10.1093/genetics/151.4.1547.
Variation in human skin/hair pigmentation is due to varied amounts of eumelanin (brown/black melanins) and phaeomelanin (red/yellow melanins) produced by the melanocytes. The melanocortin 1 receptor (MC1R) is a regulator of eu- and phaeomelanin production in the melanocytes, and MC1R mutations causing coat color changes are known in many mammals. We have sequenced the MC1R gene in 121 individuals sampled from world populations with an emphasis on Asian populations. We found variation at five nonsynonymous sites (resulting in the variants Arg67Gln, Asp84Glu, Val92Met, Arg151Cys, and Arg163Gln), but at only one synonymous site (A942G). Interestingly, the human consensus protein sequence is observed in all 25 African individuals studied, but at lower frequencies in the other populations examined, especially in East and Southeast Asians. The Arg163Gln variant is absent in the Africans studied, almost absent in Europeans, and at a low frequency (7%) in Indians, but is at an exceptionally high frequency (70%) in East and Southeast Asians. The MC1R gene in common and pygmy chimpanzees, gorilla, orangutan, and baboon was sequenced to study the evolution of MC1R. The ancestral human MC1R sequence is identical to the human consensus protein sequence, while MC1R varies considerably among higher primates. A comparison of the rates of substitution in genes in the melanocortin receptor family indicates that MC1R has evolved the fastest. In addition, the nucleotide diversity at the MC1R locus is shown to be several times higher than the average nucleotide diversity in human populations, possibly due to diversifying selection.
人类皮肤/毛发色素沉着的差异是由于黑素细胞产生的真黑素（棕色/黑色黑色素）和褐黑素（红色/黄色黑色素）数量不同所致。黑皮质素1受体（MC1R）是黑素细胞中真黑素和褐黑素生成的调节因子，在许多哺乳动物中，已知MC1R突变会导致毛色变化。我们对来自世界人群（重点是亚洲人群）的121名个体的MC1R基因进行了测序。我们在五个非同义位点发现了变异（导致产生了Arg67Gln、Asp84Glu、Val92Met、Arg151Cys和Arg163Gln变异体），但仅在一个同义位点（A942G）发现了变异。有趣的是，在所研究的所有25名非洲个体中都观察到了人类共有蛋白序列，但在其他被检测人群中的频率较低，尤其是在东亚和东南亚人群中。所研究的非洲人中不存在Arg163Gln变异体，欧洲人中几乎不存在，印度人中频率较低（7%），但在东亚和东南亚人群中频率异常高（70%）。对普通黑猩猩、侏儒黑猩猩、大猩猩、猩猩和狒狒的MC1R基因进行了测序，以研究MC1R的进化。人类祖先的MC1R序列与人类共有蛋白序列相同，而MC1R在高等灵长类动物中差异很大。对黑皮质素受体家族基因替换率的比较表明，MC1R进化得最快。此外，MC1R基因座的核苷酸多样性比人类群体中的平均核苷酸多样性高出几倍，这可能是由于多样化选择所致。
