High polymorphism at the human melanocortin 1 receptor locus.
High polymorphism at the human melanocortin 1 receptor locus.
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人黑皮质素 1 受体基因座的高度多态性。
DOI：
10.1093/genetics/151.4.1547
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发表时间：
1999
期刊：
影响因子：
3.3
通讯作者：
Li,WH
中科院分区：
文献类型：
--
作者：
Rana,BK;Hewett-Emmett,D;Jin,L;Chang,BH;Sambuughin,N;Lin,M;Watkins,S;Bamshad,M;Jorde,LB;Ramsay,M;Jenkins,T;Li,WH
人类皮肤/毛发色素沉着的变化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）的量不同。黑皮质素1受体（MC 1 R）是黑素细胞中黑素和褐黑素产生的调节剂，并且已知在许多哺乳动物中引起毛色变化的MC 1 R突变。我们已经测序了MC 1 R基因在121个人从世界人口中采样，重点是亚洲人口。我们发现在五个非同义位点（导致变体Arg 67 Gln，Asp 84 Glu，Val 92 Met，Arg 151 Cys和Arg 163 Gln）的变异，但只有一个同义位点（A942 G）。有趣的是，在研究的所有25个非洲个体中观察到了人类共有蛋白序列，但在其他人群中的频率较低，特别是在东亚和东南亚人中。Arg 163 Gln变异在研究的非洲人中不存在，在欧洲人中几乎不存在，在印度人中的频率较低（7%），但在东亚和东南亚人中的频率异常高（70%）。对普通黑猩猩、侏儒黑猩猩、大猩猩、猩猩和狒狒的MC 1 R基因进行测序，以研究MC 1 R的进化。祖先人类MC 1 R序列与人类共有蛋白序列相同，而MC 1 R在高等灵长类动物中变化很大。对黑皮质素受体家族中基因替换率的比较表明，MC 1 R进化最快。此外，MC 1 R基因座的核苷酸多样性比人类群体的平均核苷酸多样性高出数倍，这可能是由于多样化选择。
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.