Global Patterns of Diversity and Selection in Human Tyrosinase Gene

Global variation in skin pigmentation is one of the most striking examples of environmental adaptation in humans. More than two hundred loci have been identified as candidate genes in model organisms and a few tens of these have been found to be significantly associated with human skin pigmentation in genome-wide association studies. However, the evolutionary history of different pigmentation genes is rather complex: some loci have been subjected to strong positive selection, while others evolved under the relaxation of functional constraints in low UV environment. Here we report the results of a global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, to assess the role of its variation in the evolution of skin pigmentation differences among human populations. We observe a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints. A similar pattern was previously observed in the MC1R gene and concurs with UV radiation-driven model of skin color evolution by which mutations leading to lower melanin levels and decreased photoprotection are subject to purifying selection at low latitudes while being tolerated or even favored at higher latitudes because they facilitate UV-dependent vitamin D production. Our coalescent date estimates suggest that the non-synonymous variants, which are frequent in Europe and North Africa, are recent and have emerged after the separation of East and West Eurasian populations.

人类皮肤色素沉着的全球差异，是人类环境适应性最显著的例证之一。在模式生物中，已有超过200个基因座被鉴定为候选基因，其中数十个基因座在全基因组关联研究中被证实与人类皮肤色素沉着显著相关。然而，不同色素沉着相关基因的演化历程颇为复杂：部分基因座受到强烈的正向选择作用，而另一些则在低紫外辐射环境中经历了功能约束的松弛化演化。本研究针对人类酪氨酸酶（tyrosinase）基因展开全球范围的分析——该基因是黑色素生成过程中的关键酶之一——旨在评估其序列变异在人类群体间皮肤色素沉着差异演化中的作用。我们在欧洲人群样本中观察到更高的非同义多态性频率，这与选择约束的松弛现象相一致。此前在MC1R基因中也观察到了类似的模式，这与紫外辐射驱动的皮肤颜色演化模型相符：该模型指出，导致黑色素水平降低、光保护作用减弱的突变，在低纬度地区会受到纯化选择的约束，但在高纬度地区则可被耐受甚至受到青睐——因为这类突变可促进依赖紫外辐射的维生素D合成。我们的溯祖时间估算结果显示，在欧洲和北非人群中高频出现的非同义变异是新近产生的，且其出现时间晚于欧亚东西人群的分化事件。