High diversity and no significant selection signal of human ADH1B gene in Tibet.
High diversity and no significant selection signal of human ADH1B gene in Tibet.
复制标题
西藏地区人类ADH1B基因多样性高且无显着选择信号
DOI：
10.1186/2041-2223-3-23
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发表时间：
2012-11-23
期刊：
影响因子：
--
通讯作者：
Li H
中科院分区：
文献类型：
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作者：
Lu Y;Kang L;Hu K;Wang C;Sun X;Chen F;Kidd JR;Kidd KK;Li H
ADH 1B基因是人类研究最多的基因之一，具有许多多态性位点。rs 1229984是编码Arg 48 His置换的单核苷酸多态性之一，与酒精中毒、消化系统肿瘤等多种严重疾病相关。ADH 1B * 48 His等位基因仅在东亚和西南亚出现频率较高，与农业高度相关。微进化研究已经基于包含该基因的七个SNP定义了ADH 1B的七个单倍型群。其中三个单倍型群H5、H6和H7含有ADH 1B * 48 His等位基因。H5在西南亚发现，另外两种在东亚发现。H7通过rs3811801的衍生等位基因衍生自H6。H7单倍型在汉族、苗族、朝鲜族、日本族、哈萨克族、蒙古族等人群中均表现出显著的正选择性，本研究通过对来自西藏自治区12个藏族群体的1,175名个体的ADH 1B基因区域内的23个SNPs进行分型，验证藏族是否也表现出正选择性。通过多个统计量的估计，研究了藏族和东亚其他人群中的基因差异和正选择信号。较大的藏族人口（昌都、拉萨、那曲、林芝、山南和日喀则）主要由农民组成，约有12%的H7和2%的H6。较小的人口，以狩猎为生或最近转向农业，H7频率较低（丁日9%，贡博8%，门巴和夏尔巴6%）。罗坝（2%）和邓（0%）的频率更低。长距离单倍型分析显示藏人中H7的正选择信号非常微弱。有趣的是，H7的单倍型多样性在西藏人中高于任何其他研究的人群，表明西藏人的单倍型群有更长的多样化历史。对长距离单倍型的网络分析表明，汉族人的H7不是来自藏族，而是来自两个群体的共同祖先。我们认为ADH 1B的H7起源于汉藏人群的祖先，并很早就流向了藏族。然而，由于藏族人对农作物的依赖较少，因此没有受到明显的选择影响。因此，H7并没有上升到一个高频率，而单倍型群的多样性已经积累到一个非常高的水平。
ADH1B is one of the most studied human genes with many polymorphic sites. One of the single nucleotide polymorphism (SNP), rs1229984, coding for the Arg48His substitution, have been associated with many serious diseases including alcoholism and cancers of the digestive system. The derived allele, ADH1B*48His, reaches high frequency only in East Asia and Southwest Asia, and is highly associated with agriculture. Micro-evolutionary study has defined seven haplogroups for ADH1B based on seven SNPs encompassing the gene. Three of those haplogroups, H5, H6, and H7, contain the ADH1B*48His allele. H5 occurs in Southwest Asia and the other two are found in East Asia. H7 is derived from H6 by the derived allele of rs3811801. The H7 haplotype has been shown to have undergone significant positive selection in Han Chinese, Hmong, Koreans, Japanese, Khazak, Mongols, and so on. In the present study, we tested whether Tibetans also showed evidence for selection by typing 23 SNPs in the region covering the ADH1B gene in 1,175 individuals from 12 Tibetan populations representing all districts of the Tibet Autonomous Region. Multiple statistics were estimated to examine the gene diversities and positive selection signals among the Tibetans and other populations in East Asia. The larger Tibetan populations (Qamdo, Lhasa, Nagqu, Nyingchi, Shannan, and Shigatse) comprised mostly farmers, have around 12% of H7, and 2% of H6. The smaller populations, living on hunting or recently switched to farming, have lower H7 frequencies (Tingri 9%, Gongbo 8%, Monba and Sherpa 6%). Luoba (2%) and Deng (0%) have even lower frequencies. Long-range haplotype analyses revealed very weak signals of positive selection for H7 among Tibetans. Interestingly, the haplotype diversity of H7 is higher in Tibetans than in any other populations studied, indicating a longer diversification history for that haplogroup in Tibetans. Network analysis on the long-range haplotypes revealed that H7 in the Han Chinese did not come from the Tibetans but from a common ancestor of the two populations. We argue that H7 of ADH1B originated in the ancestors of Sino-Tibetan populations and flowed to Tibetans very early. However, as Tibetans depend less on crops, and therefore were not significantly affected by selection. Thus, H7 has not risen to a high frequency, whereas the diversity of the haplogroup has accumulated to a very high level.