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Identification of a Tibetan-Specific Mutation in the Hypoxic Gene EGLN1 and Its Contribution to High-Altitude Adaptation
文献类型：期刊论文
| 作者 | Xiang K1,2; Ouzhuluobu3; Peng Y1; Yang ZH1,2; Zhang XM1,2; Cui CY3; Zhang H1; Li M1,2; Zhang YF1; Bianba3 |
| 刊名 | MOLECULAR BIOLOGY AND EVOLUTION
 |
| 出版日期 | 2013 |
| 卷号 | 30期号:8页码:1889-1898 |
| 关键词 | EGLN1 positive selection hypoxic adaptation Tibetans |
| 通讯作者 | qixuebin@mail.kiz.ac.cn ; sub@mail.kiz.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | Tibetans are well adapted to high-altitude hypoxic conditions, and in recent genome-wide scans, many candidate genes have been reported involved in the physiological response to hypoxic conditions. However, the limited sequence variations analyzed in previous studies would not be sufficient to identify causal mutations. Here we conducted resequencing of the entire genomic region (59.4 kb) of the hypoxic gene EGLN1 (one of the top candidates from the genome-wide scans) in Tibetans and identified 185 sequence variations, including 13 novel variations (12 substitutions and 1 insertion or deletion). There is a nonsynonymous mutation (rs186996510, D4E) showing surprisingly deep divergence between Tibetans and lowlander populations (F-ST = 0.709 between Tibetans and Han Chinese). It is highly prevalent in Tibetans (70.9% on average) but extremely rare in Han Chinese, Japanese, Europeans, and Africans (0.56-2.27%), suggesting that it might be the causal mutation of EGLN1 contributing to high-altitude hypoxic adaptation. Neutrality test confirmed the signal of Darwinian positive selection on EGLN1 in Tibetans. Haplotype network analysis revealed a Tibetan-specific haplotype, which is absent in other world populations. The estimated selective intensity (0.029 for the C allele of rs186996510) puts EGLN1 among the known genes that have undergone the strongest selection in human populations, and the onset of selection was estimated to have started at the early Neolithic (similar to 8,400 years ago). Finally, we detected a significant association between rs186996510 and hemoglobin levels in Tibetans, suggesting that EGLN1 contributes to the adaptively low hemoglobin level of Tibetans compared with acclimatized lowlanders at high altitude. |
| 资助信息 | This work was supported by the National 973 Program of China (2012CB518202 to T.W. and X.Q., 2011CB512107 to Ou.), the National Natural Science Foundation of China (91231203 and 31123005 to B.S., and 91131001 to H.S.), State Key Laboratory of Genetic Resources and Evolution (GREKF11-02 to Ou., GREKF12-04 to Bi., GREKF13-04 to T.W. and GREKF10-02 to C.C.), and the Natural Science Foundation of Yunnan Province (2009CD107 and 2010CI044 to H.S.). |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000321820400014 |
| 公开日期 | 2013-08-30 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7618]  |
| 专题 | 昆明动物研究所_比较基因组学 昆明动物研究所_遗传资源与进化国家重点实验室 昆明动物研究所_转化基因组 |
| 作者单位 | 1.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 2.University of Chinese Academy of Sciences, Beijing, China 3.High Altitude Medical Research Center, School of Medicine, Tibetan University, Lhasa, China 4.People’s Hospital of Dangxiong County, Dangxiong, China 5.National Key Laboratory of High Altitude Medicine, High Altitude Medical Research Institute, Xining, China 6.Department of Epidemiology and Biostatistics, Harvard School of Public Health |
| 推荐引用方式 GB/T 7714 | Xiang K,Ouzhuluobu,Peng Y,et al. Identification of a Tibetan-Specific Mutation in the Hypoxic Gene EGLN1 and Its Contribution to High-Altitude Adaptation[J]. MOLECULAR BIOLOGY AND EVOLUTION,2013,30(8):1889-1898. |
| APA | Xiang K.,Ouzhuluobu.,Peng Y.,Yang ZH.,Zhang XM.,...&Su B[*].(2013).Identification of a Tibetan-Specific Mutation in the Hypoxic Gene EGLN1 and Its Contribution to High-Altitude Adaptation.MOLECULAR BIOLOGY AND EVOLUTION,30(8),1889-1898. |
| MLA | Xiang K,et al."Identification of a Tibetan-Specific Mutation in the Hypoxic Gene EGLN1 and Its Contribution to High-Altitude Adaptation".MOLECULAR BIOLOGY AND EVOLUTION 30.8(2013):1889-1898. |
入库方式： OAI收割
来源：昆明动物研究所
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