Genetic Variations in Tibetan Populations and High-Altitude Adaptation at the Himalayas
Genetic Variations in Tibetan Populations and High-Altitude Adaptation at the Himalayas
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DOI：
10.1093/molbev/msq290
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发表时间：
2011-02-01
影响因子：
10.7
通讯作者：
Su, Bing
中科院分区：
文献类型：
--
作者：
Peng, Yi;Yang, Zhaohui;Su, Bing
自从大约10万年前离开非洲以来，现代人类几乎占据了全球所有可能的环境。行为和生物适应都有助于他们成功地在极端气候条件下生存下来，包括寒冷，强紫外线辐射和高海拔。在这些环境压力中，高海拔缺氧是传统技术无法调解其影响的唯一条件。居住在海拔3,000米以上的高原上的藏族人口提供了一个被广泛研究的高海拔适应的例子。然而，在这种极端环境中长期生存的遗传机制仍然未知。我们对藏族人的全基因组序列变异进行了分析。结合已报道的数据，我们在两个缺氧相关基因EPAS 1和EGLN 1中发现了选择性扫描的强信号。对于这两个基因，藏族人显示出与非藏族低地人（汉族人和日本人）异常高的差异，并具有高频率的许多连锁序列变异，这反映了藏族特有的单倍型。对7个藏人群体（1,334人）的进一步分析表明，喜马拉雅地区普遍存在选择性横扫。EPAS 1和EGLN 1上的自然选择指标表明，在长期的高海拔地区生活过程中，藏族人群中获得生物适应高原低氧的功能序列变异得到了丰富。
Modern humans have occupied almost all possible environments globally since exiting Africa about 100,000 years ago. Both behavioral and biological adaptations have contributed to their success in surviving the rigors of climatic extremes, including cold, strong ultraviolet radiation, and high altitude. Among these environmental stresses, high-altitude hypoxia is the only condition in which traditional technology is incapable of mediating its effects. Inhabiting at >3,000-m high plateau, the Tibetan population provides a widely studied example of high-altitude adaptation. Yet, the genetic mechanisms underpinning long-term survival in this environmental extreme remain unknown. We performed an analysis of genome-wide sequence variations in Tibetans. In combination with the reported data, we identified strong signals of selective sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han Chinese and Japanese) and possess high frequencies of many linked sequence variations as reflected by the Tibetan-specific haplotypes. Further analysis in seven Tibetan populations (1,334 individuals) indicates the prevalence of selective sweep across the Himalayan region. The observed indicators of natural selection on EPAS1 and EGLN1 suggest that during the long-term occupation of high-altitude areas, the functional sequence variations for acquiring biological adaptation to high-altitude hypoxia have been enriched in Tibetan populations.