现代人大约10万年前走出非洲并扩散到世界各地，他们在史前迁徙的过程中会面临新环境的生存挑战。世袭在青藏高原的藏民族对高原缺氧的环境具有很好的适应力，但其适应的遗传机制长期以来一直是未解之谜。
宿兵研究员课题组（博士生彭忆、杨召辉，研实员张慧和副研究员石宏等）和西藏大学以及美国哈佛医学院的科研人员合作，对藏族高海拔适应性的遗传学机制开展了系统的研究。经过全基因组单核苷酸序列多态（SNP）芯片扫描，他们发现EPAS1 和 EGLN1这两个低氧相关基因在藏族人群中有很强的自然选择信号，且与汉族在单倍型频率上表现出很大的差异。通过对EPAS1基因的全测序分析，发现这个基因在藏族人群中发生了很强的自然选择，选择时间大约至少1.8万年以上。这一结果从分子水平初步揭示了藏族高原适应的遗传学机制。研究结果发表于国际知名刊物Molecular Biology and Evolution。
推荐英文摘要：
Mol Biol Evol doi: 10.1093/molbev/msq290
Genetic variations in Tibetan populations and high altitude adaptation at the Himalayas
Yi Peng1,6,7, Zhaohui Yang1,6,7, Hui Zhang1,7, Chaoying Cui2,7, Xuebin Qi1, Xiongjian Luo1, Xiang Tao3, Tianyi Wu3, Ouzhuluobu2, Basang4, Ciwangsangbu4, Danzengduojie4, Hua Chen5, Hong Shi1,* and Bing Su1,*
1State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology and Kunming Primate Research Center, Chinese Academy of Sciences, Kunming 650223, China
2School of Medicine, Tibetan University, Lhasa 850000, China
3National Key Laboratory of High Altitude Medicine, High Altitude Medical Research Institute, Xining 810012, China
4People's Hospital of Dangxiong County, Dangxiong 851500, China
5Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
6Graduate School of Chinese Academy Sciences, Beijing 100101, China
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 UV 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.
