The adaptation of Tibetans to high-altitude environments has been studied extensively. However, the direct assessment of evolutionary adaptation, i.e., the reproductive fitness of Tibetans and its genetic basis, remains elusive. Here, we conduct systematic phenotyping and genome-wide association analysis of 2,252 mother-newborn pairs of indigenous Tibetans, covering 12 reproductive traits and 76 maternal physiological traits. Compared with the lowland immigrants living at high altitudes, indigenous Tibetans show better reproductive outcomes, reflected by their lower abortion rate, higher birth weight, and better fetal development. The results of genome-wide association analyses indicate a polygenic adaptation of reproduction in Tibetans, attributed to the genomic backgrounds of both the mothers and the newborns. Furthermore, the EPAS1-edited mice display higher reproductive fitness under chronic hypoxia, mirroring the situation in Tibetans. Collectively, these results shed new light on the phenotypic pattern and the genetic mechanism of human reproductive fitness in extreme environments.  

　　Publication:  

　　Current Biology, Volume 33, Issue 19, 9 October 2023, Pages 4037-4051.e5  

　　http://dx.doi.org/10.1016/j.cub.2023.08.021  

　　Author:  

　　Yaoxi He  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Yongbo Guo  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China  

　　Wangshan Zheng  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China  

　　Tian Yue  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China  

　　Hui Zhang  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650000, China  

　　Bin Wang  

　　Fukang Obstetrics, Gynecology and Children Branch Hospital, Tibetan Fukang Hospital, Lhasa 850000, China  

　　Zhanying Feng  

　　CEMS, NCMIS, MDIS, Academy of Mathematics & Systems Science, Chinese Academy of Sciences, Beijing 100080, China  

　　Ouzhuluobu  

　　Fukang Obstetrics, Gynecology and Children Branch Hospital, Tibetan Fukang Hospital, Lhasa 850000, China  

　　High Altitude Medical Research Center, School of Medicine, Tibetan University, Lhasa 850000, China  

　　Chaoying Cui  

　　Fukang Obstetrics, Gynecology and Children Branch Hospital, Tibetan Fukang Hospital, Lhasa 850000, China  

　　High Altitude Medical Research Center, School of Medicine, Tibetan University, Lhasa 850000, China  

　　Kai Liu  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Bin Zhou  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China  

　　Xuerui Zeng  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China  

　　Liya Li  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Tianyun Wang Department of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China  

　　Yong Wang  

　　CEMS, NCMIS, MDIS, Academy of Mathematics & Systems Science, Chinese Academy of Sciences, Beijing 100080, China  

　　Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China  

　　Email: ywang@amss.ac.cn  

　　Chao Zhang  

　　Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China  

　　Shuhua Xu  

　　State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China  

　　Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and Ministry of Education Key Laboratory of Contemporary Anthropology, Fudan University, Shanghai 201203, China  

　　Xuebin Qi  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Fukang Obstetrics, Gynecology and Children Branch Hospital, Tibetan Fukang Hospital, Lhasa 850000, China  

　　State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650000, China  

　　Bing Su  

　　State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China  

　　Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China