Deep phenotyping of 11,880 highlanders reveals novel adaptive traits in native Tibetans

Yaoxi He; Wangshan Zheng; Yongbo Guo; Tian Yue; Chaoying Cui; Ouzhuluobu; Hui Zhang; Kai Liu; Zhaohui Yang; Tianyi Wu; Jia Qu; Zi-Bing Jin; Jian Yang; Fan Lu; Xuebin Qi; Bing Su

doi:10.1016/j.isci.2023.107677

Deep phenotyping of 11,880 highlanders reveals novel adaptive traits in native Tibetans

iScience. 2023 Aug 18;26(9):107677. doi: 10.1016/j.isci.2023.107677. eCollection 2023 Sep 15.

Authors

Yaoxi He¹, Wangshan Zheng^{1

2}, Yongbo Guo^{1

2}, Tian Yue^{1

2}, Chaoying Cui³, Ouzhuluobu³, Hui Zhang^{1

4}, Kai Liu^{1

2}, Zhaohui Yang^{1

5}, Tianyi Wu⁶, Jia Qu⁷, Zi-Bing Jin^{7

8}, Jian Yang^{9

10}, Fan Lu⁷, Xuebin Qi^{1

3

4}, Bing Su^{1

11}

Affiliations

¹ State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
² Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100101, China.
³ Tibetan Fukang Hospital, Lhasa 850000, China.
⁴ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650000, China.
⁵ Academy of Medicine Science, Zhengzhou University, Zhengzhou 450052, China.
⁶ National Key Laboratory of High Altitude Medicine, High Altitude Medical Research Institute, Xining 810012, China.
⁷ Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.
⁸ Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing 100730, China.
⁹ School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China.
¹⁰ Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China.
¹¹ Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China.

Abstract

Tibetans are the ideal population to study genetic adaptation in extreme environments. Here, we performed systematic phenotyping of 11,880 highlanders, covering 133 quantitative traits of 13 organ systems. We provided a comprehensive phenotypic atlas by comparing altitude adaptation and altitude acclimatization. We found the differences between adaptation and acclimatization are quantitative rather than qualitative, with a whole-system "blunted effect" seen in the adapted Tibetans. We characterized twelve different functional changes between adaptation and acclimatization. More importantly, we established a landscape of adaptive phenotypes of indigenous Tibetans, including 45 newly identified Tibetan adaptation-nominated traits, involving specific changes of Tibetans in internal organ state, metabolism, eye morphology, and skin pigmentation. In addition, we observed a sex-biased pattern between altitude acclimatization and adaptation. The generated atlas of phenotypic landscape provides new insights into understanding of human adaptation to high-altitude environments, and it serves as a valuable blueprint for future medical and physiological studies.

Keywords: Anthropology; Human physiology; Physiology.