Genetic adaptation of skin pigmentation in highland Tibetans

• DOI: 10.1073/pnas.2200421119
• Publication Date: 2022-09-26T19:21:09Z
• Authors: Zhaohui Yang; Caijuan Bai; Youwei Pu; Qinghong Kong; Yongbo Guo; ; ; Xuyang Liu; Qi Zhao; Zhichao Qiu; Wangshan Zheng; Yaoxi He; Yihan Lin; Lian Deng; Chao Zhang; Shuhua Xu; Yi Peng; Kun Xiang; Xiaoming Zhang; ; ; Chaoying Cui; ; ; ; Yongyue Pan; Jingxue Xin; Yong Wang; Shiming Liu; Liangbang Wang; Hengliang Guo; Zhenzhen Feng; Shaobo Wang; Hong Shi; Binghua Jiang; Tianyi Wu; Xuebin Qi; Bing Su
• Keywords: Dark skin

Strong ultraviolet (UV) radiation at high altitude imposes a serious selective pressure, which may induce skin pigmentation adaptation of indigenous populations. We conducted phenotyping and genome-wide analysis Tibetans in order to understand the underlying mechanism UV radiation. observe that have darker baseline color compared with lowland Han Chinese, as well an improved tanning ability, suggesting two-level boost their melanin production. A search for responsible genes identifies GNPAT showing strong signals positive selection Tibetans. An enhancer mutation (rs75356281) located intron 2 is enriched (58%) but rare other world populations (0 18%). The adaptive allele rs75356281 associated and, under UVB treatment, it displays higher activities wild-type vitro luciferase assays. Transcriptome analyses gene-edited cells clearly show variant promotes synthesis, likely through interactions CAT ACAA1 peroxisomes genes, they act synergistically, leading ability protection.