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Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders

文献类型：期刊论文

作者Deng, Lian1; Zhang, Chao1; Yuan, Kai1; Gao, Yang1; Pan, Yuwen1; Ge, Xueling1; Yuan, Yuan1; Lu, Yan1; Zhang, Xiaoxi1,2; Chen, Hao1
刊名NATIONAL SCIENCE REVIEW
出版日期2019
卷号6期号:6页码:1201-1222
关键词Tibetan adaptive genetic variant high-altitude adaptation next-generation sequencing (NGS) archaic ancestry expression quantitative traits loci (eQTL) tissue-specific expression hemoglobin concentration hypoxia
ISSN号2095-5138
DOI10.1093/nsr/nwz108
文献子类Article
英文摘要Human genetic adaptation to high altitudes (>2500 m) has been extensively studied over the last few years, but few functional adaptive genetic variants have been identified, largely owing to the lack of deep-genome sequencing data available to previous studies. Here, we build a list of putative adaptive variants, including 63 missense, 7 loss-of-function, 1,298 evolutionarily conserved variants and 509 expression quantitative traits loci. Notably, the top signal of selection is located in TMEM247, a transmembrane protein-coding gene. The Tibetan version of TMEM247 harbors one high-frequency (76.3%) missense variant, rs116983452 (c.248C > T; p.Ala83Val), with the T allele derived from archaic ancestry and carried by >94% of Tibetans but absent or in low frequencies (<3%) in non-Tibetan populations. The rs116983452-T is strongly and positively correlated with altitude and significantly associated with reduced hemoglobin concentration (p = 5.78 x 10(-5)), red blood cell count (p = 5.72 x 10(-7)) and hematocrit (p = 2.57 x 10(-6)). In particular, TMEM247-rs116983452 shows greater effect size and better predicts the phenotypic outcome than any EPAS1 variants in association with adaptive traits in Tibetans. Modeling the interaction between TMEM247-rs116983452 and EPAS1 variants indicates weak but statistically significant epistatic effects. Our results support that multiple variants may jointly deliver the fitness of the Tibetans on the plateau, where a complex model is needed to elucidate the adaptive evolution mechanism.
学科主题Biochemistry & Molecular Biology
WOS关键词HIGH-ALTITUDE ADAPTATION ; POSITIVE SELECTION ; EXPRESSION ; HYPOXIA ; NEANDERTHAL ; IDENTIFICATION ; INTROGRESSION ; ASSOCIATION ; FRAMEWORK ; HAPLOTYPE
语种英语
WOS记录号WOS:000512970300030
出版者OXFORD UNIV PRESS
版本出版稿
源URL[http://202.127.25.144/handle/331004/824]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci,Shanghai Inst Nutr & Hlth, Univ Chinese Acad Sci,Key Lab Computat Biol, Shanghai 200031, Peoples R China;
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China;
3.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China;
4.Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China;
5.Fudan Univ, Sch Life Sci, Key Lab Contemporary Anthropol, Minist Educ MOE, Shanghai 200433, Peoples R China;
6.Wenzhou Med Univ, Sch Ophthalmol & Optometry, Hosp Eye, Wenzhou, Peoples R China;
7.Natl Ctr Int Res Regenerat Med & Neurogenet, State Key Lab Ophthalmol Optometry & Visual Sci, Wenzhou 325027, Peoples R China;
8.Univ Queensland, Inst Mol Biosci, Queensland Brain Inst, Brisbane, Qld 4072, Australia;
9.Xizang Minzu Univ, Sch Med, Key Lab Mol Genet Mech & Intervent Res High Altit, Xianyang 712082, Peoples R China;
10.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China;
推荐引用方式
GB/T 7714		 Deng, Lian,Zhang, Chao,Yuan, Kai,et al. Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders[J]. NATIONAL SCIENCE REVIEW,2019,6(6):1201-1222.
APA Deng, Lian.,Zhang, Chao.,Yuan, Kai.,Gao, Yang.,Pan, Yuwen.,...&,.(2019).Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders.NATIONAL SCIENCE REVIEW,6(6),1201-1222.
MLA Deng, Lian,et al."Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders".NATIONAL SCIENCE REVIEW 6.6(2019):1201-1222.

入库方式： OAI收割

来源：上海营养与健康研究所

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