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

KIZ OpenIR > 科研部门 > 比较基因组学（宿兵）

	Prioritizing natural-selection signals from the deep-sequencing genomic data suggests multi-variant adaptation in Tibetan highlanders
	Deng, L; Zhang, C; Yuan, K; Gao, Y; Pan, YW; Ge, XL; He, YX; Yuan, Y; Lu, Y; Zhang, XX; Chen, H; Lou, HY; Wang, XJ; Lu, DS; Liu, JJ; Tian, L; Feng, QD; Khan, A; Yang, YJ; Jin, ZB; Yang, J; Lu, F; Qu, J; Kang, LL; Su, B; Xu, SH
	2019
发表期刊	NATIONAL SCIENCE REVIEW
ISSN	2095-5138
卷号	6 期号:6 页码:1201-1222
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.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13542
专题	科研部门_比较基因组学（宿兵）
推荐引用方式 GB/T 7714	Deng, L,Zhang, C,Yuan, K,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, L.,Zhang, C.,Yuan, K.,Gao, Y.,Pan, YW.,...&Xu, SH.(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, L,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.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2023030818.pdf（3588KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文