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非洲和非非洲人群之间人类锌转运蛋白基因的差异自然选择

Differential Natural Selection of Human Zinc Transporter Genes between African and Non-African Populations.

作者信息

Zhang Chao, Li Jing, Tian Lei, Lu Dongsheng, Yuan Kai, Yuan Yuan, Xu Shuhua

机构信息

Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

1] Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China [2] School of Life Science and Technology, ShanghaiTec University, Shanghai 200031, China [3] Collaborative Innovation Center of Genetics and Development, Shanghai 200438, China.

出版信息

Sci Rep. 2015 Apr 30;5:9658. doi: 10.1038/srep09658.

Abstract

Zinc transporters play important roles in all eukaryotes by maintaining the rational zinc concentration in cells. However, the diversity of zinc transporter genes (ZTGs) remains poorly studied. Here, we investigated the genetic diversity of 24 human ZTGs based on the 1000 Genomes data. Some ZTGs show small population differences, such as SLC30A6 with a weighted-average FST (WA-FST = 0.015), while other ZTGs exhibit considerably large population differences, such as SLC30A9 (WA-FST = 0.284). Overall, ZTGs harbor many more highly population-differentiated variants compared with random genes. Intriguingly, we found that SLC30A9 was underlying natural selection in both East Asians (EAS) and Africans (AFR) but in different directions. Notably, a non-synonymous variant (rs1047626) in SLC30A9 is almost fixed with 96.4% A in EAS and 92% G in AFR, respectively. Consequently, there are two different functional haplotypes exhibiting dominant abundance in AFR and EAS, respectively. Furthermore, a strong correlation was observed between the haplotype frequencies of SLC30A9 and distributions of zinc contents in soils or crops. We speculate that the genetic differentiation of ZTGs could directly contribute to population heterogeneity in zinc transporting capabilities and local adaptations of human populations in regard to the local zinc state or diets, which have both evolutionary and medical implications.

摘要

锌转运蛋白通过维持细胞内合理的锌浓度在所有真核生物中发挥重要作用。然而,锌转运蛋白基因(ZTGs)的多样性仍研究不足。在此,我们基于千人基因组数据研究了24个人类ZTGs的遗传多样性。一些ZTGs表现出较小的群体差异,如SLC30A6的加权平均FST(WA-FST = 0.015),而其他ZTGs则表现出相当大的群体差异,如SLC30A9(WA-FST = 0.284)。总体而言,与随机基因相比,ZTGs含有更多高度群体分化的变异。有趣的是,我们发现SLC30A9在东亚人(EAS)和非洲人(AFR)中均受到自然选择,但方向不同。值得注意的是,SLC30A9中的一个非同义变异(rs1047626)在EAS中几乎固定为96.4%的A,在AFR中为92%的G。因此,存在两种不同的功能单倍型,分别在AFR和EAS中表现出优势丰度。此外,观察到SLC30A9的单倍型频率与土壤或作物中锌含量的分布之间存在很强的相关性。我们推测,ZTGs的遗传分化可能直接导致人群在锌转运能力方面的异质性以及人类群体对当地锌状态或饮食的局部适应,这具有进化和医学意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec5d/5386188/264cff778916/srep09658-f1.jpg

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