EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production.
EP300 contributes to high-altitude adaptation in Tibetans by regulating nitric oxide production.
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EP300通过调节一氧化氮的产生促进藏族人的高海拔适应
DOI：
10.24272/j.issn.2095-8137.2017.036
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发表时间：
2017-05-18
影响因子：
4.9
通讯作者：
Su B
中科院分区：
文献类型：
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作者：
Zheng WS;He YX;Cui CY;Ouzhu L;Deji Q;Peng Y;Bai CJ;Duoji Z;Gongga L;Bian B;Baima K;Pan YY;Qu L;Kang M;Ciren Y;Baima Y;Guo W;Yang L;Zhang H;Zhang XM;Guo YB;Xu SH;Chen H;Zhao SG;Cai Y;Liu SM;Wu TY;Qi XB;Su B
如较早的研究所表明的那样，藏族对高海拔缺氧的遗传适应可能涉及缺氧途径中的一组基因。为了测试先前报道的候选基因EP300（组蛋白乙酰转移酶P300）的适应性作用，我们在80个无关的藏族中进行了108.9 kb基因区域的EP300的重新配置。等位基因频率和基于单倍型的中性测试检测到藏族在EP300上选择阳性的信号，其中一组变体显示了藏族和低地参考人群之间的等位基因差异，包括汉族中国，欧洲人和非洲人。功能预测表明，多个EP300变体参与基因表达调节。更重要的是，226个藏族的遗传关联检测表明，自适应EP300变体与血液一氧化氮（NO）浓度显着相关。总的来说，我们建议藏族中的EP300具有自适应变体，这可能会通过调节无生产来有助于高空适应。
The genetic adaptation of Tibetans to high altitude hypoxia likely involves a group of genes in the hypoxic pathway, as suggested by earlier studies. To test the adaptive role of the previously reported candidate gene EP300 (histone acetyltransferase p300), we conducted resequencing of a 108.9 kb gene region of EP300 in 80 unrelated Tibetans. The allele-frequency and haplotype-based neutrality tests detected signals of positive Darwinian selection on EP300 in Tibetans, with a group of variants showing allelic divergence between Tibetans and lowland reference populations, including Han Chinese, Europeans, and Africans. Functional prediction suggested the involvement of multiple EP300 variants in gene expression regulation. More importantly, genetic association tests in 226 Tibetans indicated significant correlation of the adaptive EP300 variants with blood nitric oxide (NO) concentration. Collectively, we propose that EP300 harbors adaptive variants in Tibetans, which might contribute to high-altitude adaptation through regulating NO production.