Evidence of Polygenic Adaptation to High Altitude from Tibetan and Sherpa Genomes.
Evidence of Polygenic Adaptation to High Altitude from Tibetan and Sherpa Genomes.
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藏族和夏尔巴人基因组多基因适应高海拔的证据。
DOI：
10.1093/gbe/evy233
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发表时间：
2018-11-01
影响因子：
3.3
通讯作者：
Sazzini M
中科院分区：
文献类型：
--
作者：
Gnecchi-Ruscone GA;Abondio P;De Fanti S;Sarno S;Sherpa MG;Sherpa PT;Marinelli G;Natali L;Di Marcello M;Peluzzi D;Luiselli D;Pettener D;Sazzini M
尽管藏族人和夏尔巴人为了应对高海拔环境，特别是低压低氧带来的选择压力而进化出了几种生理调节，但在有限数量的低氧相关基因上，很少有选择性扫描被多个基因组研究证实。然而，这些基因座的变异被发现只与红系造血级联反应的下调有关，这代表了被认为的适应性表型的一个间接方面。因此，藏族/夏尔巴族适应性性状的遗传基础仍有待充分阐明，部分原因是迄今实施的选择扫描的局限性，而且主要依赖于硬扫描模型。为了克服这个问题，我们使用全基因组序列数据和几个选择统计作为输入进行基因网络分析，目的是测试这些高海拔喜马拉雅种群是否发生多基因适应。这种方法还能够检测到微妙的基因组特征，归因于同一功能子网络的多个基因的弱正选择，使我们能够在单独显示小效应大小的基因座上推断适应性进化，但属于高度相互关联的生物路径，总体上涉及血管生成过程。因此，这些发现准确地指出了迄今为止被忽视的一系列选择性事件，这些事件可能导致在藏族和夏尔巴人中观察到的组织血液灌注量增加，从而揭示了他们适应高海拔的关键生物学机制的遗传决定因素。
Although Tibetans and Sherpa present several physiological adjustments evolved to cope with selective pressures imposed by the high-altitude environment, especially hypobaric hypoxia, few selective sweeps at a limited number of hypoxia related genes were confirmed by multiple genomic studies. Nevertheless, variants at these loci were found to be associated only with downregulation of the erythropoietic cascade, which represents an indirect aspect of the considered adaptive phenotype. Accordingly, the genetic basis of Tibetan/Sherpa adaptive traits remains to be fully elucidated, in part due to limitations of selection scans implemented so far and mostly relying on the hard sweep model. In order to overcome this issue, we used whole-genome sequence data and several selection statistics as input for gene network analyses aimed at testing for the occurrence of polygenic adaptation in these high-altitude Himalayan populations. Being able to detect also subtle genomic signatures ascribable to weak positive selection at multiple genes of the same functional subnetwork, this approach allowed us to infer adaptive evolution at loci individually showing small effect sizes, but belonging to highly interconnected biological pathways overall involved in angiogenetic processes. Therefore, these findings pinpointed a series of selective events neglected so far, which likely contributed to the augmented tissue blood perfusion observed in Tibetans and Sherpa, thus uncovering the genetic determinants of a key biological mechanism that underlies their adaptation to high altitude.
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影响因子：
4
作者：
Jeong, Choongwon;Di Rienzo, Anna
通讯作者：
Di Rienzo, Anna
影响因子：
3.3
作者：
Jansen, Gerard F. A.;Krins, Anne;Ince, Can
通讯作者：
Ince, Can
影响因子：
4.1
作者：
Abhinand, Chandran S.;Raju, Rajesh;Sudhakaran, Perumana R.
通讯作者：
Sudhakaran, Perumana R.
影响因子：
8.4
作者：
Gilbert-Kawai, Edward T.;Milledge, James S.;Martin, Daniel S.
通讯作者：
Martin, Daniel S.
DOI：
10.1073/pnas.1002443107
发表时间：
2010-06-22
影响因子：
11.1
作者：
Beall, Cynthia M.;Cavalleri, Gianpiero L.;Zheng, Yong Tang
通讯作者：
Zheng, Yong Tang