The Andean adaptive toolkit to counteract high altitude maladaptation: genome-wide and phenotypic analysis of the Collas.
The Andean adaptive toolkit to counteract high altitude maladaptation: genome-wide and phenotypic analysis of the Collas.
复制标题
DOI：
10.1371/journal.pone.0093314
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Mormina M
中科院分区：
文献类型：
--
作者：
Eichstaedt CA;Antão T;Pagani L;Cardona A;Kivisild T;Mormina M
在迁出非洲的过程中，人类成功地殖民和适应了广泛的生境，包括极端高海拔环境，在那里大气氧气减少(缺氧)会带来许多生理挑战。这项研究评估了生活在海拔3500米以上阿根廷安第斯山脉的科拉种群的遗传和表型变异，并将其与附近的低地威西种群进行比较，试图查明适应高海拔低氧的进化机制。我们对来自每个群体的25个个体的730,525个SNPs进行了基因分型。在扩展的单倍型纯合性的全基因组扫描中，COLAS显示在VEGFB和ELTD1附近的信号最强，VEGFB在缺血心脏中起着关键作用，ELTD1是另一个对心脏发育和预防心肌肥大至关重要的基因。此外，通路富集化分析显示与心脏形态相关的通路过度表达。综上所述，这些发现表明，Colla Highlanders可能进化出了一套适应机制，导致心脏强化，最有可能抵消永久增加的红细胞压积和相关剪切力的不利影响，这些影响是安第斯山脉对缺氧的反应的特征。脑血管血流的调节似乎也是COLAS适应性反应的一部分。这些发现不仅与了解高海拔人群低氧保护的演变有关，还可能为低氧构成有害因素的条件的医学研究提供新的途径。
During their migrations out of Africa, humans successfully colonised and adapted to a wide range of habitats, including extreme high altitude environments, where reduced atmospheric oxygen (hypoxia) imposes a number of physiological challenges. This study evaluates genetic and phenotypic variation in the Colla population living in the Argentinean Andes above 3500 m and compares it to the nearby lowland Wichí group in an attempt to pinpoint evolutionary mechanisms underlying adaptation to high altitude hypoxia. We genotyped 730,525 SNPs in 25 individuals from each population. In genome-wide scans of extended haplotype homozygosity Collas showed the strongest signal around VEGFB, which plays an essential role in the ischemic heart, and ELTD1, another gene crucial for heart development and prevention of cardiac hypertrophy. Moreover, pathway enrichment analysis showed an overrepresentation of pathways associated with cardiac morphology. Taken together, these findings suggest that Colla highlanders may have evolved a toolkit of adaptative mechanisms resulting in cardiac reinforcement, most likely to counteract the adverse effects of the permanently increased haematocrit and associated shear forces that characterise the Andean response to hypoxia. Regulation of cerebral vascular flow also appears to be part of the adaptive response in Collas. These findings are not only relevant to understand the evolution of hypoxia protection in high altitude populations but may also suggest new avenues for medical research into conditions where hypoxia constitutes a detrimental factor.
登录
查看更多内容
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
影响因子：
2.6
作者：
Beall, CM
通讯作者：
Beall, CM
影响因子：
4.5
作者：
Bigham A;Bauchet M;Pinto D;Mao X;Akey JM;Mei R;Scherer SW;Julian CG;Wilson MJ;López Herráez D;Brutsaert T;Parra EJ;Moore LG;Shriver MD
通讯作者：
Shriver MD
影响因子：
4.5
作者：
Alkorta-Aranburu G;Beall CM;Witonsky DB;Gebremedhin A;Pritchard JK;Di Rienzo A
通讯作者：
Di Rienzo A
影响因子：
3
作者：
Alexander DH;Lange K
通讯作者：
Lange K