Eichstaedt Christina A, Antão Tiago, Pagani Luca, Cardona Alexia, Kivisild Toomas, Mormina Maru
Division of Biological Anthropology, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom.
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom.
PLoS One. 2014 Mar 31;9(3):e93314. doi: 10.1371/journal.pone.0093314. eCollection 2014.
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.
在人类从非洲迁徙出来的过程中，他们成功地在各种栖息地定居并适应了这些环境，包括极端的高海拔环境，在那里大气氧含量降低（低氧）带来了许多生理挑战。本研究评估了生活在阿根廷安第斯山脉海拔3500米以上的科利亚人群的遗传和表型变异，并将其与附近低地的维奇人群进行比较，以确定适应高海拔低氧的潜在进化机制。我们对每个群体的25名个体中的730,525个单核苷酸多态性（SNP）进行了基因分型。在全基因组扩展单倍型纯合性扫描中，科利亚人群在血管内皮生长因子B（VEGFB，在缺血性心脏中起重要作用）和ELTD1（另一个对心脏发育和预防心脏肥大至关重要的基因）周围显示出最强的信号。此外，通路富集分析表明与心脏形态相关的通路显著富集。综上所述，这些发现表明科利亚高地人可能已经进化出一套适应性机制，导致心脏强化，最有可能是为了抵消永久性增加的血细胞比容和相关剪切力的不利影响，这些是安第斯山脉对低氧反应的特征。脑血管流量的调节似乎也是科利亚人群适应性反应的一部分。这些发现不仅与理解高海拔人群低氧保护的进化有关，还可能为低氧构成有害因素的疾病的医学研究提供新的途径。
