Natural selection and genes determining higher arterial saturation in Peruvian Quechua

在世界范围内，一些人可能已经适应了基于长期居住在3000米以上山区的高海拔(HA)。在南美洲的安第斯地区，至少在过去的6000年里，盖丘亚人一直生活在平均海拔4000米的地方。该项目的具体目标将是收集克丘亚人(n=600)的遗传和生理特征数据，并测试先前确定的遗传标记与高动脉血氧饱和度(SaO2)之间的关联。该项目的结果可能会为安第斯山脉人口是否在基因上适应高海拔这一长期存在的问题提供答案。盖丘亚州的样本将包括在HA或海平面上出生和长大的亚样本。这将允许评估发育影响，因为这些也可能决定更高的SaO2。随机抽取300名低地居民作为对照组。对于房委会的盖丘亚人居住地来说，6000年是一个保守的时间深度估计，足以让盖丘亚人经历自然选择，即遗传适应。选择可能有利于在长期低氧气水平的挑战下存活的性状，例如与氧气运输能力有关的性状。除了遗传外，HA的生长和发育可能表现出发育适应。例如，在医管局出生和长大的人的肺大小会增加。目前的项目将测试遗传和发育假说，以解释秘鲁盖丘亚人的SaO2。血氧饱和度是决定血液中含氧量的主要因素，而盖丘亚在HA运动期间保持高血氧饱和度方面尤其令人印象深刻。在之前的工作中，目前的研究团队使用全基因组方法来识别盖丘亚语的基因组区域，这表明了自然选择的先验证据。这项基因组扫描使用了一组密集的单核苷酸多态(SNP)遗传标记，并提供了缺氧诱导因子(HIF)途径中几个基因的自然选择的证据。HIF是一种中央调控因子，控制与维持细胞氧气水平有关的下游基因。该项目是与秘鲁研究人员的国际合作，包括美国和秘鲁的学生参与。

Worldwide, several human populations may have adapted to high altitude (HA) based on long-term residence in mountainous areas above 3,000 meters. In the Andean region of South America, Quechua natives have lived at altitudes averaging 4,000 meters for at least the past 6,000 years. The specific aim of this project will be to collect genetic and physiological trait data on Quechua (n=600) and to test for association between previously identified genetic markers and high arterial hemoglobin-oxygen saturation (SaO2). The results of this project could provide an answer to the long-standing question of whether Andean populations are genetically adapted to high altitude. The Quechua sample will include sub-samples, born and raised at HA or at sea-level. This will allow evaluation of developmental effects as these may also determine higher SaO2. A sample of n=300 lowlanders will serve as a control group. Six thousand years is a conservative time-depth estimate for Quechua residence at HA and is long enough for Quechua to have experienced natural selection i.e., genetic adaptation. Selection could have favored traits enabling survival under the challenge of chronically low oxygen levels, such as traits related to O2 transport capacity. Apart from genetics, growth and development at HA may exhibit developmental adaptation. For example, lung-size is enhanced in persons born and raised at HA. The current project will test both genetic and developmental hypotheses to explain SaO2 of Peruvian Quechua. The SaO2 is a major determinant of the amount of oxygen in the blood, and Quechua are especially impressive in maintaining high SaO2 during exercise at HA. In previous work, the current research team used a whole-genome approach to identify genomic regions in Quechua that showed strong a priori evidence of natural selection. This genome scan used a dense panel of single nucleotide polymorphism (SNP) genetic markers, and provided evidence of natural selection in several genes of the hypoxia inducible factor (HIF) pathway. HIF is a central regulator that controls downstream genes involved in maintaining cellular oxygen levels.The project is an international collaboration with Peruvian researchers and includes student involvement in both the USA and Peru.