Natural selection and genes determining higher arterial saturation in Peruvian Quechua

在世界范围内，一些人类群体可能已经适应了高海拔（HA），这是基于长期居住在3,000米以上的山区。在南美洲的安第斯地区，盖丘亚土著人在过去至少6,000年里一直生活在平均海拔4,000米的地方。该项目的具体目标是收集克丘亚语（n=600）的遗传和生理性状数据，并测试先前确定的遗传标记和高动脉血红蛋白血氧饱和度（SaO 2）之间的关联。这个项目的结果可以为安第斯人是否在遗传上适应高海拔这一长期存在的问题提供答案。克丘亚族样本将包括在HA或海平面出生和长大的子样本。这将允许对发育影响进行评价，因为这些影响也可能决定较高的SaO 2。将n=300名低地人作为对照组。6000年是盖丘亚人在HA居住的保守时间深度估计，对于盖丘亚人来说足够长，可以经历自然选择，即，遗传适应选择可能有利于在长期低氧水平的挑战下生存的性状，例如与O2运输能力相关的性状。除了遗传学，HA的生长和发育可能表现出发育适应性。例如，在HA出生和长大的人的肺大小增加。目前的项目将测试遗传和发育假设，以解释秘鲁克丘亚人的SaO 2。血氧饱和度是血液中含氧量的主要决定因素，盖丘亚语在HA运动期间保持高血氧饱和度尤其令人印象深刻。在以前的工作中，目前的研究小组使用全基因组方法来确定克丘亚语中的基因组区域，这些区域显示出强有力的自然选择先验证据。该基因组扫描使用了一组密集的单核苷酸多态性（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证据。HIF是一种控制下游基因的中心调节因子，这些基因参与维持细胞氧水平。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.