Fitness and Function of Oxygen Saturation Genotypes in Tibet

人类居住在各种各样的环境中。 当然，这些环境中最具挑战性的环境之一是世界最高山脉的高海拔地区。确定长期居住在这些高海拔地区的人群在这些地区逗留期间是否能够从生物学上适应氧压降低的压力，具有相当大的科学意义。 虽然之前的许多研究已经评估了生活在高海拔地区的人群的生物变异和适应，但这些人群是否具有对海拔压力的遗传适应特征的问题已被证明很难解决。 最近的研究表明，在居住在海拔4000m以上村庄的中国自治区藏族人群中，单个主基因可能具有提高携带者动脉血红蛋白氧饱和度的作用。 此外，初步数据还表明，拥有该基因的个体不仅表现出更高的血氧饱和度，而且具有更高的生殖适应性。该研究项目旨在检验以下假设：来自高海拔地区的藏族女性，如果拥有至少一个假定的高氧饱和度基因，也比不拥有该基因的女性表现出更高的繁殖率。 该项目还将测试生活在不同高海拔地区的藏族人群氧运输、免疫和内分泌系统功能更好的适应性整合的假设。 这项研究扩大了对高海拔氧气输送的关注，以测量受遗传影响的生理反应变化对人口和生物学结果对氧压降低的影响。 它将提供生活在低氧压力下的人们从青春期到老年的免疫、内分泌和心肺系统及其整合的第一个详细概况。 拟议的研究还通过使用定量适应性特征的形式分析模型拓宽了人类遗传适应的研究。 统计遗传分析技术的应用通过分解其潜在的遗传决定因素并正式测试其与适应性和功能的关联来分析假设的适应性特征。

Human populations inhabit a broad range of environments. Certainly one of the most challenging of these environments is the high altitude region of the world's highest mountain ranges. It has been of considerable scientific interest to determine if populations long residing at these high altitudes have accommodated the stress of reduced oxygen pressure biologically during their sojourn in these regions. While many previous studies have evaluated the biological variation and adaptation of populations living at high altitude, the question of whether these groups are characterizied by genetic adaptations to the stresses of altitude has proven difficult to resolve. Recent research indicates that among the Tibetan population of the Autonomous Region of China residing in villages above 4,000m, a single major gene may act to enhance oxygen saturation of arterial hemoglobin in carriers. Moreover, preliminary data also suggest that individuals possessing this gene not only exhibit greater oxygen saturation of blood, but are characterized by greater reproductive fitness. This research project is aimed at testing the hypothesis that Tibetan women from high altitude populations who possess at least one copy of the putative high oxygen saturation gene also exhibit higher reproductive rates than those who do not. The project will also test the hypothesis of better adaptive integration of oxygen transport, immune and endocrine system function in Tibetan populations living at different high altitude elevations. This research expands the focus on oxygen transport at high altitude to measure the consequences of genetically influenced variation in physiological response to lowered oxygen pressure in terms of demographic and biological outcomes. It will provide the first detailed profile of the immune, endocrine, and cardiorespiratory systems and their integration from adolescence through old age among people living under hypoxic stress. The proposed research also broadens the study of human genetic adaptation by using formal analytic models for quantitative adaptive traits. The application of statistical genetic analytical techniques analyzes a hypothetically adaptive trait by decomposing its underlying genetic determinants and formally testing its association with fitness and function.