Fitness and Function of Oxygen Saturation Genotypes in Tibet

人类居住在广泛的环境中。当然，其中最具挑战性的环境之一是世界上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种群是否在生物上适应了在这些地区逗留期间降低的氧压的压力，一直是相当有科学意义的。虽然以前的许多研究评估了生活在高海拔地区的种群的生物多样性和适应能力，但事实证明，这些种群是否具有对海拔压力的遗传适应能力的问题很难解决。最近的研究表明，在海拔4000米以上的中国自治区藏族人口中，可能有一个主基因作用于携带者的动脉血氧饱和度。此外，初步数据还表明，拥有这种基因的个体不仅表现出更高的血液氧饱和度，而且具有更好的生殖适应性。这项研究项目旨在验证这样一种假设，即来自高海拔地区的藏族女性如果至少拥有一份假定的高氧饱和度基因，也会比没有基因的人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口的氧运输、免疫和内分泌系统功能更好地适应整合的假说。这项研究扩大了对高海拔氧气运输的关注，以测量在人口学和生物学结果方面受遗传影响的对较低氧压的生理反应的变化的后果。它将首次提供免疫、内分泌和心肺系统的详细概况，以及从青春期到老年在低氧压力下生活的人中它们的整合。这项研究还通过使用数量适应性状的形式分析模型，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潜在的遗传决定因素来分析假设的适应性特征，并正式测试其与适合度和功能的关联。

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.