Fitness and Function of Oxygen Saturation Genotypes in Tibet

人类生活在各种各样的环境中。当然，这些环境中最具挑战性的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在这些地区逗留期间是否从生物学上适应了氧气压力降低的压力，已经引起了相当大的科学兴趣。虽然许多先前的研究已经评估了生活在高海拔地区的种群的生物变异和适应性，但这些群体是否具有对高海拔压力的遗传适应性的问题已经证明是难以解决的。最近的研究表明，在中国自治区居住在海拔4000米以上村庄的藏族人口中，一个单一的主要基因可能会提高携带者动脉血红蛋白的氧饱和度。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氧饱和度，而且具有更强的生殖适应性。本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妇女，如果拥有至少一份假定的高氧饱和度基因，也会比那些没有高氧饱和度基因的妇女表现出更高的生殖率。该项目还将验证生活在不同高海拔地区的藏族人群更好地适应氧运输、免疫和内分泌系统功能整合的假设。这项研究扩大了对高海拔氧气运输的关注，以测量在人口统计学和生物学结果方面，受遗传影响的生理反应变异对低氧压的影响。它将首次详细介绍生活在缺氧应激下的人从青春期到老年的免疫、内分泌和心肺系统及其整合情况。该研究还通过使用定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其潜在的遗传决定因素并正式测试其与适应度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.