Ethiopian Adaptation to High-altitude Hypoxia

现代人类生活在世界上许多地区的高海拔地区，尤其是喜马拉雅山、安第斯山脉和埃塞俄比亚的山脉。研究表明，它们应对在这些海拔高度遇到的压力的生物机制是完全不同的，这生动地证明了人类适应能力的可塑性。该研究的目的是发现埃塞俄比亚独特的适应高海拔模式的机制。这项研究的科学价值在于弄清楚埃塞俄比亚高地居民的血红蛋白氧饱和度和血红蛋白浓度为何明显正常，即使他们生活在高海拔地区，那里每次呼吸的空气中含有的氧分子比海平面低。他们与世界上其他地区的高海拔原住民和高海拔游客形成鲜明对比，他们的血氧饱和度都低于海平面。这项研究的目的是：1)检验两个可供选择的假设，以解释为什么埃塞俄比亚西北高地的土著居民在缺氧胁迫下仍能在正常海平面范围内达到血红蛋白的氧饱和度水平；2)确定埃塞俄比亚遥远的东南高地的居民是否也具有这种高海拔适应模式。第一个目标将通过比较居住在埃塞俄比亚西北部塞米恩山区的阿姆哈拉民族语言群体的85名健康成年人的两个样本来实现，其中一个居住在高海拔（3700-4000米），另一个居住在低海拔（1500米）。有了这些样本，该研究将调查两种可供选择的假设，以解释为什么埃塞俄比亚西北部高地的土著居民在缺氧压力下仍能在正常海平面范围内达到血红蛋白的氧饱和度水平。一种假说认为，埃塞俄比亚高地人能更有效地将周围空气中的氧气转移到动脉血液中；如果血红蛋白的氧饱和度和动脉血的氧分压都在正常海平面范围内，而不是更低，就会得到支持。另一种假说认为，埃塞俄比亚高地人的血红蛋白对氧气的亲和力增加；如果血红蛋白的氧饱和度在正常的海平面范围内，它将得到支持，即使在高海拔地区，动脉血中的氧分压相对较低。拟议研究的第二个目标将通过比较居住在埃塞俄比亚东南部贝尔高原地区的高海拔和低海拔地区的奥罗莫民族语言群体的两个类似样本来实现，这些样本与埃塞俄比亚西北部阿姆哈拉民族语言群体的样本相似。血红蛋白氧饱和度和血红蛋白浓度的测量将证实或否认与西北高地人相似的适应模式。填补埃塞俄比亚适应知识的空白对于理解适应高海拔缺氧的所有可能性以及为开发安第斯人、西藏人和埃塞俄比亚人适应高海拔模式的综合模型奠定基础，了解它们是如何产生的，以及了解每种模式是否存在特定的风险或益处是很重要的。这项研究的更广泛影响包括在研究的所有阶段扩大与埃塞俄比亚科学家、研究志愿者和医务人员的伙伴关系。更广泛的影响还包括增加对健康人群对缺氧的不同成功反应的理解。这有助于理解为什么有些人在生病期间（以缺氧为特征的疾病占美国所有死亡人数的三分之二）或在前往高原游玩、商务、科学或军事活动期间对缺氧反应成功。

Modern humans live at high elevations in a number of areas of the world, notably the Himalayas, the Andes and the mountains of Ethiopia. Research has indicated that the biological mechanisms by which they cope with the stresses encountered at these elevations are quite different, a vivid demonstration of the plastic nature of human adaptability. The goal of the study is to discover the mechanisms underlying the distinctive Ethiopian pattern of adaptation to high altitude. The scientific merit of this research is figuring out how Ethiopian highlanders have apparently normal levels of oxygen saturation of hemoglobin and hemoglobin concentration even when they live at high altitudes where every breath of air contains fewer oxygen molecules as compared with sea level. They contrast with high-altitude natives in other parts of the world and with visitors to high altitude, all of whom have low oxygen saturation compared with sea level. The research is designed to 1) test two alternative hypotheses to explain why native residents of the NW highlands of Ethiopia achieve levels of oxygen saturation of hemoglobin in the normal sea-level range despite hypoxic stress, and 2) determine whether residents of the distant SE Highlands of Ethiopia share this pattern of high-altitude adaptation. The first objective will be achieved by comparing two samples of 85 healthy adults of the Amharic ethno-linguistic group residing in the Semien Mountains Region of NW Ethiopia, one resident at high altitude (3700-4000m) and the other at low altitude (1500m). With these samples, the study will investigate two alternative hypotheses to explain why native residents of the NW highlands of Ethiopia achieve levels of oxygen saturation of hemoglobin in the normal sea-level range despite hypoxic stress. One hypothesis reasons that the Ethiopian highlanders have more efficient transfer of oxygen from ambient air to arterial blood; it will be supported if both oxygen saturation of hemoglobin and the partial pressure of oxygen in arterial blood are in the normal sea-level range, rather than lower. The alternative, hypothesis reasons that the Ethiopian highlanders have an increase in the affinity of hemoglobin for oxygen; it will be supported if oxygen saturation of hemoglobin is in the normal sea level range, even though the partial pressure of oxygen in arterial blood is relatively low as expected for high altitude. The second objective of the proposed research will be achieved by comparing two similar samples of the Oromo ethno-linguistic group residing in the Bale Plateau Region of SE Ethiopia at high and low altitudes that are similar to those of the Amharic ethno-linguistic group of NW Ethiopia. Measures of oxygen saturation of hemoglobin and hemoglobin concentration will confirm or deny a pattern of adaptation similar to that of the NW highlanders. Filling the gap in knowledge of Ethiopian adaptations is important for understanding the full range of possibilities of adaptation to high-altitude hypoxia and laying the foundation for developing a comprehensive model of the Andean, Tibetan, and Ethiopian patterns of adaptations to high-altitude, understanding how they come about, and knowing whether there are particular risks or benefits associated with each pattern.The broader impact of the research includes expanded partnerships with Ethiopian scientists, research volunteers and medical personnel through all phases of research. The broader impact also includes adding to understanding of the different successful responses to hypoxia among healthy people. This can help to understand why some people respond successfully to hypoxia during illness (diseases characterized by hypoxia account for two-thirds of all deaths in the US) or during travel to altitude for pleasure, business, scientific, or military activities.