Ethiopian Adaptation to High-altitude Hypoxia

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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.