About the Lab
Humans have lived at high altitude for thousands of years despite the unavoidable stress imposed by hypoxia. While evidence for adaptation in native highlanders has been provided, the precise physiological and molecular processes and the specific genetic variants that may underlie unique characteristics in these populations are unknown. Our work takes an integrative physiological genomics approach to address these questions in native highland populations from the Tibetan Plateau and their counterparts in the Andes.
Genetic adaptation in highland populations
Signals of genetic adaptation to high altitude that our group and others recently identified are among the strongest in the human genome. Several of these genetic factors are related to oxygen sensing and response and are likely linked to important physiological traits. Three of these selection candidate genes (EPAS1, EGLN1, PPARA) are associated with relatively lower hemoglobin concentration in high-altitude Tibetan residents.
Highland groups exhibit differences in a suite of traits including, but not limited to, hemoglobin concentration, oxygen saturation, birth weight, and ventilation. These differences suggest that these populations have adapted to high altitude in different ways.
Our current work aims to determine: 1) the physiological relevance of hemoglobin concentration ([Hb]) in Tibetans which is, unlike lowland groups and high-altitude natives in the Andes, within the range expected at sea-level, and 2) whether physiological changes (specifically related to exercise capacity and oxygen transport) are related to epigenetic and adaptive genetic factors, including those previously associated with lower [Hb].
Division of Physiology
Department of Medicine, School of Medicine
University of California, San Diego
9500 Gilman Drive, 0623A
La Jolla CA 92093-0623 USA