Some highland populations have genetic adaptations that enable their successful 
existence in a hypoxic environment. Tibetans are protected against many of the 
harmful responses exhibited by non-adapted populations upon exposure to severe 
hypoxia, including elevated hemoglobin concentration (i.e., polycythemia). 
Recent studies have highlighted several genes subject to natural selection in 
native high-altitude Tibetans. Three of these genes, EPAS1, EGLN1 and PPARA, 
regulate or are regulated by hypoxia inducible factor, a principal controller of 
erythropoiesis and other organismal functions. Uncovering the molecular basis of 
hypoxic adaptation should have implications for understanding hematological and 
other adaptations involved in hypoxia tolerance. Because the hypoxia response 
involves a variety of cardiovascular, pulmonary and metabolic functions, this 
knowledge would improve our understanding of disease mechanisms and could 
ultimately be translated into targeted therapies for oxygen deprivation, 
cardiopulmonary and cerebral pathologies, and metabolic disorders such as 
diabetes and obesity.