Modern humans have occupied almost all possible environments globally since 
exiting Africa about 100,000 years ago. Both behavioral and biological 
adaptations have contributed to their success in surviving the rigors of 
climatic extremes, including cold, strong ultraviolet radiation, and high 
altitude. Among these environmental stresses, high-altitude hypoxia is the only 
condition in which traditional technology is incapable of mediating its effects. 
Inhabiting at >3,000-m high plateau, the Tibetan population provides a widely 
studied example of high-altitude adaptation. Yet, the genetic mechanisms 
underpinning long-term survival in this environmental extreme remain unknown. We 
performed an analysis of genome-wide sequence variations in Tibetans. In 
combination with the reported data, we identified strong signals of selective 
sweep in two hypoxia-related genes, EPAS1 and EGLN1. For these two genes, 
Tibetans show unusually high divergence from the non-Tibetan lowlanders (Han 
Chinese and Japanese) and possess high frequencies of many linked sequence 
variations as reflected by the Tibetan-specific haplotypes. Further analysis in 
seven Tibetan populations (1,334 individuals) indicates the prevalence of 
selective sweep across the Himalayan region. The observed indicators of natural 
selection on EPAS1 and EGLN1 suggest that during the long-term occupation of 
high-altitude areas, the functional sequence variations for acquiring biological 
adaptation to high-altitude hypoxia have been enriched in Tibetan populations.