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phenotypic data were reported. On the one hand, it seems unlikely that a transcription factor regulating the induction of dozens of genes accounts for the Tibetan–Andean differences, because a change of this sort would have many downstream effects. Perhaps more likely is genetic variation in one or more of the ≥70 genes induced by HIF1 or in the biochemical pathways in which they participate. On the other hand, considering that the Tibetan–Andean differences involve many traits and apparently have accumulated in a relatively short time of ≤25,000 years, perhaps a change in a regulatory mechanism is the underlying mechanism.

In summary, measures of oxygen transport reveal that Andean and Tibetan populations have large quantitative differences in numerous physiological and molecular traits involved in oxygen delivery. The hypothesis is that evolutionary processes have tinkered differently in the two founding populations and their descendents, with the result that the two populations followed different routes to the same functional outcome of successful oxygen delivery. That conclusion will remain tentative, however, until the responsible genes are identified.


We thank the thousands of high-altitude natives on two continents who participated in this research and welcomed us into their communities. The research reported here was supported in part by grants from the National Science Foundation (Grant 215747), the National Institutes of Health (Grants M01 RR-00080, HL-60917, and M01 RR-018390), the Luce Foundation, and the National Geographic Committee on Research and Exploration. Amy Rezac and Jaleesa Avak prepared the figures. This research was conducted in collaboration with numerous scientists in the United States, including G. M. Brittenham, S. C. Erzurum, B. D. Hoit, K. P. Strohl, and members of their laboratories, and in collaboration with the Tibet Academy of Social Sciences, Lhasa, Tibet Autonomous Region, and the Instituto Boliviano de Biología de Altura, La Paz, Bolivia.

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