Oromo have moved to HA only in the early 1500 s [22], [23], the Amhara have inhabited altitudes above 2500 m for at least 5 ky and altitudes around 2300–2400 m for more than 70 ky [24], [25]. Therefore, sufficient time has elapsed for the Amhara to have evolved genetic adaptations to hypoxia.

higher O2 sat also associated with higher reproductive success [15]; though the locus underlying this effect has not yet been identified

Andeans show some reduction in O2 sat, but a marked increase in Hb levels [11], Tibetans present markedly low O2 sat, but relatively little increase in Hb levels [12], and Amhara in Ethiopia present little reduction in O2 sat or increase in Hb levels [13], [14]

For the Omoro -- who are relative newcomers to high altitude -- the researchers also found differences between highlanders and lowlanders in DNA methylation, a chemical process that causes changes in gene activity, but doesn't necessarily alter the genetic code. While the differences aren't linked to hemoglobin levels, the results suggest that such changes may play a role in the early stages of high altitude adaptation

two genes, egl nine homolog 1 (EGLN1) (which inhibits haemoglobin production under high oxygen concentration) and peroxisome proliferator-activated receptor alpha (PPARA), were also identified to be positively selected

50 Tibetans and 40 Han Chinese from Beijing

So what adaptation have the Ethiopian highlanders' bodies evolved to survive at high altitude? "Right now we have no clue how they do it,"

The Andeans adapted to the thin air by developing an ability to carry more oxygen in each red blood cell.

oxygen-regulated machinery has an important role in cancer. In tumors, the oxygen-regulated machinery is utilized to stimulate blood vessel formation and reshape metabolism for effective proliferation of cancer cells. Intense ongoing efforts in academic laboratories and pharmaceutical companies are now focused on developing drugs that can interfere with different disease states by either activating, or blocking, the oxygen-sensing machinery.

adaptive processes controlled by oxygen sensing include the generation of new blood vessels and the production of red blood cells.

Our immune system and many other physiological functions are also fine-tuned by the O2-sensing machinery.

Kaelin also showed that cancer cells lacking a functional VHL gene express abnormally high levels of hypoxia-regulated genes; but that when the VHL gene was reintroduced into cancer cells, normal levels were restored.