Mean hemoglobin (Hb) concentration of about 3 500 subjects derived from 17 
studies of Himalayan highlanders (Tibetans, Sherpas, and Ladakhis) was compared 
with lowlanders (Chinese Han, Indian Tamils) lived in the Himalayas, and 
European climbers during Everest expeditions as well as Andean natives. The 
results found that Hb concentration in Himalayan highlanders was systemically 
lower than those reported for Andean natives and lowland immigrants. These 
comparative data demonstrated that a healthy native population may successfully 
reside at high altitude without a significant elevation in Hb, and the lower Hb 
levels of Himalayan highlanders than those of migrated lowlanders and Andean 
natives are an example of favourable adaptation over the generations. In 
addition, excessive polycythemia has frequently been used as a marker of chronic 
mountain sickness (CMS). Altitude populations who have a higher Hb concentration 
also have a higher incidence of CMS. The low Hb in Himalayans suggested as 
showing adaptation over many generations in Tibetan stock. Recent work in Tibet, 
suggested that Tibetans there may have adapted to high altitude as a result of 
evolutionary pressure selecting for genes which give an advantage at altitude. 
All of the population genomic and statistical analysis indicated that EPAS1 and 
EGLN1 are mostly likely responsible for high altitude adaptation and closely 
related to low Hb concentration in Tibetans. These data supported the hypothesis 
that Himalayan highlanders have evolved a genetically different erythropoietic 
response to chronic hypoxia by virtue of their much longer exposure to high 
altitude.