Genetic Adaptations to High Altitude

The atmosphere surrounding the mountain villages in the high peaks of Tibet, which stretch about 14,000 feet above sea level, contains 40 percent less oxygen than the air at sea level. That harsh environment has felled many avid mountain climbers, but the long-time inhabitants of the high peak mountain villages seem to thrive in the thin air. New genetic analysis of this population is starting to explain why.

Scientists from the University of California, Berkeley sequenced the exomes–the three percent of the genome that codes for proteins–of 50 Tibetans and 40 Han Chinese, uncovering more than 30 genes with DNA mutations that have become more prevalent in Tibetans than Han Chinese. Nearly half of these genes help regulate how the body uses oxygen, according to the study, published today in the journal Science. Scientists say the results illustrate the most recent example of natural selection in humans.

One particularly widespread mutation in Tibetans–it is present in fewer than 10 percent of the Han Chinese and nearly 90 percent of all Tibetans–lies near a gene called EPAS1. (A second study in the same issue also picked up this variant.) Earlier research suggests this gene plays a role in regulating hemoglobin in response to oxygen. According to Rasmus Nielsen, a professor of integrative biology at Berkeley who led the statistical analysis for one of the studies, this gene was dubbed “super athlete gene” when it was first identified several years ago because some variants are associated with improved athletic performance.

People with two copies of the gene living at high altitude have fewer red blood cells and lower hemoglobin levels than those with one or no copies. The finding may explain in part Tibetans’ resistance to mountain sickness; when people living at sea level travel to high altitudes, their bodies compensate for the low oxygen by making more red blood cells. That makes the blood more viscous, making it difficult to oxygenate tissue and increasing risk of thrombosis and miscarriage. It’s not yet clear how people with two copies of the variant cope with lower hemoglobin levels, though they appear to have similar oxygen levels to those without the mutation.