Tibetans underwent ”fastest genetic change” in human history to thrive at high altitude

Tibetans split off from the Han Chinese some 3,000 years ago and since then rapidly developed a unique ability to thrive at high altitudes and low oxygen levels, researchers have ascertained after comparing the genomes of 50 Tibetans and 40 Han Chinese.

The genome-wide comparison, carried out by evolutionary biologists at the University of California, Berkeley, uncovered more than 30 genes with DNA mutations that have become more prevalent in Tibetans than Han Chinese, nearly half of which are related to how the body uses oxygen. One mutation in particular spread from fewer than 10 percent of the Han Chinese to nearly 90 percent of all Tibetans.

Rasmus Nielsen, UC Berkeley professor of integrative biology, who led the statistical analysis, said: “This is the fastest genetic change ever observed in humans. For such a very strong change, a lot of people would have had to die simply due to the fact that they had the wrong version of a gene.”

The widespread mutation in Tibetans is near a gene called EPAS1, a so-called “super athlete gene” identified several years ago and named because some variants of the gene are associated with improved athletic performance, Nielsen said. The gene codes for a protein involved in sensing oxygen levels and perhaps balancing aerobic and anaerobic metabolism.

Nielsen, a computational evolutionary biologist, mines genomic information to discover genetic changes driven by natural selection as humans and animals have adapted to new environments. Changes in the frequency of DNA mutations are one clue.

He said: “You look for rapid evolution in genes because there must be something important about that gene forcing it to change so fast. The new finding is really the first time evolutionary information alone has helped us pinpoint an important function of a gene in humans.”

Adaptation to low oxygen levels has allowed many peoples, from Andeans to Tibetans, to live at high altitude.

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When people from lower elevations move above about 13,000 feet, where oxygen levels are about 40 percent lower than at sea level, they typically tire easily, develop headaches, produce babies with lower birth weights and have a higher infant mortality rate.

Tibetans have none of these problems, despite lower oxygen saturation in the blood and lower haemoglobin levels. Haemoglobin, which gives blood its red colour, binds and transports oxygen to the body”s tissues.

Nielsen used genome data produced by the Beijing Genomics Institute (BGI) in Shenzhen, China’s flagship genome centre, to tease out the genetic changes associated with these physiological changes.

The analysis revealed that the common ancestors of Tibetans and Han Chinese split into two populations about 2,750 years ago, with the larger group moving to the Tibetan plateau. That group eventually shrank, while the low-elevation Han population expanded dramatically. Today, the Han Chinese are the dominant ethnic group in mainland China. The Tibetan branch either merged with the people”s already occupying the Tibetan plateau, or replaced them.

Nielsen said: “We can’t distinguish intermixing and replacement. The Han Chinese and Tibetans are as different from one another as if the Han completely replaced the Tibetans about 3,000 years ago.”

The Tibetan and Han Chinese genomes are essentially identical in terms of the frequency of polymorphisms in the roughly 20,000 genes, though some 30 genes stood out because of dramatic differences between the Tibetans and the Han.

Nielsen said: “We made a list of the genes that changed the most and what was fascinating was that, bing!, at the top of that list was a gene that had changed very strongly, and it was related to the response to oxygen.”

The findings of the research appear in the journal Science.

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