A new study published online in the journal Nature Communications sheds light on high-altitude adaptations in modern Tibetans. Also, it suggests that Tibetans are a mixture of ancestral populations related to the modern Nepalese Sherpa and Han Chinese.
Tibetans. Image credit: Antoine Taveneaux / CC BY-SA 3.0.
“The Tibetan genome appears to arise from a mixture of two ancestral gene pools. One migrated early to high altitude and adapted to this environment. The other, which migrated more recently from low altitudes, acquired the advantageous alleles from the resident high-altitude population by interbreeding and forming what we refer to today as Tibetans,” explained Prof Anna Di Rienzo from the University of Chicago.
High elevations are challenging for humans because of low oxygen levels but Tibetans are well adapted to life above 13,000 feet. Due to physiological traits such as relatively low hemoglobin concentrations at altitude, Tibetans have lower risk of complications, such as thrombosis, compared to short-term visitors from low altitude.
Unique to Tibetans are variants of the EGLN1 and EPAS1 genes, key genes in the oxygen homeostasis system at all altitudes. These variants were hypothesized to have evolved around 3,000 years ago, a date which conflicts with much older archaeological evidence of human settlement in Tibet.
To shed light on the origins of these gene variants, the scientists obtained genome-wide data from 69 Nepalese Sherpa, an ethnic group related to Tibetans.
These were analyzed together with the genomes of 96 unrelated individuals from high-altitude regions of the Tibetan plateau, worldwide genomes from HapMap3 and the Human Genome Diversity Panel, as well as data from Indian, Central Asian and two Siberian populations, through multiple statistical methods and sophisticated software.
They found that, on a genomic level, modern Tibetans carry a roughly even mixture of two ancestral genomes: one a high-altitude component shared with Sherpa and the other a low-altitude component shared with lowlander East Asians.
The low-altitude component is found at low to nonexistent frequencies in modern Sherpa, and the high-altitude component is uncommon in lowlanders. This strongly suggested that the ancestor populations of Tibetans interbred and exchanged genes, a process known as genetic admixture.
Tracing the history of these ancestor groups through genome analysis, the team identified a population size split between Sherpa and lowland East Asians around 20,000 to 40,000 years ago, a range consistent with proposed archaeological, mitochondria DNA and Y chromosome evidence for an initial colonization of the Tibetan plateau around 30,000 years ago.
In addition to the EPAS1 and EGLN1 genes, the team discovered two other genes with a strong proportion of high-altitude genetic ancestry, HYOU1 and HMBS. The former is known to be up-regulated in response to low oxygen levels and the latter plays an important role in the production of heme, a major component of hemoglobin.
“There is a strong possibility that these genes are adaptations to high altitude. They represent an example of how the ancestry-based approach used in this study will help make new discoveries about genetic adaptations,” Prof Di Rienzo concluded.
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Choongwon Jeong et al. 2014. Admixture facilitates genetic adaptations to high altitude in Tibet. Nature Communications 5, article number: 3281; doi: 10.1038/ncomms4281
