High elevation adaptations in current day Tibetans likely originated 30,000 years ago. These genes were passed on to modern day Tibetans, who migrated from lower elevations, via population mixing, and then amplified by natural selection, according to a new study by scientists from the University of Chicago and Case Western Reserve University, published in Nature Communications.

This transfer of beneficial mutations followed by selective enrichment represents a novel mechanism for adapting to new environments. On a genomic level, modern Tibetans evidently descend from populations related to modern Sherpa and Han Chinese.

"The Tibetan genome appears to arise from a mixture of two ancestral gene pools," said Anna Di Rienzo, professor of human genetics at the University of Chicago and corresponding author of the study. "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."

Low oxygen levels at high elevations make life difficult, but Tibetans are well suited for life above 13,000 feet. Relatively low hemoglobin concentrations shield Tibetans from complications such as thrombosis, which affect low altitude visitors. Variants of the EGLN1 and EPAS1 genes, which are central to oxygen homeostasis at all altitudes, were found to be uniquely Tibetan.

"To shed light on the evolutionary origins of these gene variants, Di Rienzo and her team, led by first author Choongwon Jeong, graduate student at the University of Chicago, 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," according to a release announcing the findings.

The statement continues, "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."

The team identified a split occurring between Sherpa and lowland East Asians around 20,000 to 40,000 years ago, by tracing their history through genome analysis. These results are consistent with archeological, mitochondria DNA and Y chromosome evidence.

"This is a good example of evolution as a tinkerer," said Cynthia Beall, professor of anthropology at Case Western Reserve University and co-author on the study. "We see other examples of admixtures. Outside of Africa, most of us have Neanderthal genes-about 2 to 5 percent of our genome-and people today have some immune system genes from another ancient group called the Denisovans."