This special genetic haplotype, called EPAS1, occurs at greater frequencies in populations dwelling at higher altitudes, meaning that the higher an individual lives in the Himalayas, the more likely he or she is to carry the haplotype.
“I was not expecting to find such a significantly high correlation between the EPAS1 haplotype and altitude,” says Qasim Ayub, corresponding author of the study, published February online in Human Genetics. “This is among the highest genetic correlations reported for any environmental trait,” he adds.
Ayub, scientist at the Wellcome Trust Sanger Institute in Hinxton, UK, worked with partners at Sanger, the University of Leicester, Leiden University Medical Centre, the Netherlands, BGI-Shenzhen, and the University of Bern in Switzerland, to understand high-altitude adaptation with a view to developing a cure for people suffering from hypoxia, or oxygen deficiency.
“Adaptive human traits are interesting to study from the evolutionary point of view and there is interest in finding out how humans lived and reproduced successfully in such harsh climatic conditions with low-oxygen concentrations in the Himalayas,” he says. “The hope is that by understanding physiological adaptations to hypoxia we can in some way benefit patients suffering from ischaemia and chronic hypoxia.” EPAS1, found within the endothelial PAS domain protein 1, is believed to have been inherited from extinct Denisovans, and has been reported in DNA samples obtained from Tibetans and Sherpas. Ayub and colleagues genotyped 19 genetic variants in the EPAS1 region in approximately 1,500 samples from 55 different populations residing in the Himalayas, especially in Bhutan, Nepal, and Tibet, as well as in China, India, Mongolia, Pakistan and in the Caucuses.
The researchers found that the core Denisovan haplotype was present at a high frequency not only in Tibetans and Sherpas but also among many populations in the Himalayas, and that the haplotype showed a significant correlation with altitude.
“Our conclusion is that the haplotype arose in a common ancestor that was widespread in South and East Asia and its high frequency in the Himalayan populations was due to the fact that the haplotype provided some adaptive benefit to people living at high altitudes,” says Ayub.
Emilia Huerta-Sanchez, assistant professor at the University of California, Merced, describes the findings as “exciting”. “We didn’t know whether Tibetans were the only population with the Denisovan-like haplotype at high frequency,” says Huerta-Sanchez, noting that many populations in the Himalayas have the Denisovan-like haplotype at high frequency.
“Interestingly, they also find a correlation between the haplotype frequency and altitude, which supports the hypothesis that this haplotype confers a beneficial advantage at high altitude,” she says.
This piece was produced by SciDev.Net’s South Asia desk.