Study of people living at high altitude focuses on key gene

A new genetic study of Ethiopians living at high altitude reveals how humans evolved to cope with living in thin air.
(Allen Thomas / Associated Press)
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People living at some of the world’s highest elevations seem to have evolved to cope with the thinner air, according to a new study.

A team led by Rasmus Nielsen and Emilia Huerta-Sanchez of UC Berkeley have pinpointed a gene, BHLHE41, that appears responsible for high-altitude Ethiopians’ ability to adapt to low-oxygen environments.

Anyone who has climbed Half Dome or played baseball in Colorado knows that high elevation causes shortness of breath and other symptoms of “hypobaric hypoxia,” due to low pressure and oxygen. The problems can be even more serious.


“Fertility levels drop and birth weights are low in individuals who are not genetically adapted to high elevations,” said Huerta-Sanchez, a postdoctoral scholar and the lead author of the study, published in the August issue of Molecular Biology and Evolution.

But some people have settled places extremely high in the sky, such as the Tibetan and Andean plateaus and the Ethiopian highlands. How do they not suffer the same effects?

Previous studies on Tibetans and Andeans revealed that their DNA contained genetic variations that people at lower elevation possessed at lower frequencies. The findings strongly implied a genetic adaptation to living up high.

To look for a similar genetic adaptation in Ethiopians at high elevation, Huerta-Sanchez and her collaborators compared previously collected genetic data of the Amhara, Tigray, and Oromo ethnic groups living at about 6,000 feet to the genes of the low-altitude Afar and Anuak people at 1,500 feet.

Huerta-Sanchez wrote that one of the biggest challenges of the study was accounting for past intermixing between the high-altitude Ethiopians and those at lower altitude and with people from other parts of Africa and Europe. Past research showed that 40% to 50% of the Ethopians’ genome could be traced to mixing with Europeans 3,000 years ago. The shared ancestry could lead the researchers to falsely conclude that a variant of a high-altitude gene had evolved within the Ethiopian population when in fact it was simply inherited from elsewhere.

Using statistical simulations, Huerta-Sanchez and her team were able to account for the past mixing. They performed a technique called a genome scan, in which the entire genetic code is scanned for genes that may provide some adaptive benefit, and found a version of one gene, BHLHE41, at high frequency in all three high-altitude populations, but not down low. According to the study, BHLHE41 interacts with a key protein to regulate the body’s response to low oxygen, and is also involved with circadian rhythms, perhaps affecting sleep cycles. Although they still have to work out the gene’s specific function, statistical analysis shows that its high frequency in the population probably is the result of natural selection, the researchers said.


The team was surprised, however, that the same gene was not identified in other studies of Ethiopians, or in studies of Andeans and Tibetans. Huerta-Sanchez suggested that the discrepancy with other Ethiopian studies could be due to a number of factors, including differences in the low-altitude control groups, the precise location of the Ethiopian populations and the way that intermixing with other parts of the world was dealt with (or not).

Although the genetic basis for adaptation to high elevation was different in all of these studies, Huerta-Sanchez was encouraged to see some common ground — all of the genes identified are involved with the pathway that deals with low oxygen supply. The destination is the same, but the genetic journey is different.

“It’s a nice example of convergent evolution,” Huerta-Sanchez said.

You can read a summary of the study here.

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