An international team of researchers has discovered a gene in Tibetan people that allows them to live and work at altitudes of more than two miles above sea level without getting ill, suggesting natural selection over 10,000 years has caused them to evolve differently from their lowland ancestors.

You can read about the study by Dr Hugh Montgomery, a Clinical Physiology professor at University College London, in the UK, and other researchers from England, Ireland, China and the US, in the 7 June online ahead of print issue of the Proceedings of the National Academy of Sciences, PNAS.

A previous study reported in Science a month ago suggested that Tibetans are genetically adapted to live at high altitude. In this latest PNAS study the team identified a gene variant linked to low hemoglobin in the blood that might explain why Tibetans thrive in a low-oxygen environment.

High altitude is a problem for humans and other animals because of the lack of oxygen, and our bodies respond to this by making more hemoglobin, a compound in the blood that carries oxygen. However, too much hemoglobin makes the blood too viscous and thick, causing chronic mountain sickness.

But Tibetans don’t have this problem because despite the fact they live at high altitude, their hemoglobin levels stay relatively low, making them less likely to have the disease. The researchers postulated that the lack of oxygen has acted as an agent of natural selection in the Tibetans’ gene pool and decided to look for evidence in their genomes.

For the study the researchers collected blood samples from nearly 200 Tibetan villagers in three different regions high in the Himalayas (3,500 m altitude and higher) and compared their DNA with that of their lowland counterparts in China.

They found that the Tibetans carried a special variant of a gene carried by all humans that is called called EPAS1 and is located on chromosome 2: EPAS1 helps produce red blood cells and maitain hemoglobin concentration in the blood.

While the presence of the gene may explain how Tibetans keep their hemoglobin levels relatively low despite living at high altitude, the researchers are still puzzled as to how this ensures their tissues get enough oxygen: they suggest this is just the beginning and not the end of the story.

Montgomery said studies like this should help us better understand why some people cope better than others when they have diseases that cause low blood oxygen, such as lung disease and certain heart conditions. Another benefit could be to help predict risk for altitude sickness among those of us who live nearer to sea level than the people of Tibet.

“Natural selection on EPAS1 (HIF2α) associated with low hemoglobin concentration in Tibetan highlanders.”
Cynthia M. Beall, Gianpiero L. Cavalleri, Libin Deng, Robert C. Elston, Yang Gao, Jo Knight, Chaohua Li, Jiang Chuan Li, Yu Liang, Mark McCormack, Hugh E. Montgomery, Hao Pan, Peter A. Robbins, Kevin V. Shianna, Siu Cheung Tam, Ngodrop Tsering, Krishna R. Veeramah, Wei Wang, Puchung Wangdui, Michael E. Weale, Yaomin Xu, Zhe Xu, Ling Yang, M. Justin Zaman, Changqing Zeng, Li Zhang, Xianglong Zhang, Pingcuo Zhaxi, and Yong Tang Zheng.
PNAS, published ahead of print June 7, 2010
DOI:10.1073/pnas.1002443107

Source: UCL.

Written by: Catharine Paddock, PhD