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Genetic adaptation to high altitudes in Tibet
#1
A new genomic study on people living in the Tibetan plateau has identified a novel mechanism of population adaptation to local environments, in this case specifically to high altitudes. The study, in Nature Communications, found that genetic adaptations beneficial for survival at high altitudes arose approximately 30,000 years ago in ancestors of contemporary Sherpas. Admixture then allowed these genes to be passed on to more recent migrants originating at lower elevations. These advantageous genetic adaptations were amplified by natural selection in the gene pool of modern Tibetans.

The study was carried out by researchers in the University of Chicago, Oxford University Clinical Research Unit in Kathmandu, Nepal, the Mountain Medicine Society of Nepal, Howard Hughes Medical Institute, Maryland and Case Western Reserve University in Ohio. It examined genome-wide data from 69 Nepalese Sherpa, an ethnic group related to Tibetans compared to 96 unrelated individuals from high-altitude regions of the Tibetan plateau. Comparisons were also performed to genomes derived from HapMap3 and the Human Genome Diversity Panel and from Indian, Central Asian and two Siberian populations.

Modern Tibetans have physiological traits that make them well equipped to cope with high altitudes. This includes relatively low haemoglobin levels. Two of the genes which were already to be known to be variant in this population were EGLN1 and EPAS1, which are key to oxygen homeostasis. Previous studies had hypothesised that variants in these genes arose approximately 3000 years ago, but this was at odds with archaeological evidence as well as studies on mitochondrial DNA and Y chromosome evidence. In the current study, the researchers were able to confirm that high-altitude adaptations in the EGLN1 and EPAS1 genes, associated with lower haemoglobin concentration, arose approximately 30,000 years ago and that these adaptations are enriched in the modern Tibetan genome. This suggests that the more recent migrants from lower altitudes acquired the advantageous high altitude variations upon interbreeding with highlanders via admixture. This is a novel mechanism of adaptation of a population to local environment which is independent of selection of new mutations. On a genomic level, modern Tibetans have traits in common with modern Sherpas and with Han Chinese. Apart from the already recognised EGLN1 and EPAS1 genes, the researchers identified other genes not previously known to be associated with high altitude adaptation, including HYOU1, which is enhanced in response to low oxygen and HMBS, which is involved in the production of haem. Dr Anna Di Rienzo, the lead author on the study, concluded that "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."

Sources

http://www.eurekalert.org/pub_releases/2...020714.php

JEONG, C., ALKORTA-ARANBURU, G., BASNYAT, B., NEUPANE, M., WITONSKY, D.B., PRITCHARD, J.K., BEALL, C.M. AND DI RIENZO, A., 2014. Admixture facilitates genetic adaptations to high altitude in Tibet. Nature Communications 5, Article number: 3281; doi:10.1038/ncomms4281
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#2
The chromosomal locations that are so important for Tibetans to live at high elevations are locations that have an excess of genetic ancestry from their high-altitude ancestral gene pool, This is a new tool we can use to identify advantageous alleles in Tibetans and other populations in the world that experienced this type of admixture and selection.
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