- Dec 2017
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These results suggest that high-altitude adaptation in Tibetans has resulted from local positive selection on several distinct genes.
The presence of the hapolotypes discovered by the XP-EHH and iHS assays are the result of positive selection.
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The strong and significant association between Hb concentration and haplotype variation at EGLN1 and PPARAprovides evidence of a genetic contribution to a form of high-altitude adaptation that appears to be unique to Tibetan populations.
The variations in the PPARA and EGLN1 genes seen in the Tibetan highlanders correlate to decreased hemoglobin levels. The decreased hemoglobin levels in the Tibetan inhabitants that is negatively correlated to hemoglobin concentration provides genetic evidence for high altitude adaptation.
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Although PPARA has not previously been considered as a candidate gene for high-altitude adaptation, it interacts with components of the HIF pathway
Hypoxia-inducible factor 1-mediated inhibition of peroxisome proliferator-activated receptor alpha expression during hypoxia (2002).
It was found that PPARA is (under hypoxic condition) inhibited by HIF1-alpha. In Tibetan highlanders the PPARA gene is adapted so that it can function in the presence of HIF, though this mechanism is unknown.
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Each additional copy of an advantageous haplotype at either locus decreases Hb concentration by ~1.7 g/dl on average
Having the adapted versions of the genes EGLN1 and PPARA decreased the amount of hemoglobin in a Tibetan highlander in increasing amount as multiple copies of the haplotype are seen. For example; one copy of the Tibetan EGLN1 gene slightly decreases the hemoglobin concentration, but two copies of the Tibetan EGLN1 gene significantly reduces hemoglobin concentration.
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On average, the XP-EHH and iHS intersections contained 2.7 and 1.4 genes, respectively, significantly fewer than the six (P < 0.05) and five (P < 0.01) genes actually observed.
The researchers resampled and calculated the genes undergoing positive selection. These genes were originally found using the XP-EHH and iHS test. It was discovered that a decrease in gene numbers found by both tests (from 6 to 2.7 and from 5 to 1.4).
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EGLN1 was identified by both,
After running the XP-EHH and iHS testing EGLN1 was determined to be a gene that was undergoing local positive selection. Meaning that the gene was currently providing an adaptive advantage to the person who had it, and was increasing in occurrence in that population.
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lower incidence of reduced birth weight, and reduced
Beall, C. M. (2007). Two routes to functional adaptation: Tibetan and Andean high-altitude natives. Proceedings of the National Academy of Sciences, 104(Supplement 1), 8655-8660. doi:10.1073/pnas.0701985104
These are some of the physiological traits that were found to be different between populations of Tibetan highlanders and Han Chineese. These include but are not limited to: less oxygen in the arteries, higher breathing rate at rest, loss of low oxygen induced blood vessel constriction, and lower occurrences of decreased birth weight, as well as decreased hemoglobin concentrations.
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Tibetans exhibit a distinct suite of
https://news.nationalgeographic.com/news/2004/02/0224_040225_evolution.html Adaptations result in changed phenotype. As the Tibetan highlanders adapted to their high altitude environment, they underwent changes to their physiology as to better acclimate to their environment.
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It is plausible that the diminished Hb levels found in Tibetans offset complications associated with sustained high Hb levels (for instance, hyperviscosity) seen in non-Tibetans exposed to high-altitude conditions (10, 11). Alternatively, decreased Hb levels could be a side effect of other phenotypes that are the actual targets of natural selection.
Overall, the decreased hemoglobin levels seen in the Tibetan highlanders may be the result of variants in PPARA and EGLN1 haplotypes. However, the decreased hemoglobin levels could a side effect of a currently unknown phenotype, which may be the actual target of natural selection.
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Because sex and age affect Hb concentration in Tibetans and Han Chinese, and the age effect differs between males and females
This paper discusses the effect of gender on hemoglobin levels in Han Chinese and Tibetan Plateau inhabitants as a mechanism for high altitude adaptation. In Han populations a correlation was seen between increased altitude and increased hemoglobin levels (men having higher hemoglobin concentration than women), this correlation was not see in Tibetan highland inhabitants, or between genders of Tibetan highland individuals.
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