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human is one of Organisms at high altitude



Over 140 million people live permanently at high altitudes (>2,500 m) in North, Central and South America, East Africa, and Asia, and have flourished for millennia in the exceptionally high mountains, without any apparent complications. For normal human populations, a brief stay at these places can risk mountain sickness. For the native highlanders, there are no adverse effects to staying at high altitude.

 The physiological and genetic adaptations in native highlanders involve modification in the oxygen transport system of the blood, especially molecular changes in the structure and functions of hemoglobin, a protein for carrying oxygen in the body.[48][50] This is to compensate for the low oxygen environment. This adaptation is associated with developmental patterns such as high birth weight, increased lung volumes, increased breathing, and higher resting metabolism.


The genome of Tibetans provided the first clue to the molecular evolution of high-altitude adaptation in 2010. Genes such as EPAS1, PPARA and EGLN1 are found to have significant molecular changes among the Tibetans, and the genes are involved in hemoglobin production. These genes function in concert with transcription factors, hypoxia inducible factors (HIF), which in turn are central mediators of red blood cell production in response to oxygen metabolism.[54] Further, the Tibetans are enriched for genes in the disease class of human reproduction (such as genes from the DAZ, BPY2, CDY, and HLA-DQ and HLA-DR gene clusters) and biological process categories of response to DNA damage stimulus and DNA repair (such as RAD51, RAD52, and MRE11A), which are related to the adaptive traits of high infant birth weight and darker skin tone and, are most likely due to recent local adaptation.

 Among the Andeans, there are no significant associations between EPAS1 or EGLN1 and hemoglobin concentration, indicating variation in the pattern of molecular adaptation.[56] However, EGLN1 appears to be the principal signature of evolution, as it shows evidence of positive selection in both Tibetans and Andeans. The adaptive mechanism is different among the Ethiopian highlanders. Genomic analysis of two ethnic groups, Amhara and Oromo, revealed that gene variations associated with hemoglobin differences among Tibetans or other variants at the same gene location do not influence the adaptation in Ethiopians.[58] Instead, several other genes appear to be involved in Ethiopians, including CBARA1, VAV3, ARNT2 and THRB, which are known to play a role in HIF genetic functions.

 The EPAS1 mutation in the Tibetan population has been linked to Denisovan-related populations. The Tibetan haplotype is more similar to the Denisovan haplotype than any modern human haplotype. This mutation is seen at a high frequency in the Tibetan population, a low frequency in the Han population and is otherwise only seen in a sequenced Denisovan individual. This mutation must have been present before the Han and Tibetan populations diverged 2750 years ago.

 Source: https://en.wikipedia.org

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