High-altitude adaptation in humans
While the rest of the human population would suffer serious health consequences at high altitudes, the indigenous inhabitants of these regions thrive in the highest parts of the world.
These humans have undergone extensive physiological and genetic changes, particularly in the regulatory systems of oxygen respiration and blood circulation when compared to the general lowland population.
[13] Symptoms include fatigue, dizziness, breathlessness, headaches, insomnia, malaise, nausea, vomiting, body pain, loss of appetite, ear-ringing, blistering and purpling of the hands and feet, and dilated blood vessels.
[17][18] Over a span of multiple days, individuals experiencing the effects of high-altitude hypoxia demonstrate raised respiratory activity and elevated metabolic conditions which persist during periods of rest.
[19][20] In women, pregnancy can be severely affected, such as development of preeclampsia, which causes premature labor, low birth weight of babies, and often complicates with profuse bleeding, seizures, or death of the mother.
[4] Certain natives of Tibet, Ethiopia, and the Andes have been living at these high altitudes for generations and are resistant to hypoxia as a consequence of genetic adaptation.
This is particularly true among Tibetan babies, whose average birth weight is 294–650g (~470) g heavier than the surrounding Chinese population, and their blood-oxygen level is considerably higher.
[24] Scientific investigation of high-altitude adaptation was initiated by A. Roberto Frisancho of the University of Michigan in the late 1960s among the Quechua people of Peru.
[27] One of these students, anthropologist Cynthia Beall of Case Western Reserve University, began conducting decades-long research on high altitude adaptation among the Tibetans in the early 1980s.
For example, among four quantitative features, such as resting ventilation, hypoxic ventilatory response, oxygen saturation, and hemoglobin concentration, the levels of variations are significantly different between the Tibetans and the Aymaras.
[32] Tibetans who have been living in the Chantong-Qingnan area for 3,000 years do not exhibit the same elevated hemoglobin concentrations to cope with oxygen deficiency that are observed in other populations who have moved temporarily or permanently to high altitudes.
They show a sustained increase in cerebral blood flow, lower hemoglobin concentration, and less susceptibility to chronic mountain sickness than other populations due to their longer history of high-altitude habitation.
Even when ascending extraordinarily high peaks such as Mount Everest, they exhibit consistent oxygen uptake, heightened ventilation, augmented hypoxic ventilatory responses, expanded lung volumes, increased diffusing capacities, stable body weight, and improved sleep quality compared to lowland populations.
[45][46] Among the Bolivian Aymara people, the resting ventilation and hypoxic ventilatory response were quite low (roughly 1.5 times lower) compared to those of the Tibetans.
[23] Depending on geographical and environmental pressures, high-altitude adaptation involves different genetic patterns, some of which have evolved not long ago.
Initially, the strongest signal of natural selection was a transcription factor involved in response to hypoxia, called endothelial Per-Arnt-Sim (PAS) domain protein 1 (EPAS1).
It was found that one single-nucleotide polymorphism (SNP) at EPAS1 shows a 78% frequency difference between Tibetan and mainland Chinese samples, representing the fastest genetic change observed in any human gene to date.
EPAS1 is significantly associated with increased lactate concentration, a product of anaerobic glycolysis, and PPARA is correlated with decrease in the activity of fatty acid oxidation.
[68][69] This suggests that selection in Andeans, instead of targeting the HIF pathway like in the Tibetans, focused on adaptations of the cardiovascular system to combat chronic disease at high altitude.
Analysis of ancient Andean genomes, some dating back 7,000 years, discovered selection in DST, a gene involved in cardiovascular function.
[70] The whole genome sequences of 20 Andeans (half of them having chronic mountain sickness) revealed that two genes, SENP1 (an erythropoiesis regulator) and ANP32D (an oncogene) play vital roles in their weak adaptation to hypoxia.
This supports the hypothesis that adaptation to high altitude arose independently among different highlander populations as a result of convergent evolution.
