High-altitude adaptation in humans

High-altitude adaptation in humans is an instance of

long-term physiological responses to high-altitude environments associated with heritable behavioral and genetic changes. 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.^[2]^[3]

Around 81.6 million humans (approximately 1.1% of the world's human population) live permanently at altitudes above 2,500 meters (8,200 sf),^[4] putting these populations at risk for chronic mountain sickness (CMS).^[1] However, the high-altitude populations in South America, East Africa, and South Asia have done so for millennia without apparent complications.^[5] This special adaptation is now recognized as an example of natural selection in action.^[6] The adaptation of the Tibetans is the fastest known example of human evolution, as it is estimated to have occurred around 1,000 BCE.^[7]^[8]^[9] to 7,000 BCE.^[10]^[11]

Origin and Basis

Himalayas, on the southern rim of the Tibetan Plateau

blistering and purpling of the hands and feet, and dilated blood vessels.^[14]^[15]^[16]

The sickness is compounded by related symptoms such as

seizures, or death of the mother.^[2]^[21]

An estimated 81.6 million humans live at an elevation higher than 2,500 meters (8,200 ft) above sea level, of which 21.7 million reside in Ethiopia, 12.5 million in China, 11.7 million in Colombia, 7.8 million in Peru, and 6.2 million in Bolivia.^[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.^[5]^[14] It is estimated that at 4,000 meters (13,000 ft), every lungful of air only has 60% of the oxygen molecules that humans at sea level have.^[22] Highlanders are thus constantly exposed to a low oxygen environment, yet they live without any debilitating problems.^[23] One of the best-documented effects of high altitude is a progressive reduction in birth weight. It has been known that women of the long-resident, high-altitude population are not affected. These women are known to give birth to heavier-weight infants than women of lowland inhabitants. This is particularly true among Tibetan babies, whose average birth weight is 294–650 (~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.^[25]^[26] Paul T. Baker, Penn State University, (in the Department of Anthropology) also conducted a considerable amount of research into human adaptation to high altitudes, and mentored students who continued this research.^[27] One of these students, anthropologist Cynthia Beall of Case Western Reserve University, began conducting research on high altitude adaptation among the Tibetans in the early 1980s, research which has continued for decades.^[28]

Physiological Basis

Tibetans

In the early 20th century, researchers observed the impressive physical abilities of Tibetans during Himalayan climbing expeditions. They considered the possibility that these abilities resulted from an evolutionary genetic adaptation to high-altitude conditions.

Tibetan plateau has an average elevation of 4,000 meters (13,000 ft) above sea level and covering more than 2.5 million km², it is the highest and largest plateau in the world. In 1990, it was estimated that 4,594,188 Tibetans live on the plateau, with 53% living at an altitude over 3,500 meters (11,500 ft). Fairly large numbers (approximately 600,000) live at an altitude exceeding 4,500 meters (14,800 ft) in the Chantong-Qingnan area.^[30]

Where the Tibetan highlanders live, the oxygen level is only about 60% of that at sea level.

The Tibetans, who have been living in the Chantong-Qingnan area for 3,000 years, do not exhibit the elevated hemoglobin concentrations to cope with oxygen deficiency as observed in other populations who have moved temporarily or permanently at high altitudes. Instead, the Tibetans inhale more air with each breath and breathe more rapidly than either sea-level populations or Andeans. Tibetans have better

exercise. 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.^[31]^[32]

With the proper physical preparation, individuals can develop short-term tolerance to high-altitude conditions. However, these biological changes are temporary and will reverse upon returning to lower elevations.[33] Moreover, while lowland people typically experience increased breathing for only a few days after entering high altitudes, Tibetans maintain this rapid breathing and elevated lung capacity throughout their lifetime.^[34] This enables them to inhale large amounts of air per unit of time to compensate for low oxygen levels. Additionally, Tibetans typically have significantly higher levels of nitric oxide in their blood, often double that of lowlanders. This likely contributes to enhanced blood circulation by promoting dilate in their blood vessels.^[35]

Furthermore, their hemoglobin level is not significantly different (average 15.6 g/dl in males and 14.2 g/dl in females)^[36] from those of humans living at low altitude. This is evidenced by mountaineers experiencing an increase of over 2 g/dl in hemoglobin levels within two weeks at the Mt. Everest base camp.^[37]) Consequently, Tibetans demonstrate the capacity to mitigate the effects of hypoxia and mountain sickness throughout their lives. 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.^[38]

Andeans

In contrast to the Tibetans, who have lived at high altitudes for no more than 11,000 years, the Andean highlanders show different patterns of hemoglobin adaptation. Their hemoglobin concentration is higher than those of the lowlander population, which also happens to lowlanders moving to high altitudes. When they spend some weeks in the lowlands, their hemoglobin drops to the average of other humans. This shows only temporary and reversible acclimatization. However, in contrast to lowland people, they have increased oxygen levels in their hemoglobin, that is, more oxygen per blood volume than other humans. This confers an ability to carry more oxygen in each red blood cell, making a more effective transport of oxygen in their body while their breathing is at the same rate.

red blood cells. Though the physical growth in body size is delayed, change in lung volumes is accelerated.^[40]

An incomplete adaptation such as elevated hemoglobin levels still leaves Andeans at risk for mountain sickness with old age.

Among the Quechua people of the

endothelial nitric oxide synthase, eNOS), which is associated with higher levels of nitric oxide in high altitude.^[41] Nuñoa children of Quechua ancestry exhibit higher blood-oxygen content (91.3) and lower heart rate (84.8) than their counterpart school children of different ethnicity, who have an average of 89.9 blood-oxygen and 88–91 heart rate.^[42] Born and raised Quechua women have comparatively enlarged lung volume for increased respiration.^[43]

Bolivian Aymara people, the resting ventilation and hypoxic ventilatory response were quite low (roughly 1.5 times lower), in contrast to those of the Tibetans. The intrapopulation genetic variation was relatively less among the Aymara people.^[46]^[47] Moreover, when compared to Tibetans, the blood hemoglobin level at high altitudes among Aymaran is notably higher, with an average of 19.2 g/dl for males and 17.8 g/dl for females.^[36] Among the different native highlander populations, the underlying physiological responses to adaptation differ. 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.^[48] Methylation also influences oxygenation.^[49]

Ethiopians

The people of the

Ethiopian highlands also live at extremely high altitudes, around 3,000 meters (9,800 ft) to 3,500 meters (11,500 ft). Highland Ethiopians exhibit elevated hemoglobin levels, like Andeans and lowlander humans at high altitudes, but do not exhibit the Andeans’ increase in oxygen content of hemoglobin.^[50] Among healthy individuals, the average hemoglobin concentrations are 15.9 and 15.0 g/dl for males and females, respectively (which is lower than normal, almost similar to the Tibetans), and an average oxygen saturation of hemoglobin is 95.3% (which is higher than average, like the Andeans).^[51] Additionally, Ethiopian highlanders do not exhibit any significant change in blood circulation of the brain, which has been observed among the Peruvian highlanders (and attributed to their frequent altitude-related illnesses).^[52] Yet, similar to the Andeans and Tibetans, the Ethiopian highlanders are immune to the extreme dangers posed by high-altitude environment, and their pattern of adaptation is definitely unique from that of other highland people.^[22]

Genetic Basis

The underlying molecular evolution of high-altitude adaptation has been explored in recent years.^[23] Depending on the geographical and environmental pressures, high-altitude adaptation involves different genetic patterns, some of which have evolved not long ago. For example, Tibetan adaptations became prevalent in the past 3,000 years, a rapid example of recent human evolution. At the turn of the 21st century, it was reported that the genetic makeup of the respiratory components of the Tibetan and the Ethiopian populations were significantly different.^[48]