High-altitude adaptation

High-altitude adaptation is an evolutionary modification in animals, most notably in birds and mammals, by which species are subjected to considerable physiological changes to survive in extremely high mountainous environments. As opposed to short-term adaptation, or more properly acclimatisation (which is basically an immediate physiological response to changing environment), the term "high-altitude adaptation" has strictly developed into the description of an irreversible, long-term physiological responses to high-altitude environments, associated with heritable behavioural and genetic changes. Perhaps, the phenomenon is most conspicuous, at least best documented, in human populations such as the Tibetans, the South Americans and the Ethiopians, who live in the otherwise uninhabitable high mountains of the Himalayas, Andes and Ethiopia respectively; and this represents one of the finest examples of natural selection in action.^[1]

Oxygen, essential for animal life, is proportionally abundant in the atmosphere with height from the sea level; hence, the highest mountain ranges of the world are considered unsuitable for habitation. Surprisingly, some 140 million people live permanently at high altitudes (>2,500 m) in North, Central and South America, East Africa, and Asia, and flourish very well for millennia in the exceptionally high mountains, without any apparent complications.^[2] This has become a recognised instance of the process of Darwinian evolution in humans acting on favourable characters such as enhanced respiratory mechanisms.^[3][4] As a matter of fact, this adaptation is so far the fastest case of evolution in humans that is scientifically documented.^{[5][6][7][8][9]} Among animals only few mammals (such as yak, ibex, Tibetan gazelle, vicunas, llamas, mountain goats, etc.) and certain birds are known to have completely adapted to high-altitude environments.^[10]

These adaptations are an example of convergent evolution, with adaptations occurring simultaneously on three continents. Tibetan humans and Tibetan domestic dogs found the genetic mutation in both species, EPAS1. This mutation has not been seen in Andean humans, showing the effect of a shared environment on evolution<ref name="genetic convergence in the adaptation of dogs and humans.^[11]

In humans

At elevation higher than 8,000 metres (26,000 ft), which is called the "death zone" in mountaineering, the available oxygen in the air is so low that it is considered insufficient to support life. Altitudes higher than 7,600 m (slightly less than 25,000 feet) are seriously lethal.^[3] Yet, there are Tibetans, Ethiopians and Americans who habitually live at places higher than 2,500 m from the sea level. For normal human population, even a brief stay at these places means mountain sickness, which is a syndrome of hypoxia or severe lack of oxygen, with complications such as fatigue, dizziness, breathlessness, headaches, insomnia, malaise, nausea, vomiting, body pain, loss of appetite, ear-ringing, blistering and purpling and of the hands and feet, and dilated veins.^[12] Amazingly for the native highlanders, there are no adverse effects; in fact, they are perfectly normal in all respects. Basically, the physiological and genetic adaptations in these people involve massive modification in the oxygen transport system of the blood, especially molecular changes in the structure and functions hemoglobin, a protein for carrying oxygen in the body.^[13][14] This is to compensate for perpetual low oxygen environment. This adaptation is associated with better developmental patterns such as high birth weight, increased lung volumes, increased breathing, and higher resting metabolism.^[15][16]

Genetic basis

Genome sequence of Tibetans in 2010 provide the first definitive clue to the molecular evolution of high-altitude adaptation. Genes such as EPAS1, PPARA and EGLN1 are found to have significant molecular changes among the Tibetans, and the genes are involved in haemoglobin production.^[5][17] These genes function in concert with another gene named hypoxia inducible factors (HIF), which in turn is a principal regulator of red blood cell production in response to oxygen metabolism.^[18] 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.^[19] Among the Andeans, there are no significant associations between EPAS1 or EGLN1 and haemoglobin concentration, indicating variation in the pattern of molecular adaptation.^[20] However, EGLN1 appears to be the principal signature of evolution, as it shows evidence of positive selection in both Tibetans and Andeans.^[21] Adaptive mechanism is still more different among the Ethiopian highlanders. Genomic analysis of two ethnic groups, Amhara and Oromo, revealed that gene variations associated with haemoglobin difference among Tibetans or other variants at the same gene location do not influence the adaptation in Ethiopians.^[22] Instead, several genes appear to be involved in Ethiopians, including CBARA1, VAV3, ARNT2 and THRB, which are known to play a role in HIF genetic functions.^[23]

The EPAS1 mutation in the Tibetan population has been linked to Denisovan or denisovan-related population<ref name="Altitude adaptation in tibetans caused by introgression of denisovan-like DNA.^[24] 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. ^[24]

In other mammals

Other mammals are also known to strive normally at high altitude and exhibit a striking number of adaptations in terms of morphology, physiology and behaviour. The Tibetan Plateau has very few mammalian species, ranging from wolf, kiang (Tibetan wild ass), goas, chiru (Tibetan antelope), wild yak, snow leopard, Tibetan sand fox, ibex, gazelle, Himalayan brown bear and water buffalo.^[25][26][27] These mammals can be broadly categorised based on their adaptability in high altitude into two broad groups, namely eurybarc and stenobarc. Those that can survive a wide range of high-altitude regions are eurybarc and include yak, ibex, Tibetan gazelle of the Himalayas and vicuñas llamas of the Andes. Stenobarc includes those with lesser ability to endure a range of differences in altitude, such as rabbits, mountain goats, sheep, and cats. Among domesticated animals, yaks are perhaps the highest dwelling animals. The wild herbivores of the Himalayas such as the Himalayan tahr, morkhor and chamois are of particularly interesting because of their ecological versatility and tolerance.^[28]

Yak adaptation

Domestic yak at Yamdrok Lake

Among domesticated animals, yaks (Bos grunniens) are the highest dwelling animals of the world, living at 3,000–5,000 metres (9,800–16,400 ft). The yak is the most important domesticated animal for Tibet highlanders in Qinghai Province of China, as the primary source of milk, meat and fertilizer. Unlike other yak or cattle species, which suffer from hypoxia in the Tibetan Plateau, the Tibetan domestic yaks thrive only at high altitude, and not at lowlands. Their physiology is well-adapted to high altitudes, with proportionately larger lungs and heart than other cattle, as well as greater capacity for transporting oxygen through their blood.^[29] In yaks, hypoxia-inducible factor 1 (HIF-1) has high expression in the brain, lung, and kidney, showing that it plays an important role in the adaptation to low oxygen environment.^[30] On 1 July 2012 the complete genomic sequence and analyses of a female domestic yak was announced, providing important insights into understanding mammalian divergence and adaptation at high altitude. Distinct gene expansions related to sensory perception and energy metabolism were identified.^[31] In addition, researchers also found an enrichment of protein domains related to the extracellular environment and hypoxic stress that had undergone positive selection and rapid evolution. For example, they found three genes that may play important roles in regulating the bodyʼs response to hypoxia, and five genes that were related to the optimisation of the energy from the food scarcity in the extreme plateau. One gene in particular, ADAM-17, is known to be involved in regulating response to low oxygen levels that is also found in Tibetan highlanders.^[32][33]

Mice adaptation

The deer mouse

The deer mouse (Peromyscus maniculatus) is the best studied species, other than humans, in terms of high-altitude adaptation.^[10] The deer mouse native to Andes highlands (up to 3,000 m) are found to have relatively low content of haemoglobin.^[34] Measurement of food intake, gut mass, and cardiopulmonary organ mass indicated proportional increase in mice living at high altitudes, which in turn show that life at high altitudes demands higher levels of energy.^[35] Variations in the globin genes (α and β-globin) seem to be the basis for increased oxygen-affinity of the haemoglobin and faster transport of oxygen.^[36][37] Structural comparisons show that in contrast to normal haemoglobin, the deer mouse haemoglobin lacks the hydrogen bond between α1Trp14 in the A helix and α1Thr67 in the E helix owing to the Thr67Ala substitution; and there is a unique hydrogen bond at the α1β1 interface between residues α1Cys34 and β1Ser128.^[38] The Peruvian native species of mice (Phyllotis andium and Phyllotis xanthopygus) have adapted to high Andes by using proportionately more carbohydrates and have higher oxidative capacities of cardiac muscles compared to closely related low-altitude (100–300 m) native species (Phyllotis amicus and Phyllotis limatus). This shows that highland mice have evolved a metabolic process to economise oxygen usage for physical activities in the hypoxic conditions.^[39]

In birds

Adaptation to high altitude has fascinated ornithologists for decades, but only a small proportion of high-altitude species have been studied. In Tibet, only few birds are found (28 endemic species), including, cranes, vultures, hawks, jays and geese.^[25][27][40] The Andes is quite rich in bird diversity. The Andean condor, the largest bird of its kind in the Western Hemisphere, occurs throughout much of the Andes but generally in very low densities; species of tinamous (notably members of the genus Nothoprocta), Andean goose, giant coot, Andean flicker, diademed sandpiper-plover, miners, sierra-finches and diuca-finches are also found in the highlands.^[41]

Cinnamon teal adaptation

Male cinnamon teal

Evidence for adaptation is best investigated among the Andean birds. The water fowls and cinnamon teal (Anas cyanoptera) are found to have undergone significant molecular modifications. It is now known that the α-haemoglobin subunit gene is highly structured between elevations among cinnamon teal populations, which involves almost entirely a single non-synonymous amino acid substitution at position 9 of the protein, with asparagine present almost exclusively within the low-elevation species, and serine in the high-elevation species. This implies important functional consequences for oxygen affinity.^[42] In addition, there is strong divergence in body size in the Andes and adjacent lowlands. These changes have shaped distinct morphological and genetic divergence within South American cinnamon teal populations.^[43]

Ground tit adaptation

In 2013, the molecular mechanism of high-altitude adaptation was elucidated in the Tibetan ground tit (Pseudopodoces humilis) using a draft genome sequence. Gene family expansion and positively selected gene analysis revealed genes that were related to cardiac function in the ground tit. Some of the genes identified to have positive selection include ADRBK1 and HSD17B7, which are involved in the adrenaline response and steroid hormone biosynthesis. Thus, the strengthened hormonal system is an adaptation strategy of this bird.^[44]

In other animals

An alpine Tibet hosts a limited diversity of animal species, of which snakes are common; and a notable species is the high-altitude jumping spider, that can live at over 6,500 metres (21,300 ft) of elevation.^[25] There are only 2 endemic reptiles and 10 endemic amphibians in the Tibet highlands.^[40] Gloydius himalayanus is perhaps the geographically highest living snake in the world, living at as high as 4,900 m in the Himalayas.^[45]

See also

• Altitude
• Organisms at high altitude
• Tibetan Plateau
• Fauna of the Andes
• Ethiopian Highlands

References

External links