High-altitude adaptation in humans is an instance of
evolutionary modification in certain human populations, including those of
Tibet
Tibet (; ''Böd''; ), or Greater Tibet, is a region in the western part of East Asia, covering much of the Tibetan Plateau and spanning about . It is the homeland of the Tibetan people. Also resident on the plateau are other ethnic groups s ...
in Asia, the
Andes
The Andes ( ), Andes Mountains or Andean Mountain Range (; ) are the List of longest mountain chains on Earth, longest continental mountain range in the world, forming a continuous highland along the western edge of South America. The range ...
of the Americas, and
Ethiopia
Ethiopia, officially the Federal Democratic Republic of Ethiopia, is a landlocked country located in the Horn of Africa region of East Africa. It shares borders with Eritrea to the north, Djibouti to the northeast, Somalia to the east, Ken ...
in Africa, who have evolved the ability to survive at
altitudes
Altitude is a distance measurement, usually in the vertical or "up" direction, between a reference datum and a point or object. The exact definition and reference datum varies according to the context (e.g., aviation, geometry, geographical s ...
above 2,500 meters (8,200 ft).
This adaptation means irreversible,
long-term physiological responses to high-altitude environments associated with heritable
behavioral
Behavior (American English) or behaviour (British English) is the range of actions of individuals, organisms, systems or artificial entities in some environment. These systems can include other systems or organisms as well as the inanimate p ...
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.
Around 81.6 million humans (approximately 1.1% of the world's human population) live permanently at
altitude
Altitude is a distance measurement, usually in the vertical or "up" direction, between a reference datum (geodesy), datum and a point or object. The exact definition and reference datum varies according to the context (e.g., aviation, geometr ...
s above 2,500 meters (8,200 ft),
which would seem to put these populations at risk for
chronic mountain sickness (CMS).
However, the high-altitude populations in South America,
East Africa
East Africa, also known as Eastern Africa or the East of Africa, is a region at the eastern edge of the Africa, African continent, distinguished by its unique geographical, historical, and cultural landscape. Defined in varying scopes, the regi ...
, and
South Asia
South Asia is the southern Subregion#Asia, subregion of Asia that is defined in both geographical and Ethnicity, ethnic-Culture, cultural terms. South Asia, with a population of 2.04 billion, contains a quarter (25%) of the world's populatio ...
have lived there for
millennia
A millennium () is a period of one thousand years, one hundred decades, or ten centuries, sometimes called a kiloannum (ka), or kiloyear (ky). Normally, the word is used specifically for periods of a thousand years that begin at the starting p ...
without apparent complications.
This special
adaptation
In biology, adaptation has three related meanings. Firstly, it is the dynamic evolutionary process of natural selection that fits organisms to their environment, enhancing their evolutionary fitness. Secondly, it is a state reached by the p ...
is now recognized as an example of
natural selection
Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
in action.
The adaptation of the Tibetans is the fastest known example of
human evolution
''Homo sapiens'' is a distinct species of the hominid family of primates, which also includes all the great apes. Over their evolutionary history, humans gradually developed traits such as Human skeletal changes due to bipedalism, bipedalism, de ...
, as it is estimated to have occurred between 1,000 BCE
to 7,000 BCE.
Origin and basis
Humans
Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...
are generally adapted to
lowland
Upland and lowland are conditional descriptions of a plain based on elevation above sea level. In studies of the ecology of freshwater rivers, habitats are classified as upland or lowland.
Definitions
Upland and lowland are portions of a ...
environments where oxygen is abundant.
At altitudes above , such humans experience
altitude sickness
Altitude sickness, the mildest form being acute mountain sickness (AMS), is a harmful effect of high altitude, caused by rapid exposure to low amounts of oxygen at high elevation. People's bodies can respond to high altitude in different wa ...
, which is a type of
hypoxia, a clinical syndrome of severe lack of oxygen. Some humans develop the illness beginning at above 1,500 meters (5,000 ft). Symptoms include
fatigue
Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself.
Fatigue (in the medical sense) is sometimes associated wit ...
,
dizziness
Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to Balance disorder, disequilibrium or a non-specific feeling, such as giddiness or foolishness.
Dizziness is a ...
,
breathlessness,
headaches
A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Head ...
,
insomnia
Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...
,
malaise
In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...
,
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat.
Over 30 d ...
,
vomiting
Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...
,
body pain,
loss of appetite
Anorexia is a medical term for a loss of appetite. While the term outside of the scientific literature is often used interchangeably with anorexia nervosa, many possible causes exist for a loss of appetite, some of which may be harmless, while o ...
,
ear-ringing,
blistering and
purpling of the hands and feet, and
dilated blood vessels.
The sickness is compounded by related symptoms such as
cerebral oedema (swelling of brain) and
pulmonary oedema (fluid accumulation in lungs) . 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. Subsequently, afflicted people will experience slowly declining heart rate. Hypoxia is a primary contributor to fatalities within mountaineering groups, making it a significant risk factor within high-altitude related challenges. In women, pregnancy can be severely affected, such as development of
preeclampsia
Pre-eclampsia is a multi-system disorder specific to pregnancy, characterized by the new onset of high blood pressure and often a significant amount of protein in the urine or by the new onset of high blood pressure along with significant end- ...
, which causes
premature labor
Preterm birth, also known as premature birth, is the Childbirth, birth of a baby at fewer than 37 weeks Gestational age (obstetrics), gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 ...
,
low birth weight of babies, and often
complicates with
profuse bleeding,
seizures
A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...
, or
death of the mother.
An estimated 81.6 million humans live at an elevation higher than above sea level, of which 21.7 million reside in
Ethiopia
Ethiopia, officially the Federal Democratic Republic of Ethiopia, is a landlocked country located in the Horn of Africa region of East Africa. It shares borders with Eritrea to the north, Djibouti to the northeast, Somalia to the east, Ken ...
, 12.5 million in
China
China, officially the People's Republic of China (PRC), is a country in East Asia. With population of China, a population exceeding 1.4 billion, it is the list of countries by population (United Nations), second-most populous country after ...
, 11.7 million in
Colombia
Colombia, officially the Republic of Colombia, is a country primarily located in South America with Insular region of Colombia, insular regions in North America. The Colombian mainland is bordered by the Caribbean Sea to the north, Venezuel ...
, 7.8 million in
Peru
Peru, officially the Republic of Peru, is a country in western South America. It is bordered in the north by Ecuador and Colombia, in the east by Brazil, in the southeast by Bolivia, in the south by Chile, and in the south and west by the Pac ...
, and 6.2 million in
Bolivia
Bolivia, officially the Plurinational State of Bolivia, is a landlocked country located in central South America. The country features diverse geography, including vast Amazonian plains, tropical lowlands, mountains, the Gran Chaco Province, w ...
.
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.
It is estimated that at altitude, every lungful of air has approximately 60% of the oxygen molecules found in a lungful of air at sea level. Highlanders are thus constantly exposed to a low oxygen environment, yet they live without any debilitating problems.
One of the best-documented effects of high altitude on non-adapted women is a progressive reduction in birth weight
Birth weight is the body weight of a baby at their birth. The average birth weight in babies of European and African descent is , with the normative range between .
15% of babies born in 2012 had a low birth weight and 14.7% in 2020. It is pro ...
. By contrast, the women of long-resident, high-altitude populations are known to give birth to heavier-weight infants than women of the lowland. 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.
Scientific investigation of high-altitude adaptation was initiated by A. Roberto Frisancho of the University of Michigan
The University of Michigan (U-M, U of M, or Michigan) is a public university, public research university in Ann Arbor, Michigan, United States. Founded in 1817, it is the oldest institution of higher education in the state. The University of Mi ...
in the late 1960s among the Quechua people
Quechua people (, ; ) , Quichua people or Kichwa people may refer to any of the Indigenous peoples of South America who speak the Quechua languages, which originated among the Indigenous people of Peru. Although most Quechua speakers are nativ ...
of Peru. Paul T. Baker of Penn State University
The Pennsylvania State University (Penn State or PSU) is a Public university, public Commonwealth System of Higher Education, state-related Land-grant university, land-grant research university with campuses and facilities throughout Pennsyl ...
’
Department of Anthropology
also conducted a considerable amount of research into human adaptation to high altitudes, and mentored students who continued this research. One of these students, anthropologist Cynthia Beall of Case Western Reserve University
Case Western Reserve University (CWRU) is a Private university, private research university in Cleveland, Ohio, United States. It was established in 1967 by a merger between Western Reserve University and the Case Institute of Technology. Case ...
, began conducting decades-long research on high altitude adaptation among the Tibetans in the early 1980s.
Physiological basis
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. Methylation
Methylation, in the chemistry, chemical sciences, is the addition of a methyl group on a substrate (chemistry), substrate, or the substitution of an atom (or group) by a methyl group. Methylation is a form of alkylation, with a methyl group replac ...
also influences oxygenation.
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. The Tibetan plateau
The Tibetan Plateau, also known as the Qinghai–Tibet Plateau or Qingzang Plateau, is a vast elevated plateau located at the intersection of Central Asia, Central, South Asia, South, and East Asia. Geographically, it is located to the north of H ...
has an average elevation of above sea level and covers more than 2.5 million km2; it is the highest and largest plateau
In geology and physical geography, a plateau (; ; : plateaus or plateaux), also called a high plain or a tableland, is an area of a highland consisting of flat terrain that is raised sharply above the surrounding area on at least one side. ...
in the world. In 1990, it was estimated that 4,594,188 Tibetans live on the plateau, with 53% living at an altitude over . Fairly large numbers (approximately 600,000) live at an altitude exceeding in the Chantong-Qingnan area.
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. Instead, the Tibetans inhale more air with each breath and breathe more rapidly than either sea-level populations or Andeans. Tibetans have better oxygenation at birth, enlarged lung volumes throughout life, and a higher capacity for exercise
Exercise or workout is physical activity that enhances or maintains fitness and overall health. It is performed for various reasons, including weight loss or maintenance, to aid growth and improve strength, develop muscles and the cardio ...
. They show a sustained increase in cerebral blood flow, lower hemoglobin concentration, and less susceptibility to chronic mountain sickness
Chronic mountain sickness (CMS) is a disease in which the proportion of blood volume that is occupied by red blood cells increases (polycythaemia) and there is an abnormally low level of oxygen in the blood ( hypoxemia). CMS typically develops afte ...
than other populations due to their longer history of high-altitude habitation.
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. 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. 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
Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...
in their blood, often double that of lowlanders. This likely contributes to enhanced blood circulation by promoting vasodilation
Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wa ...
.
Furthermore, their hemoglobin level is not significantly different (average 15.6 g/dl in males and 14.2 g/dl in females) 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. 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.
Andeans
In contrast to the Tibetans, Andean highlanders show different patterns of hemoglobin adaptation. Their hemoglobin concentration is higher than those of the lowlander population, which also happens to lowlanders who move to high altitudes. When they spend some weeks in the lowlands, their hemoglobin drops to the same levels as lowland humans. However, in contrast to lowland humans, they have increased oxygen levels in their hemoglobin; that is, more oxygen per blood volume. This confers an ability to carry more oxygen in each red blood cell, meaning a more effective transport of oxygen throughout their bodies. This enables Andeans to overcome hypoxia and normally reproduce without risk of death for the mother or baby. They have developmentally-acquired enlarged residual lung volume and an associated increase in alveolar area, which are supplemented with increased tissue thickness and moderate increase in red blood cells
Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...
. Though Andean highlander children show delayed body growth, change in lung volume is accelerated.
Among the Quechua people of the Altiplano
The Altiplano (Spanish language, Spanish for "high plain"), Collao (Quechuan languages, Quechua and Aymara language, Aymara: Qullaw, meaning "place of the Qulla people, Qulla") or Andean Plateau, in west-central South America, is the most extens ...
, there is a significant variation in '' NOS3'' (the gene encoding endothelial nitric oxide synthase, eNOS), which is associated with higher levels of nitric oxide at high altitude. Nuñoa children of Quechua ancestry exhibit higher blood-oxygen content (91.3) and lower heart rate (84.8) than their peers of different ethnicities, who have an average of 89.9 blood-oxygen and 88–91 heart rate. Quechua women have comparatively enlarged lung volume for increased respiration.
Blood profile comparisons show that among the Andeans, Aymaran highlanders are better adapted to highlands than the Quechuas. Among the Bolivian
Bolivian may refer to:
* Something of, or related to, Bolivia
** Bolivian people
** Demographics of Bolivia
** Culture of Bolivia
* SS Bolivian, SS ''Bolivian'', later SS ''Alfios'', a British-built standard cargo ship
{{disambiguation ...
Aymara people, the resting ventilation and hypoxic ventilatory response were quite low (roughly 1.5 times lower) compared to those of the Tibetans. The intrapopulation genetic variation was relatively smaller among the Aymara people. Moreover, when compared to Tibetans, blood hemoglobin levels 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.[
]
Ethiopians
The people of the Ethiopian highlands
The Ethiopian Highlands (also called the Abyssinian Highlands) is a rugged mass of mountains in Ethiopia in Northeast Africa. It forms the largest continuous area of its elevation in the continent, with little of its surface falling below , whil ...
also live at extremely high altitudes, around to . 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. 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, similar to the Tibetans), and an average oxygen saturation of hemoglobin is 95.3% (which is higher than average, like the Andeans). 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. 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 unique from that of other highland people.
Genetic basis
The underlying molecular evolution
Molecular evolution describes how Heredity, inherited DNA and/or RNA change over evolutionary time, and the consequences of this for proteins and other components of Cell (biology), cells and organisms. Molecular evolution is the basis of phylogen ...
of high-altitude adaptation has been explored in recent years. Depending on 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, an example of rapid recent human evolution
Recent human evolution refers to evolutionary adaptation, Sexual selection, sexual and natural selection, and genetic drift within ''Human, Homo sapiens'' populations, since their separation and dispersal in the Middle Paleolithic about 50,000 ye ...
. 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.
Tibetans
Substantial evidence from Tibetan highlanders suggests that variation in hemoglobin and blood-oxygen levels are adaptive as Darwinian fitness. It has been documented that Tibetan women with a high likelihood of possessing one to two allele
An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule.
Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
s for high blood-oxygen content (which is rare in other women) had more surviving children; the higher the oxygen capacity, the lower the infant mortality. In 2010, for the first time, the genes responsible for the unique adaptive traits were identified following genome sequencing of 50 Tibetans and 40 Han Chinese
The Han Chinese, alternatively the Han people, are an East Asian people, East Asian ethnic group native to Greater China. With a global population of over 1.4 billion, the Han Chinese are the list of contemporary ethnic groups, world's la ...
from Beijing
Beijing, Chinese postal romanization, previously romanized as Peking, is the capital city of China. With more than 22 million residents, it is the world's List of national capitals by population, most populous national capital city as well as ...
. 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
Endothelial PAS domain-containing protein 1 (EPAS1, also known as hypoxia-inducible factor-2alpha (HIF-2α)) is a protein that is encoded by the ''EPAS1'' gene in mammals. It is a type of hypoxia-inducible factor, a group of transcription factor ...
''). It was found that one single-nucleotide polymorphism
In genetics and bioinformatics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a ...
(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. Hence, Tibetan adaptation to high altitude is recognized as one of the fastest processes of phenotypically observable evolution in humans, which is estimated to have occurred a few thousand years ago, when the Tibetans split from the mainland Chinese population. The time of genetic divergence has been variously estimated as 2,750 (original estimate), 4,725, 8,000, or 9,000 years ago.
Mutations
In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
in ''EPAS1'' occur at a higher frequency in Tibetans than their Han neighbors and correlates with decreased hemoglobin concentrations among the Tibetans. This is known as the hallmark of their adaptation to hypoxia. Simultaneously, two genes, egl nine homolog 1 ('' EGLN1''), which inhibits hemoglobin production under high oxygen concentration, and peroxisome proliferator-activated receptor alpha ('' PPARA''), were also identified to be positively selected for decreased hemoglobin levels in the Tibetans.
Similarly, the Sherpas
The Sherpa people () are one of the Nepalese ethnic groups native to the most mountainous regions of Nepal, India, and the Tibetan Autonomous Region of China.
The majority of Sherpas live in the eastern regions of Nepal, namely the Solukhum ...
, known for their Himalayan hardiness, exhibit similar patterns in the ''EPAS1'' gene, which is further evidence that the gene is under selection
Selection may refer to:
Science
* Selection (biology), also called natural selection, selection in evolution
** Sex selection, in genetics
** Mate selection, in mating
** Sexual selection in humans, in human sexuality
** Human mating strat ...
pressure for adaptation to the high-altitude life of Tibetans. A study in 2014 indicates that the mutant ''EPAS1
Endothelial PAS domain-containing protein 1 (EPAS1, also known as hypoxia-inducible factor-2alpha (HIF-2α)) is a protein that is encoded by the ''EPAS1'' gene in mammals. It is a type of hypoxia-inducible factor, a group of transcription factor ...
'' gene could have been inherited from archaic hominin
The Hominini (hominins) form a taxonomic tribe of the subfamily Homininae (hominines). They comprise two extant genera: ''Homo'' (humans) and '' Pan'' (chimpanzees and bonobos), and in standard usage exclude the genus '' Gorilla'' ( gorillas) ...
s, the Denisovans
The Denisovans or Denisova hominins ( ) are an extinct species or subspecies of archaic human that ranged across Asia during the Lower Paleolithic, Lower and Middle Paleolithic, and lived, based on current evidence, from 285 thousand to 25 thou ...
. ''EPAS1'' and ''EGLN1'' are believed to be important genes for unique adaptive traits when compared with those of the Chinese and Japanese. Comparative genome analysis in 2014 revealed that the Tibetans inherited an equal mixture of genomes from the Nepalese Sherpas and Hans, and that they acquired adaptive genes from the Sherpa lineage. Further, the population split was estimated to occur around 20,000 to 40,000 years ago, a range supported by archaeological, mitochondria DNA, and Y chromosome evidence for an initial colonization of the Tibetan plateau around 30,000 years ago.
The genes ''EPAS1'', ''EGLN1'', and ''PPARA'' function in concert with another gene named hypoxia inducible factors (''HIF''), which is in turn a principal regulator of red blood cell production (erythropoiesis
Erythropoiesis (from Greek ''erythro'', meaning ''red'' and ''poiesis'', meaning ''to make'') is the process which produces red blood cells (erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell.
It is s ...
) in response to oxygen metabolism. The genes are associated not only with decreased hemoglobin levels, but also with regulating metabolism. ''EPAS1'' is significantly associated with increased lactate concentration, a product of anaerobic glycolysis
Anaerobic glycolysis is the transformation of glucose to lactate when limited amounts of oxygen (O2) are available. This occurs in health as in exercising and in disease as in sepsis and hemorrhagic shock. providing energy for a period ranging fr ...
, and ''PPARA'' is correlated with decrease in the activity of fatty acid oxidation. ''EGLN1'' codes for an enzyme, prolyl hydroxylase 2 (PHD2), involved in erythropoiesis.
Among the Tibetans, a mutation in ''EGLN1'' (specifically at position 12, where cytosine is replaced with guanine; and at 380, where G is replaced with C) results in mutant PHD2 (aspartic acid at position 4 becomes glutamine, and cysteine at 127 becomes serine) and this mutation inhibits erythropoiesis. This mutation is estimated to have occurred approximately 8,000 years ago. 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
HLA-DQ (DQ) is a cell surface receptor protein found on antigen-presenting cells. It is an αβ heterodimer of type MHC class II. The α and β chains are encoded by two loci, HLA-DQA1 and HLA-DQB1, that are adjacent to each other on chro ...
'' and ''HLA-DR
HLA-DR is an MHC class II cell surface receptor encoded by the human leukocyte antigen complex on chromosome 6 region 6p21.31. The complex of HLA-DR (Human Leukocyte Antigen – DR isotype) and peptide, generally between 9 and 30 amino acids in l ...
'' gene clusters) and biological process categories of response to DNA damage
DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...
stimulus and DNA repair
DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...
(such as ''RAD51
DNA repair protein RAD51 homolog 1 is a protein encoded by the gene ''RAD51''. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to t ...
'', '' 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.
Andeans
The patterns of genetic adaptation among the Andeans are largely distinct from those of the Tibetans, with both populations showing evidence of positive natural selection in different genes or gene regions. For genes in the HIF pathway, ''EGLN1'' is the only instance where evidence of positive selection is observed in both Tibetans and Andeans. Even then, the pattern of variation for this gene differs between the two populations. Furthermore, there are no significant associations between ''EPAS1'' or ''EGLN1'' SNP genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
s and hemoglobin concentration among the Andeans, which is characteristic of the Tibetans.
The Andean pattern of adaptation is characterized by selection in a number of genes involved in cardiovascular development and function (such as BRINP3, EDNRA, NOS2A). 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. 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.
Ethiopians
The adaptive mechanism of Ethiopian highlanders differs from those of the Tibetans and Andeans due to the fact that their migration to the highland was relatively early. For example, the Amhara have inhabited altitudes above for at least 5,000 years and altitudes around to for more than 70,000 years. Genomic analysis of two ethnic groups, Amhara and Oromo, has revealed that gene variations associated with hemoglobin difference among Tibetans or other variants at the exact gene location do not influence the adaptation in Ethiopians. Several candidate genes have been identified as possible explanations for the adaptation of Ethiopians, including '' CBARA1'', ''VAV3
Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the ''VAV3'' gene.
This gene is a member of the VAV gene family. The VAV proteins are guanine nucleotide exchange factors (GEFs) for Rho family GTPases that activ ...
'', '' ARNT2'' and '' THRB''. Two of these genes (''THRB'' and ''ARNT2'') are known to play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. This supports the hypothesis that adaptation to high altitude arose independently among different highlander populations as a result of convergent evolution
Convergent evolution is the independent evolution of similar features in species of different periods or epochs in time. Convergent evolution creates analogous structures that have similar form or function but were not present in the last comm ...
.
See also
* Altitude
Altitude is a distance measurement, usually in the vertical or "up" direction, between a reference datum (geodesy), datum and a point or object. The exact definition and reference datum varies according to the context (e.g., aviation, geometr ...
* Effects of high altitude on humans
The effects of high altitude on humans are mostly the consequences of reduced partial pressure of oxygen in the atmosphere. The medical problems that are direct consequence of high altitude are caused by the low inspired partial pressure of oxyge ...
(including acclimatisation
Acclimatization or acclimatisation ( also called acclimation or acclimatation) is the process in which an individual organism adjusts to a change in its environment (such as a change in altitude, temperature, humidity, photoperiod, or pH), ...
)
* High-altitude adaptation
Organisms can live at high altitude, either on land, in water, or while flying. Decreased oxygen availability and decreased temperature make life at such altitudes challenging, though many species have been successfully adapted via considerable ...
* High-altitude football controversy
* Tibetan Plateau
The Tibetan Plateau, also known as the Qinghai–Tibet Plateau or Qingzang Plateau, is a vast elevated plateau located at the intersection of Central Asia, Central, South Asia, South, and East Asia. Geographically, it is located to the north of H ...
References
External links
Adapting to High Altitude
High Altitude and Cold: Adaptation to the extremes
* ttps://www.bbc.co.uk/nature/adaptations/High_altitude BBC: Altitude tolerantbr>Understanding Evolution: The mysteries of Tibet
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Mountaineering and health
Respiratory physiology
Human evolution
Anthropology
Evolutionary biology