Studies of high-altitude residents have greatly contributed to our understanding of physiological adaptation. As you’d expect, altitude studies have focused on inhabitants of mountainous regions, particularly in the Himalayas, Andes, and Rocky Mountains. Of these three areas, the Himalayas probably have the longest history of permanent human habitation (Moore et al., 1998). Today perhaps as many as 25 million people live at altitudes above 10,000 feet. In Tibet, permanent settlements exist above 15,000 feet; in the Andes. they can be found as high as 17,000 feet Because the mechanisms that maintain homeostasis in humans evolved at lower altitudes, we’re compromised by the conditions at higher elevations. At high altitudes, many factors result in stress on the human body. These include hypoxia, more intense solar radiation, cold temperatures, low humidity, wind (which amplifies cold stress), a reduced nutritional base, and rough terrain. Of these, hypoxia causes the most problems for human physiological functions, especially those involving the heart, lungs, and brain.
Hypoxia is caused by reduced barometric pressure. It’s not that there’s less oxygen in the atmosphere at high altitudes; rather, it’s less concentrated. Therefore to obtain the same amount of oxygen at 9,000 feet as at sea level, people must make certain physiological alterations that increase the body’s ability to transport and efficiently use the oxygen that’s available.
Reproduction in particular is affected through increased infant mortality rates, miscarriage, low birth weights, and premature births. One cause of fetal and maternal death is preeclampsia, a severe elevation of blood pressure in pregnant women after the 20th gestational week. In another study of Colorado residents, Palmer and colleagues (1999) reported that among pregnant women living at elevations over 10,000 feet, the prevalence of preeclampsia was 16 percent, compared with 3 percent at around 4,000 feet. In general, the problems related to childbearing are attributed to issues that compromise the vascular supply (and thus oxygen transport) to the fetus.
People born at lower altitudes and high-altitude natives differ somewhat in how they adapt to insufficient amounts of available oxygen. When people born at low elevations travel to higher ones, the process of acclimatization begins within a day or two. These changes include increases in metabolic rate, respiration, heart rate, and the production of red blood cells. (Red blood cells contain hemoglobin, the protein responsible for transporting oxygen to organs and tissues.)
In high-altitude natives, acclimatization occurs during growth and development. This type of developmental acclimatization is present only in people who grow up in high-altitude areas, not in those who moved there as adults. Compared with populations at lower elevations, lifelong residents of high altitude grow somewhat more slowly and mature later. Other differences include greater lung and heart capacity. People born at high altitudes are also more efficient than migrants at diffusing oxygen from blood to body tissues, and the genes that regulate this ability are beginning to be identified. Developmental acclimatization to high altitude serves as a good example of physiological flexibility by illustrating how, within the limits set by genetic factors, development can be influenced by environmental factors.
But the best evidence for permanent high-altitude adaptation is provided by the indigenous peoples of Tibet, who have inhabited regions higher than 12,000 feet for at least 7,000 (Simonson et al., 2010) and perhaps as long as 25,000 years. For this reason, these populations have been the subject of many studies. Altitude does not negatively affect reproduction in highland Tibetans to the degree it does in other populations. Infants have birth weights as high as those of lowland Tibetan groups and higher than those of recent (20 to 30 years) Chinese immigrants. This fact may be the result of alterations in maternal blood flow to the uterus during pregnancy (Moore et al., 2006).
Another line of evidence concerns how the body processes glucose (blood sugar). Glucose is critical because it’s the only source of energy used by the brain, and it’s also used, although not exclusively, by the heart. Both highland Tibetans and the Quechua (inhabitants of high-altitude regions of the Peruvian Andes) burn glucose in a way that permits more efficient oxygen use. This implies the presence of genetic mutations in the mitochondrial DNA, because mtDNA directs how cells process glucose. It also indicates that natural selection has acted to increase the frequency of these advantageous mutations in these groups.
We now have solid evidence that natural selection has acted strongly and rapidly to increase the frequency of certain alleles that have produced adaptive responses to altitude in Tibetans. Ninety percent of Tibetan highlanders possess a point mutation in a gene called EPAS1, which is involved in red blood cell production. In effect, the EPAS1 mutation inhibits the increased red blood cell production we would expect to see in people living at high altitude. Thus Tibetans have red cell counts similar to those of populations living at sea level. Interestingly, the Quechua and other high-altitude residents of the Andes do not have this mutation and have elevated red cell counts compared with lowland inhabitants. But if increased red blood cell production is advantageous at high altitude, why would selection favor a mutation that acts against it in Tibetans? The answer is that beyond certain levels, elevated numbers of red cells can actually “thicken” the blood and lead to increased risk of stroke, blood clots, and heart attack. In pregnant women, they can also lead to impaired fetal growth and even fetal death. Thus, although the mechanisms aren’t yet understood, Tibetans have acquired a number of genetically influenced adaptations to hypoxic conditions while still producing the same amount of hemoglobin we would expect at sea level. This mutation is believed to have appeared only around 4,000 ya, yet it is present throughout most highland Tibetan populations. The fact that it has spread so rapidly indicates that it is extremely advantageous and that natural selection has acted very powerfully and quickly to increase its frequency (Yi et al., 2010).