Human Altitude Evolution

An interesting comment on quirks and quarks this week inspired me to do a little research on the adaptations to high altitude in different human populations. The evolution of human traits in response to high altitude environments differs between different populations. There are the legendary Tibetan highlanders of the Himalayas but there are also physiological adaptations of human populations in the Andes and in the Amhara of Ethiopia. Interestingly we also know the genetic basis for these adaptations through comparative genomics.
High altitude environments present many challenges for human physiology. These challenges are due to the thin air at higher elevations. The partial pressure of oxygen decreases with air pressure and air pressure decreases exponentially with altitude. Air pressure is half of sea-level air pressure at 5000m. This decreased availability of oxygen at higher altitudes, or hypoxia, causes altitude sickness and potentially fatal high altitude pulmonary edema and high altitude cerebral edema. The frequency of these conditions and others increase with increasing altitude.
Mere mortal lowlanders are able to partially adapt to these physiological challenges. Initially, low oxygen partial pressure is detected by the carotid body triggering increased breathing rate. Additionally at high altitudes the heart beats faster with a lower stroke volume. Longer term exposure, over days or weeks, results in further acclimatization to altitude. The most well known acclimatization feature is an increase in hemoglobin and red blood cell (RBC) mass in order to increase the amount of oxygen that can be carried by the blood. Increased RBC mass leads to increased demand on the heart, and other complications such as hypertension, chronic mountain sickness, and high fetal mortality.
The Tibetan highlanders often live at elevations of over 3500m above sea level. One of the hallmark evolutionary adaptation of these populations is a lack of increased hemoglobin at high elevations correlating with a variant of the HIF2A gene encoding HIF2alpha. The HIF2alpha transcription factor protein is active under low oxygen conditions and helps control RBC production. The HIF2A gene variant found in Tibetan highlanders traces its ancestry to a recently discovered extinct human relative - the Densisovans. So this particular adaptation is due to interbreeding between the Denisovans and the ancestors of modern Tibetans. EGLN1 and PPARA are also positively correlated with Tibetans low hemoglobin adaptation to hypoxia. Other unique traits of Tibetans contribute to their altitude aptitude including an increased basal breathing rate that does not go away when exposed to lower elevation, a larger lung capacity, and a higher blood nitric oxide (NO) concentration which can help blood vessel dilation and circulation. Tibetans also have experienced selection for genes involved in metabolism, DNA damage response, DNA repair, and genes for high infant birth weight.
Genetic adaptation to high altitude among Andean populations are distinct from the Tibetan adaptations. While HIF2A and EGLN1 both exhibit evidence of selection pressure in these populations the particular variants are not associated with decreased hemoglobin. In fact these populations demonstrate the same temporary increase in hemoglobin with increasing altitude that lowlanders experience. They do have an increased oxygen level in their hemoglobin and thus a more efficient oxygen blood carrying capacity. The Andeans do not have an increased breathing rate, however one Andean subpopulation also has increased NO blood concentrations. The Andeas are the least well adapted to high altitude as evidenced by the frequency of chronic mountain sickness. An examination of Andeans with chronic mountain sickness found that many individuals have maladapted gene variants of SENP1 and ANP32D.
The Amhara of Ethiopia are also unique in their adaptations to a low oxygen, high altitude environment. This population are immune to the dangers of high elevations over 2500m, and have been inhabiting these environments for much longer, yet they do not have either the decreased hemoglobin or high oxygen saturation of the Tibetans or Andeans respectively. However one study had identified several candidate genes for involvement in high-altitude adaptation in Ethiopia. Two of these play a role in the HIF1alpha pathway, suggesting some degree of convergent evolution.

An O2 mask is a pretty good altitude adaptation