Genetics of human origin and evolution: high-altitude adaptations

Abstract

High altitude, defined as elevations lying above 2,500 m sea level, challenges human survival and reproduction. This environment provides a natural experimental design wherein specific populations, Andeans, Ethiopians, and Tibetans, have lived in a chronic hypoxia state for millennia. These human groups have overcome the low ambient oxygen tension of high elevation via unique physiologic and genetic adaptations. Genomic studies have identified several genes that underlie high-altitude adaptive phenotypes, many of which are central components of the Hypoxia Inducible Factor (HIF) pathway. Further study of mechanisms governing the adaptive changes responsible for high-altitude adaptation will contribute to our understanding of the molecular basis of evolutionary change and assist in the functional annotation of the human genome.

Deletion of the fih gene encoding an inhibitor of hypoxia-inducible factors increases hypoxia tolerance in zebrafish

“…Over evolutionary time, aerobic organisms have developed sophisticated cellular mechanisms that sense and respond to O 2 gradients, as well as physiological systems that adapt to changes in these gradients (1)(2)(3)(4)(5)(6). As consistent oxygen supply affects evolution, studies of hypoxia adaptation (chronic hypoxia) are common (5,7,8). However, organisms often encounter acute hypoxic conditions in addition to chronic hypoxia (5,(7)(8)(9), yet organis-mal mechanisms of adaptation to chronic hypoxia (i.e.…”

Hypoxia and Placental Development

“…There are other human populations indigenous to the Andes, Ethiopia, and Tibet, which represent altitude‐adaptive natives (Bigham, ). These individuals have acquired uteroplacental adaptations that enhance pregnancy performance, fetal growth, and facilitate offspring survival (Hochachka and Rupert, ; Beall et al, ; Zamudio et al, ).…”

“…These individuals have acquired uteroplacental adaptations that enhance pregnancy performance, fetal growth, and facilitate offspring survival (Hochachka and Rupert, ; Beall et al, ; Zamudio et al, ). Most interestingly, these populations possess polymorphisms in genes that are directly linked to hypoxia‐dependent adaptations (Bigham, ). Among the targeted loci are genes encoding key components of the HIF signaling pathway, including HIF1A , EPAS1 , EGLN1 , etc., which have also been linked to placentation (see above).…”

Centennial perspective on human adaptability

“…Since the mid‐1970s, extensive comparative research among other high altitude groups (e.g., Tibetans, Ethiopians) has shown remarkable diversity in adaptive patterns across populations (Beall, ; Bigham, ; Moore et al, ; Moore, Neirmeyer, & Zamudio, ). To date, the differences between Andean (Quechua, Aymara) and Himalayan (Tibetan) populations have been most widely studied and are best understood (see Beall, ; Moore et al, ).…”