Genetics of human origin and evolution: high-altitude adaptations

Abstract

High altitude, defined as elevations lying above 2500m 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.

Figure 1. HIF pathway candidate genes for human adaptation to high altitude

The three geographic regions where humans have adapted to high altitude are highlighted in blue and include the Andean Altiplano, Semien Plateau, and the Tibetan Plateau. HIF pathway candidate genes for each population are listed in each of the population boxes. Genes listed in black are unique to the particular population, blue are shared between all three, green are shared between Tibetan and Andean, red are shared between Andean and Ethiopian, and purple are shared between Tibetan and Ethiopian.