Genetic Signatures Reveal High-Altitude Adaptation in a Set of Ethiopian Populations

Emilia Huerta-Sánchez, Michael DeGiorgio, Luca Pagani, Ayele Tarekegn, Rosemary Ekong, Tiago Antao, Alexia Cardona, Hugh E. Montgomery, Gianpiero L. Cavalleri, Peter A. Robbins, Michael E. Weale, Neil Bradman, Endashaw Bekele, Toomas Kivisild, Chris Tyler-Smith, Rasmus Nielsen

Research output: Contribution to journalArticlepeer-review

148 Scopus citations


The Tibetan and Andean Plateaus and Ethiopian highlands are the largest regions to have long-term high-altitude residents. Such populations are exposed to lower barometric pressures and hence atmospheric partial pressures of oxygen. Such "hypobaric hypoxia" may limit physical functional capacity, reproductive health, and even survival. As such, selection of genetic variants advantageous to hypoxic adaptation is likely to have occurred. Identifying signatures of such selection is likely to help understanding of hypoxic adaptive processes. Here, we seek evidence of such positive selection using five Ethiopian populations, three of which are from high-altitude areas in Ethiopia. As these populations may have been recipients of Eurasian gene flow, we correct for this admixture. Using single-nucleotide polymorphism genotype data from multiple populations, we find the strongest signal of selection in BHLHE41 (also known as DEC2 or SHARP1). Remarkably, a major role of this gene is regulation of the same hypoxia response pathway on which selection has most strikingly been observed in both Tibetan and Andean populations. Because it is also an important player in the circadian rhythm pathway, BHLHE41 might also provide insights into the mechanisms underlying the recognized impacts of hypoxia on the circadian clock. These results support the view that Ethiopian, Andean, and Tibetan populations living at high altitude have adapted to hypoxia differently, with convergent evolution affecting different genes from the same pathway.

Original languageEnglish (US)
Pages (from-to)1877-1888
Number of pages12
JournalMolecular biology and evolution
Issue number8
StatePublished - 2013

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics


Dive into the research topics of 'Genetic Signatures Reveal High-Altitude Adaptation in a Set of Ethiopian Populations'. Together they form a unique fingerprint.

Cite this