title: Genetic signatures reveal high-altitude adaptation in a set of ethiopian populations.
abstract: 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.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, CA, USA. emiliahsc@berkeley.edu
authors.forename: Emilia
authors.initials: E
authors.lastname: Huerta-Sánchez
authors.forename: Michael
authors.initials: M
authors.lastname: Degiorgio
authors.forename: Luca
authors.initials: L
authors.lastname: Pagani
authors.forename: Ayele
authors.initials: A
authors.lastname: Tarekegn
authors.forename: Rosemary
authors.initials: R
authors.lastname: Ekong
authors.forename: Tiago
authors.initials: T
authors.lastname: Antao
authors.forename: Alexia
authors.initials: A
authors.lastname: Cardona
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Montgomery
authors.forename: Gianpiero L
authors.initials: GL
authors.lastname: Cavalleri
authors.forename: Peter A
authors.initials: PA
authors.lastname: Robbins
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weale
authors.forename: Neil
authors.initials: N
authors.lastname: Bradman
authors.forename: Endashaw
authors.initials: E
authors.lastname: Bekele
authors.forename: Toomas
authors.initials: T
authors.lastname: Kivisild
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
mesh_terms: D000064:Acclimatization / Q000235:genetics*; D000531:Altitude; D005075:Biological Evolution; D005002:Ethiopia; D053263:Gene Regulatory Networks; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D000860:Hypoxia / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D059467:Transcriptome
keywords: adaptation to high altitude; natural selection