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

doi:10.1093/molbev/mst089

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

Computational and RNA Biology

112 Citations (Scopus)

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.

Original language	English
Journal	Molecular Biology and Evolution
Volume	30
Issue number	8
Pages (from-to)	1877-1888
Number of pages	12
ISSN	0737-4038
DOIs	https://doi.org/10.1093/molbev/mst089
Publication status	Published - 2013

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http://mbe.oxfordjournals.org/content/30/8/1877.abstract

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Huerta-Sánchez, E., DeGiorgio, M., Pagani, L., Tarekegn, A., Ekong, R., Antao, T., Cardona, A., Montgomery, H. E., Cavalleri, G. L., Robbins, P. A., Weale, M. E., Bradman, N., Bekele, E., Kivisild, T., Tyler-Smith, C., & Nielsen, R. (2013). Genetic signatures reveal high-altitude adaptation in a set of Ethiopian populations. Molecular Biology and Evolution, 30(8), 1877-1888. https://doi.org/10.1093/molbev/mst089

Huerta-Sánchez, E, DeGiorgio, M, Pagani, L, Tarekegn, A, Ekong, R, Antao, T, Cardona, A, Montgomery, HE, Cavalleri, GL, Robbins, PA, Weale, ME, Bradman, N, Bekele, E, Kivisild, T, Tyler-Smith, C & Nielsen, R 2013, 'Genetic signatures reveal high-altitude adaptation in a set of Ethiopian populations', Molecular Biology and Evolution, vol. 30, no. 8, pp. 1877-1888. https://doi.org/10.1093/molbev/mst089

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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.",

author = "Emilia Huerta-S{\'a}nchez and Michael DeGiorgio and Luca Pagani and Ayele Tarekegn and Rosemary Ekong and Tiago Antao and Alexia Cardona and Montgomery, {Hugh E.} and Cavalleri, {Gianpiero L.} and Robbins, {Peter A.} and Weale, {Michael E.} and Neil Bradman and Endashaw Bekele and Toomas Kivisild and Chris Tyler-Smith and Rasmus Nielsen",

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AU - Huerta-Sánchez, Emilia

AU - DeGiorgio, Michael

AU - Pagani, Luca

AU - Tarekegn, Ayele

AU - Ekong, Rosemary

AU - Antao, Tiago

AU - Cardona, Alexia

AU - Montgomery, Hugh E.

AU - Cavalleri, Gianpiero L.

AU - Robbins, Peter A.

AU - Weale, Michael E.

AU - Bradman, Neil

AU - Bekele, Endashaw

AU - Kivisild, Toomas

AU - Tyler-Smith, Chris

AU - Nielsen, Rasmus

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1093/molbev/mst089

DO - 10.1093/molbev/mst089

M3 - Journal article

C2 - 23666210

SN - 0737-4038

VL - 30

SP - 1877

EP - 1888

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

IS - 8

ER -

Genetic signatures reveal high-altitude adaptation in a set of Ethiopian populations

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