Andean and Tibetan patterns of adaptation to high altitude

Bigham, Abigail W.; Wilson, Megan J.; Julian, Colleen G.; Kiyamu, Melisa; Vargas, Enrique; León‐Velarde, Fabiola; Rivera-Chira, María; Rodriquez, Carmelo; Browne, Vaughn A.; Parra, Esteban J.; Brutsaert, Tom D.; Moore, Lorna G.; Shriver, Mark D.

doi:10.1002/ajhb.22358

Cited by 113 publications

(102 citation statements)

References 54 publications

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“…Of note, the candidate genes identified for Andeans and Tibetans are largely distinct from one another, but PHD2 has emerged as a candidate for both populations. Further analysis reveals that among Tibetans, variants in this gene are associated with hemoglobin concentration, while among Andeans, they are not (Simonson et al 2010;Bigham et al 2013;Xiang et al 2013). In the Tibetan population, two nonsynonymous coding variants located in exon1-rs12097901 (C127S) and rs186996510 (D4E)-have been observed at high frequency.…”

Section: Tibetan Adaptation To High Altitude and Genetic Analysesmentioning

confidence: 99%

Human high-altitude adaptation: forward genetics meets the HIF pathway

2014

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Humans have adapted to the chronic hypoxia of high altitude in several locations, and recent genome-wide studies have indicated a genetic basis. In some populations, genetic signatures have been identified in the hypoxia-inducible factor (HIF) pathway, which orchestrates the transcriptional response to hypoxia. In Tibetans, they have been found in the HIF2A (EPAS1) gene, which encodes for HIF-2α, and the prolyl hydroxylase domain protein 2 (PHD2, also known as EGLN1) gene, which encodes for one of its key regulators, PHD2. High-altitude adaptation may be due to multiple genes that act in concert with one another. Unraveling their mechanism of action can offer new therapeutic approaches toward treating common human diseases characterized by chronic hypoxia.

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Section: Tibetan Adaptation To High Altitude and Genetic Analysesmentioning

confidence: 99%

Human high-altitude adaptation: forward genetics meets the HIF pathway

2014

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“…Numerous genetic associations have been reported in small series of patients with HAPH, including gene polymorphisms in ACE (encoding angiotensin-converting enzyme), 61 EPAS1 (encoding HIF-2a), 62 GUCY1A3 (encoding soluble guanylate cyclase), 63 and EGLN1 (encoding prolyl hydroxylase 2). 64 In contrast, the much lower PAP of native Tibetans is associated with different polymorphisms of EPAS1 and EGLN1 than those with HAPH described above.…”

Section: High-altitude Pulmonary Hypertensionmentioning

confidence: 67%

High-Altitude Pulmonary Vascular Diseases

Neupane

Swenson

2017

Advances in Pulmonary Hypertension

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More than 140 million people permanently reside in high-altitude regions of Asia, South America, North America, and Africa. Another 40 million people travel to these places annually for occupational and recreational reasons, and are thus exposed to the low ambient partial pressure of oxygen. This review will focus on the pulmonary circulatory responses to acute and chronic high-altitude hypoxia, and the various expressions of maladaptation and disease arising from acute pulmonary vasoconstriction and subsequent remodeling of the vasculature when the hypoxic exposure continues. These unique conditions include high-altitude pulmonary edema, high-altitude pulmonary hypertension, subacute mountain sickness, and chronic mountain sickness.

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“…It is thus tempting to speculate that through its evolution in this region, M. musculus has gained, and retained, specific traits of resitance to low oxygen levels. Similar processes occured in human Andean natives over a time frame of 10,000 to 15,000 years (Bigham et al, 2013), or roughly 500-1000 generations of HA residents, that can be achieved in a much shorther time frame in mice.…”

Section: Hif-1α Expression Is Correlated With Respiratory and Metabolmentioning

confidence: 96%

HIF1α and physiological responses to hypoxia are correlated in mice but not in rats

Jochmans-Lemoine

Shahare

Soliz

et al. 2016

Journal of Experimental Biology

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We previously reported that rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600 m), display divergent physiological responses to high altitude, including improved respiratory and metabolic control in mice. In the present study, we asked whether these traits would also be present in response to hypoxia at sea level. To answer this question, we exposed rats (Sprague Dawley) and mice (FVB) to normoxia (21% O 2 ) or hypoxia (15 and 12% O 2 ) for 6 h and measured ventilation and metabolic rate (whole-body plethysmography), and expression of the transcription factor HIF-1α (ELISA and mass spectrometry) and other proteins whose expression are regulated by hypoxia (glucose transporter 1, pyruvate dehydrogenase kinase 1 and angiopoietin 2; mass spectrometry) in the brainstem. In response to hypoxia, compared with rats, mice had higher minute ventilation, lower metabolic rate and higher expression of HIF-1α in the brainstem. In mice, the expression level of HIF-1α was positively correlated with ventilation and negatively correlated with metabolic rate. In rats, the concentration of brainstem cytosolic protein decreased by 38% at 12% O 2 , while expression of the glucose transporter 1 increased. We conclude that mice and rats raised at sea level have divergent physiological and molecular responses to hypoxia, supporting the hypothesis that mice have innate traits that favor adaptation to altitude.

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Andean and Tibetan patterns of adaptation to high altitude

Abstract: These results contribute to our understanding of the unique set of adaptations developed in different highland groups to the hypoxia of high altitude. Overall, the results provide key insights into the patterns of genetic adaptation to high altitude in Andean and Tibetan populations.

Cited by 113 publications

References 54 publications

Human high-altitude adaptation: forward genetics meets the HIF pathway

Human high-altitude adaptation: forward genetics meets the HIF pathway

High-Altitude Pulmonary Vascular Diseases

HIF1α and physiological responses to hypoxia are correlated in mice but not in rats

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