Genome-Wide Epigenetic Signatures of Adaptive Developmental Plasticity in the Andes

Author:

Childebayeva Ainash123,Goodrich Jaclyn M2,Leon-Velarde Fabiola4,Rivera-Chira Maria4,Kiyamu Melisa4,Brutsaert Tom D5,Dolinoy Dana C26,Bigham Abigail W7

Affiliation:

1. Department of Anthropology, University of Michigan

2. Department of Environmental Health Sciences, School of Public Health, University of Michigan

3. Department of Archaeogenetics, Max Planck Institute for the Study of Human History, Jena, Germany

4. Departamento de Ciencias Biológicas y Fisiológicas, Universidad Peruana Cayetano Heredia, Lima, Peru

5. Department of Exercise Science, Syracuse University

6. Department of Nutritional Sciences, School of Public Health, University of Michigan

7. Department of Anthropology, University of California, Los Angeles

Abstract

Abstract High-altitude adaptation is a classic example of natural selection operating on the human genome. Physiological and genetic adaptations have been documented in populations with a history of living at high altitude. However, the role of epigenetic gene regulation, including DNA methylation, in high-altitude adaptation is not well understood. We performed an epigenome-wide DNA methylation association study based on whole blood from 113 Peruvian Quechua with differential lifetime exposures to high altitude (>2,500) and recruited based on a migrant study design. We identified two significant differentially methylated positions (DMPs) and 62 differentially methylated regions (DMRs) associated with high-altitude developmental and lifelong exposure statuses. DMPs and DMRs were found in genes associated with hypoxia-inducible factor pathway, red blood cell production, blood pressure, and others. DMPs and DMRs associated with fractional exhaled nitric oxide also were identified. We found a significant association between EPAS1 methylation and EPAS1 SNP genotypes, suggesting that local genetic variation influences patterns of methylation. Our findings demonstrate that DNA methylation is associated with early developmental and lifelong high-altitude exposures among Peruvian Quechua as well as altitude-adaptive phenotypes. Together these findings suggest that epigenetic mechanisms might be involved in adaptive developmental plasticity to high altitude. Moreover, we show that local genetic variation is associated with DNA methylation levels, suggesting that methylation associated SNPs could be a potential avenue for research on genetic adaptation to hypoxia in Andeans.

Publisher

Oxford University Press (OUP)

Subject

Genetics,Ecology, Evolution, Behavior and Systematics

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