Doctoral Dissertation Research: Epigenomics of Andean High-Altitude Adaptation

Regents Of The University Of Michigan - Ann Arbor, Ann Arbor MI

Investigators

Abstract

At high altitudes, most people show a decrease in blood oxygen levels, a spike in blood pressure, and increased heart and breathing rates. However, long-term resident populations at high altitudes have unique physiological adaptations that allow them to survive and reproduce in this extreme niche. This project will examine epigenetic changes, specifically changes in DNA methylation, to understand how being born and raised at high altitude affects human biology. For many years biological anthropologists have sought to understand the heritable genetic variants that allow survival at high altitudes, and this project is significant in moving from a genetic to an epigenetic focus. Unlike high altitude gene variants that an individual either inherits or not, DNA methylation can change during an individual's lifetime because it undergoes reprogramming during early development and is therefore susceptible to the effects of the environment. Project findings will contribute to our understanding of how early development influences adaptive phenotypes to extreme environments. Identification of epigenetic changes in the hypoxia (low-oxygen) response pathway may also inform future research on the role of hypoxia in cancer etiology, cardiac ischemia, and stroke. The project will also support undergraduate and graduate training in laboratory research methods. Whole-genome and gene-specific DNA methylation signatures will be measured in one high altitude population from the Andes - the Peruvian Quechua. Study participants (n= 601) have been recruited to represent different high-altitude developmental exposures including: 1) born and raised at low altitude (n=150), 2) born at high altitude and moved to low altitude during adolescence (n = 150), 3) born and raised at high altitude (n=301). This project builds on the investigators' strong foundation of research to understand the genetic changes that contribute to high-altitude adaptation in this same population. This project allows the assessment of how genetics and epigenetics interact to create the Andean altitude-adaptive phenotype. Understanding this interaction has implications for the study of high-altitude adaptation specifically and human biological adaptation more generally.