Doctoral Dissertation Research: The genetic basis of epigenetic variation and environmental response in primates

New York University, New York NY

Investigators

Abstract

Genetic changes which influence the regulation of how and when genes are expressed are a prominent source of heritable differences between individuals. Individuals differ in their degree of epigenetic marks across the genome, which are chemical changes that do not impact the DNA sequence but that alter which genes are turned on or off. This doctoral dissertation research uses a non-human primate population to investigate the genetic differences responsible for epigenetic differences between individuals, and to study how an individual’s social or ecological environment may modify the relationship between genotype and gene regulation. This research aids our understanding of complex genotype-phenotype relationships in primates and identifies the genes where genetic differences may contribute to differential risk or susceptibility following exposure to adversity. This has potential implications for human populations facing similar experiences, including psychosocial stressors and natural disasters. This project trains a female graduate student in STEM and supports high school and undergraduate research mentoring initiatives for individuals from groups that are underrepresented in science. Gene regulatory change is an important mechanism of primate evolution and regulatory differences within populations correlate with fitness-relevant traits. Despite this, the genetic variants responsible for these differences are relatively unknown. This research tests the hypothesis that sequence variation predicts individual differences in a well-known epigenetic mark, DNA methylation, in functional regions of the genome, and that gene-environment interactions (GxE) are prominent contributors to phenotypic differences at the molecular level. The project generates whole genome and methylation data from the same individuals to identify genetic variants associated with methylation differences in the population, and explores the epigenetic changes associated with individual social status and hurricane exposure, to identify context-dependent genetic effects on methylation at environmentally sensitive sites (GxE). The research reveals genes whose expression is sensitive to environmental and genetic changes, and the sources of individual differences in physiological response to the same environmental stressor. Finally, the project comprehensively catalogues the factors that best explain differences in DNA methylation at each site in the genome to determine the relative contribution of genetic, environmental, and GxE effects to gene regulatory variation. Project outcomes shed light on the proximate mechanisms driving transcriptional differences across individuals and environments and generating phenotypic variation on which selection can act. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.