DISSERTATION RESEARCH: Early social experience and epigenetic mediation of adult phenotypes

Michigan State University, East Lansing MI

Investigators

Abstract

Rodent models, studies of captive primates, and data from human populations indicate that early life experiences have long-lasting effects on health, and that early life experiences and longevity often vary with socioeconomic status. This study utilizes existing data and archived biospecimens from a long-term field study of a gregarious mammal with a social structure permitting comparisons among status classes to assess effects of the early social environment on temperament and fitness. Effects of the early environment to be assessed include quality of maternal care, peer interactions and social status. Available data and specimens permit exploration of relationships among the early social environment, mechanisms of gene expression, circulating stress hormones, individual temperament, and longevity. The methods employed include high-throughput next-generation DNA sequencing techniques, bioinformatics and advanced statistical methods. Broader impacts of this work include a deeper understanding of social and molecular determinants of adverse stress phenotypes. Ultimately, characterization of the early life social factors that shape adult stress phenotypes in free-living, gregarious mammals will facilitate generalization of the research findings to other social species, including our own. In addition to supporting the scientific work above, this project will facilitate a workshop series on research methods and data analysis designed specifically for members of the African Graduate Student Association at Michigan State University. Social experiences early in life have lasting effects on adult temperament and stress phenotype, often through epigenetic modification of genes, and thus patterns of gene expression, that coordinate the hypothalamic-pituitary-adrenal axis. Using data from the MSU Mara Hyena Project, a 28-year study of free-living, gregarious hyenas in Kenya, this proposal will investigate how social factors relate to adverse stress phenotypes, and elucidate the extent to which this relationship is mediated by DNA methylation. Funding from this project will support two research goals. First, this proposal will use Reduced Representation Bisulfite Sequencing (RRBS) to identify differentially methylated regions (DMRs) of the hyena genome that are associated with high vs. low stress phenotypes based on assessment of adult hyena temperament and stress hormones, as well as differences in early social experiences including maternal rank, maternal care, and interactions with clan mates. DMRs that are predictive of the adult stress phenotypes will be identified using Mixed Model Association for Count data via data Augmentation. The second goal is to use mediation analysis to assess whether the identified socially-induced, stress-related epigenetic pathways mediate the effect of early experience on longevity. Findings from this work will improve mechanistic understanding of how social factors affect behavioral and physiological stress phenotypes in an important new animal model. Because a proximate epigenetic mechanism (DNA methylation) is assessed in relation to an ultimate consequence (fitness), this work represents a large step forward in terms of understanding the role of epigenetics in evolution - a concept that has been largely unexplored.