Social Landscape and Genetic Variation Shape Gene Regulation in a Natural Primate Population

Abstract

Gene expression, defined as the quantity of mRNA transcribed, reflects the functional deployment of the genome and provides an interesting link between environment and evolution. Gene expression responds plastically to social and ecological conditions, connecting external experience to physiological processes under the skin. At the same time, gene expression is influenced by inherited genetic differences that have evolved under natural selection. To fully connect ecology, evolution, and genomics, it is important to understand both environmental and genetic sources of gene expression variation, yet these two factors are rarely studied together in wild populations. My dissertation fills this gap by exploring how the social environment and genetic variation together affect gene regulation in immune cells of wild baboons from Kenya’s Amboseli ecosystem, a population that has been monitored longitudinally for over five decades.In Chapter 1, I deconstruct the multidimensional social landscape of male baboons and describe its regulatory signatures in peripheral immune gene expression. Using 13 social behavioral measures, I identify two behaviorally coherent clusters representing the competitive and affiliative dimensions of social relationships, each linked with distinct effects in both constitutive gene expression and the transcriptional response to immune stimulation. I further identify neutrophil proportion as a key mediator of the association between social behavior and gene expression, deepening our understanding of this link from what genes are affected to how the social environment becomes biologically embedded, in part, through compositional changes in circulating immune cells. In Chapter 2, I develop and optimize a genotype imputation pipeline for low-coverage whole-genome sequencing data, utilizing external genetic resources to obtain genome-wide, high-quality, low-missingness genotypes for the Amboseli population. This work expands the available genomic resources, unlocks opportunities for downstream genetic analyses, and provides general guidance for conducting genotype imputation in non-model systems. In Chapter 3, I characterize the genetic architecture of both constitutive gene expression and the regulatory response to immune stimulation. I further investigate how the evolution of this regulatory genetic architecture relates to ancestry-associated gene expression divergence, and test whether cis-regulatory variants have developed true effect size heterogeneity. I find that differences in allele frequency of regulatory variants can explain the majority of the observed ancestry effects on gene expression, indicating that the cis-regulatory genetic architecture has remained largely conserved over 1.4 million years of lineage divergence. Taken together, my work establishes clear connections between the social environment, genetic variation, and gene regulation in a wild primate population, revealing both transient regulatory responses to social experience and stable genetic architectures shaped by long-term evolutionary processes. These contributions help bridge key gaps in our understanding of how ecological and genetic forces jointly shape immune gene expression and their evolution in natural primate populations.