Accelerated Evolution of Context-Dependent Gene Expression in Primate Immune Cells

Abstract

Regulatory variation is widely recognized as a driver of evolution within and between species, including in the primate lineage. Evidence for potentially adaptive regulatory evolution in primates comes from both sequence-based tests for selection and cross-species comparisons of gene expression. However, comparative studies of gene expression have tended to focus on baseline cellular states, despite growing evidence that context-dependent gene regulation is important. Here, we investigate the evolution of gene expression in lymphoblastoid cell lines (LCLs) from 6 primate lineages (humans, chimpanzees, bonobos, western gorillas, Sumatran orangutans, and rhesus macaques) using data from both control and 5 perturbed cellular conditions (n=22-25 individuals per condition). Analyzing baseline expression data, we find that genes involved in immunity often exhibit lineage-specific transcriptional shifts, and that these genes occur near regions with lineage-specific sequence acceleration and lineage-specific epigenomic states. However, the subset of genes that respond to in vitro perturbations have evolved at significantly higher rates than environmentally-insensitive genes, a finding we replicate in an independent four-species dataset of primary white blood cells (n=26). Together, our findings support the argument that focusing on baseline states alone provides a biased view of gene regulatory evolution, and suggest that studying gene regulation in dynamic contexts can enrich our understanding of primate evolution.