Social environment is associated with gene regulatory variation in the rhesus macaque immune system

Jenny Tung, Luis B. Barreiro, Zachary P. Johnson, Kasper D. Hansen, Vasiliki Michopoulos, Donna Toufexis, Katelyn Michelini, Mark E. Wilson, Yoav Gilad

Research output: Contribution to journalArticlepeer-review

175 Scopus citations


Variation in the social environment is a fundamental component of many vertebrate societies. In humans and other primates, adverse social environments often translate into lasting physiological costs. The biological mechanisms associated with these effects are therefore of great interest, both for understanding the evolutionary impacts of social behavior and in the context of human health. However, large gaps remain in our understanding of the mechanisms that mediate these effects at the molecular level. Here we addressed these questions by leveraging the power of an experimental system that consisted of 10 social groups of female macaques, in which each individual's social status (i.e., dominance rank) could be experimentally controlled. Using this paradigm, we show that dominance rank results in a widespread, yet plastic, imprint on gene regulation, such that peripheral blood mononuclear cell gene expression data alone predict social status with 80% accuracy. We investigated the mechanistic basis of these effects using cell type-specific gene expression profiling and glucocorticoid resistance assays, which together contributed to rank effects on gene expression levels for 694 (70%) of the 987 rankrelated genes. We also explored the possible contribution of DNA methylation levels to these effects, and identified global associations between dominance rank and methylation profiles that suggest epigenetic flexibility in response to status-related behavioral cues. Together, these results illuminate the importance of the molecular response to social conditions, particularly in the immune system, and demonstrate a key role for gene regulation in linking the social environment to individual physiology.

Original languageEnglish (US)
Pages (from-to)6490-6495
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number17
StatePublished - Apr 24 2012


  • Differential gene expression
  • Inflammation
  • Social gradient
  • Sociogenomics

ASJC Scopus subject areas

  • General


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