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Variation in the social environment is a fundamental component of many vertebrate societies and has broad effects on gene regulation, particularly in the immune system.
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.
Many species, including humans, have social hierarchies that affect mating and other behaviors that are important for survival. A growing body of evidence suggests that the stress of a low social ranking can also influence mental and physical health in a variety of ways. These include suppressed immune function and elevated risk for cardiovascular problems like hypertension, heart disease and stroke. Yet little is known on a molecular level about how social stress translates into physiological
changes.
In the new study, researchers investigated whether social status affects gene regulation. The work, funded by several NIH components, was led by University of Chicago researchers Dr. Jenny Tung (now at Duke University) and Dr. Yoav Gilad. It was described in the April 9, 2012, advance online edition of the Proceedings of the National Academy of
Sciences.
Here researchers 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, researchers 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. They 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 rank-related
genes.
The social status of 7 macaques changed during the study, giving the scientists an opportunity to confirm that gene expression changes with social rank. They found that gene expression levels could correctly determine the social rank of 6 out of the 7
females.
Scientists 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.
This study provides insight into the links researchers have long observed between social stress and physiology. More work will be needed to fully understand the mechanisms by which social status affects gene expression and health
outcomes.
Source
Social environment is associated with gene regulatory variation in the rhesus macaque immune system
Authors
Jenny Tung, Luis B. Barreiro, Zachary P. Johnson, Kasper D. Hansen, Vasiliki Michopoulos,
Donna Toufexis, Katelyn Michelini, Mark E. Wilson, and Yoav Gilad.
(MDN)
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