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Jenny Tung Shows Impact of Rank on Gene Expression

The expression of nearly 1,000 genes changed dramatically with changes in the social rank of female rhesus macaque monkeys, according to a study led by Jenny Tung while a post-doctoral researcher at the University of Chicago.

Tung’s study is the first to demonstrate a clear link between social status and genetic regulation in primates on a genome-wide scale. It also shows an unexpectedly strong and plastic link between social environment and biology.

Tung conducted her study using rhesus macaques housed in groups of five at the Yerkes National Primate Research Center in Atlanta. Each group self-organized into a social hierarchy defined through dominance during competition for food, water and grooming partners. Tung’s group was able to study how changing social rank produces biological changes because dominance among captive monkeys is determined by the order in which the individuals are introduced into the group.

“In the wild females would not ordinarily leave the social group they were born into,” said Tung. “They inherit their social rank from their mothers. But in this unnatural situation, order of introduction determines rank — the newcomer is generally lower status.”

The researchers weren’t surprised to confirm that high-ranking rhesus macaque females showed a significant difference in the expression of genes involved in the immune response and other functions than their low-ranking group mates. Previous research had established that social rank influences the stress response as well as the brain, and immune system. But gene chip technology allowed Tung and her group to measure the expression of over 6,000 different genes and could quickly detect changes precipitated by changes in social rank. This technique allowed them to make the surprising discovery that gene expression changed within weeks of an improvement in rank. No prior study had suggested that social forces can influence genetic regulation so quickly.

“Demonstrating these very plastic and temporal changes was novel and quite interesting,” said Yoav Gilad, associate professor of human genetics at the University of Chicago Biological Sciences and senior author of the study.

Measurements of the gene expression of 49 different female monkeys of varying rank revealed significant changes in the expression of 987 genes, including 112 genes associated with immune system function. The results were consistent with earlier data showing that monkeys of low rank who suffered chronic stress ended up with compromised immune function. It was also consistent with human studies linking low socioeconomic status and high social stress to elevated disease risk.

The expression changes were so clear that Tung’s group could accurately predict a monkey’s social rank from their gene expression profile alone. That predictive power enabled the group so measure whether an impromptu change in social rank would be reflected in the gene expression of the monkeys in the group.

Tung’s group noticed that simply by removing a couple of monkeys from a cage and introducing new ones, they could improve the social ranks of a few of the remaining monkeys. That gave the researchers an opportunity to test for changes in the gene expression signatures by analyzing blood samples taken before and after the move. They found that socially-induced gene expression changes are not stable, but change in response to changes in social environment.

“There’s a spooky side to this kind of research, in that an individual’s social rank is partially determining health status,” said Tung. “But there’s also a hopeful side. For the seven females that changed ranks, their gene status changed with them. They’re not stuck in place, and I think that says something more broadly about the capacity for change.”

The researchers also uncovered the mechanism by which social status could influence gene expression. The glucocorticoid stress hormone system and the cell composition of blood samples changed with social changes, leading to the marked changes in gene expression.

Tung’s study also showed for the first time that social rank influenced the affected genes’ DNA methylation, a mechanism that can temporarily turn genes on and off. Genes that changed expression with changes in social rank were more likely to be methylated, suggesting that this mechanism also plays a role in the social influence on genetic regulation.

“That’s a novel mechanism that people haven’t considered in primates,” Gilad said. “I know that some have been resistant to the possibility of methylation changes on this timescale, but this is a demonstration that this mechanism also matters.”

While the study’s findings can’t be generalized to humans without further testing, Gilad noted that it was encouraging to think that people may be bring about beneficial changes to their health by making changes to stressful social environments.

Funding for the research was provided by the National Institutes of Health. The study was published in the Proceedings of the National Academy of Sciences.

Jenny Tung is currently an assistant professor of evolutionary anthropology at Duke University. She had conducted the study described above while a postdoctoral student at the University of Chicago. She graduated from Duke with a B.S. in biology in 2003. She completed her PhD work in biology between 2003 and 2010. She conducted postdoctoral research in the department of human genetics at the University of Chicago from 2010 until 2011.

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