Dominance rank-associated gene expression is widespread, sex-specific, and a precursor to high social status in wild male baboons

Abstract

SignificanceSocial status can predict health, reproduction, and survival in social animals. To understand why, we investigated social status and immune gene expression in wild baboons, where kinship determines status in females but fighting ability determines status in males. We identified a much stronger relationship between status and gene expression in males than females. Further, inflammation-related genes were more active in high-status than low-status males; the opposite effect has been reported in status hierarchies that are not determined by fighting ability. Our results suggest that males who compete successfully for high status are already immunologically distinct. They therefore emphasize that how social hierarchies are formed shapes their relationship to immune function and health.

The costs of competition: high social status males experience accelerated epigenetic aging in wild baboons

“…In support of this interpretation, a model that includes rank-for-age as an additional covariate recapitulates the significant effect of ordinal male rank (p=0.045), but finds no effect of rank-for-age (p=0.819; Table S4). In contrast, we observed no evidence for rank effects on Δ age in females, consistent with overall sex differences in patterns of aging in primates and other mammals [15] and marked sex differences in the effects of rank on other molecular phenotypes in the Amboseli baboons specifically [11, 28].…”

“…Elevated or chronic inflammation is thought to be one of the hallmarks of aging, and, in human populations, is one of the strongest predictors of mortality risk [29–31]. Consistent with these observations, CpG sites in the epigenetic clock that increase in DNA methylation with age (N = 459 sites) are enriched in or near genes that are up-regulated in the Amboseli baboons in response to the bacterial endotoxin lipopolysaccharide (LPS), which is a strong driver of inflammation (Figure S3; Fisher’s exact test: log 2 (odds ratio) = 1.88, p = 0.001; gene expression data from [28]). In contrast, clock sites that decrease in DNA methylation with age (N = 134) are significantly enriched in or near genes that are down-regulated after LPS exposure (Fisher’s exact test: log 2 (OR) = 3.28, p = 0.002).…”

“…Previous work has shown that high-ranking male baboons, but not high-ranking female baboons, up-regulate gene expression in inflammation-related and immune response pathways [28]. Elevated or chronic inflammation is thought to be one of the hallmarks of aging, and, in human populations, is one of the strongest predictors of mortality risk [29–31].…”

Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

“…Convergent evidence from humans, wild animal populations, and experimental animal models indicates that social interactions are reflected in the regulation and activity of the immune system (6,7,11,(26)(27)(28)48). Our findings join those of others to suggest that social adversity is particularly relevant to the inflammatory response, one of the first lines of defense in the innate immune system (49).…”

“…This relationship is thought to arise in part through changes in gene regulation, which mediate the genomic response to physiological signals of social stress (e.g., glucocorticoids, adrenaline, noradrenaline; (6,7)). Gene expression signatures of social status and social adversity have now been reported in multiple studies, encompassing clinical and population-based samples in humans, and studies of both experimental and natural populations in other social animals (6,(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)) (see also (20)(21)(22)(23)(24)(25) for evidence in social insects and other social vertebrates). Because this work has concentrated most extensively on peripheral white blood cells, it provides a direct window into how social experiences are reflected in the regulation of the immune system (26)(27)(28).…”