scholarly journals Agonism and grooming behaviour explain social status effects on physiology and gene regulation in rhesus macaques

2022 ◽  
Vol 377 (1845) ◽  
Author(s):  
Noah D. Simons ◽  
Vasiliki Michopoulos ◽  
Mark Wilson ◽  
Luis B. Barreiro ◽  
Jenny Tung
Keyword(s):  
Gene Regulation ◽  
Social Status ◽  
Lived Experience ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Experimental Studies ◽  
Experimental Manipulation ◽  
Behavioural Interactions ◽  
Physiological Outcomes ◽  
Social Environmental

Variation in social status predicts molecular, physiological and life-history outcomes across a broad range of species, including our own. Experimental studies indicate that some of these relationships persist even when the physical environment is held constant. Here, we draw on datasets from one such study—experimental manipulation of dominance rank in captive female rhesus macaques—to investigate how social status shapes the lived experience of these animals to alter gene regulation, glucocorticoid physiology and mitochondrial DNA phenotypes. We focus specifically on dominance rank-associated dimensions of the social environment, including both competitive and affiliative interactions. Our results show that simple summaries of rank-associated behavioural interactions are often better predictors of molecular and physiological outcomes than dominance rank itself. However, while measures of immune function are best explained by agonism rates, glucocorticoid-related phenotypes tend to be more closely linked to affiliative behaviour. We conclude that dominance rank serves as a useful summary for investigating social environmental effects on downstream outcomes. Nevertheless, the behavioural interactions that define an individual's daily experiences reveal the proximate drivers of social status-related differences and are especially relevant for understanding why individuals who share the same social status sometimes appear physiologically distinct. This article is part of the theme issue ‘The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies’.

scholarly journals Agonism and grooming behavior explain social status effects on physiology and gene regulation in rhesus macaques

2021 ◽  
Author(s):  
Noah D Simons ◽  
Vasiliki Michopoulos ◽  
Mark Wilson ◽  
Luis B Barreiro ◽  
Jenny Tung
Keyword(s):  
Gene Regulation ◽  
Social Status ◽  
Lived Experience ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Experimental Studies ◽  
Experimental Manipulation ◽  
Affiliative Behavior ◽  
Behavioral Interactions ◽  
Physiological Outcomes

Variation in social status predicts molecular, physiological, and life history outcomes across a broad range of species, including our own. Experimental studies indicate that some of these relationships persist even when the physical environment is held constant. Here, we draw on data sets from one such study-experimental manipulation of dominance rank in captive female rhesus macaques-to investigate how social status shapes the lived experience of these animals to alter gene regulation, glucocorticoid physiology, and mitochondrial DNA phenotypes. We focus specifically on dominance rank-associated dimensions of the social environment, including both competitive and affiliative interactions. Our results show that simple summaries of rank-associated behavioral interactions are often better predictors of molecular and physiological outcomes than dominance rank itself. However, while measures of immune function are best explained by agonism rates, glucocorticoid-related phenotypes tend to be more closely linked to affiliative behavior. We conclude that dominance rank serves as a useful summary for investigating social environmental effects on downstream outcomes. Nevertheless, the behavioral interactions that define an individual's daily experiences reveal the proximate drivers of social status-related differences, and are especially relevant for understanding why individuals who share the same social status sometimes appear physiologically distinct.

scholarly journals Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques

2018 ◽  
Author(s):  
Noah Snyder-Mackler ◽  
Joaquín Sanz ◽  
Jordan N. Kohn ◽  
Tawni N. Voyles ◽  
Roger Pique-Regi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Social Status ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Chromatin Accessibility ◽  
High Status ◽  
Cell Gene

ABSTRACTLow social status is an important predictor of disease susceptibility and mortality risk in humans and other social mammals. These effects are thought to stem in part from dysregulation of the glucocorticoid (GC)-mediated stress response. However, the molecular mechanisms that connect low social status and GC dysregulation to downstream health outcomes remain elusive. Here, we used an in vitro glucocorticoid challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for immune cell gene regulation in female rhesus macaques, using paired control and GC-treated peripheral blood mononuclear cell samples. We show that social status not only influences immune cell gene expression, but also chromatin accessibility at hundreds of regions in the genome. Social status effects on gene expression were less pronounced following GC treatment than under control conditions. In contrast, social status effects on chromatin accessibility were stable across conditions, resulting in an attenuated relationship between social status, chromatin accessibility, and gene expression post-GC exposure. Regions that were more accessible in high status animals and regions that become more accessible following GC treatment were enriched for a highly concordant set of transcription factor binding motifs, including motifs for the glucocorticoid receptor co-factor AP-1. Together, our findings support the hypothesis that social status alters the dynamics of GC-mediated gene regulation, and identify chromatin accessibility as a mechanism involved in social stress-driven GC resistance. More broadly, they emphasize the context-dependent nature of social status effects on gene regulation and implicate epigenetic remodeling of chromatin accessibility as a contributing factor.

scholarly journals Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques

2018 ◽  
Vol 116 (4) ◽  
pp. 1219-1228 ◽  
Author(s):  
Noah Snyder-Mackler ◽  
Joaquín Sanz ◽  
Jordan N. Kohn ◽  
Tawni Voyles ◽  
Roger Pique-Regi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Social Status ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Chromatin Accessibility ◽  
High Status ◽  
Cell Gene

Low social status is an important predictor of disease susceptibility and mortality risk in humans and other social mammals. These effects are thought to stem in part from dysregulation of the glucocorticoid (GC)-mediated stress response. However, the molecular mechanisms that connect low social status and GC dysregulation to downstream health outcomes remain elusive. Here, we used an in vitro GC challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for immune cell gene regulation in female rhesus macaques, using paired control and GC-treated peripheral blood mononuclear cell samples. We show that social status not only influences immune cell gene expression but also chromatin accessibility at hundreds of regions in the genome. Social status effects on gene expression were less pronounced following GC treatment than under control conditions. In contrast, social status effects on chromatin accessibility were stable across conditions, resulting in an attenuated relationship between social status, chromatin accessibility, and gene expression after GC exposure. Regions that were more accessible in high-status animals and regions that become more accessible following GC treatment were enriched for a highly concordant set of transcription factor binding motifs, including motifs for the GC receptor cofactor AP-1. Together, our findings support the hypothesis that social status alters the dynamics of GC-mediated gene regulation and identify chromatin accessibility as a mechanism involved in social stress-driven GC resistance. More broadly, they emphasize the context-dependent nature of social status effects on gene regulation and implicate epigenetic remodeling of chromatin accessibility as a contributing factor.

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

2018 ◽  
Author(s):  
Amanda J. Lea ◽  
Mercy Y. Akinyi ◽  
Ruth Nyakundi ◽  
Peter Mareri ◽  
Fred Nyundo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Social Status ◽  
Rhesus Macaques ◽  
Dominance Rank ◽  
Immune Gene ◽  
High Status ◽  
Social Hierarchies ◽  
The Relationship ◽  
High Social Status

ABSTRACTIn humans and other hierarchical species, social status is tightly linked to variation in health and fitness-related traits. Experimental manipulations of social status in female rhesus macaques suggest that this relationship is partially explained by status effects on immune gene regulation. However, social hierarchies are established and maintained in different ways across species: while some are based on kin-directed nepotism, others emerge from direct physical competition. We investigated how this variation influences the relationship between social status and immune gene regulation in wild baboons, where hierarchies in males are based on fighting ability but female hierarchies are nepotistic. We measured rank-related variation in gene expression levels in adult baboons of both sexes at baseline and in response to ex vivo stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We identified >2000 rank- associated genes in males, an order of magnitude more than in females. In males, high status predicted increased expression of genes involved in innate immunity and preferential activation of the NFkB-mediated pro-inflammatory pathway, a pattern previously associated with low status in female rhesus macaques. Using Mendelian randomization, we reconcile these observations by demonstrating that high status-associated gene expression patterns are precursors, not consequences, of high social status in males, in support of the idea that physiological condition determines who attains high rank. Together, our work provides the first test of the relationship between social status and immune gene regulation in wild primates. It also emphasizes the importance of social context in shaping the relationship between social status and immune function.SIGNIFICANCESocial status predicts fitness outcomes in social animals, motivating efforts to understand its physiological causes and consequences. We investigated the relationship between social status and immune gene expression in wild baboons, where female status is determined by kinship but male status is determined by fighting ability. We uncover pervasive status-gene expression associations in males, but not females. High status males exhibit high levels of pro-inflammatory gene expression, in contrast to previous findings in hierarchies that are not competitively determined. Using Mendelian randomization, we show that this status-associated variation precedes dominance rank attainment: males who compete successfully for high status are already immunologically distinct. The nature of social hierarchies thus fundamentally shapes the relationship between social status and immune function.

scholarly journals REVERSE TRANSLATION OF HUMAN BIO-AGING MEASURES TO CYNOMOLGUS MONKEYS TO TEST ASSOCIATIONS WITH DOMINANCE RANK

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S349-S349
Author(s):  
Noah Snyder-Mackler ◽  
Carol Shively ◽  
Tom Register ◽  
Daniel W Belsky
Keyword(s):  
Social Status ◽  
Dominance Rank ◽  
Blood Chemistry ◽  
Experimental Manipulation ◽  
Biological Aging ◽  
Primate Model ◽  
Cynomolgus Monkeys ◽  
Health Decline ◽  
Using Data ◽  
Human Primate

Abstract Social status is a powerful correlate of aging-related health decline. Observational data in humans suggest that disadvantaged social status may be associated with accelerated biological aging. But establishing causality in this relationship poses challenges; experimental manipulation of human social status is not possible. In contrast, social status can be experimentally manipulated non-human primates (e.g. Snyder-Mackler 2016 Science). We conducted analysis to reverse-translate blood-chemistry of biological aging to cynomolgus monkeys using data from several hundred animals in the Wake Primate Center breeding colony. We are applying these measures in an independent sample of monkeys with ascertained dominance rank to test replication in the non-human primate model of the human social gradient in biological aging. Parallel analysis of DNA methylation-based measures of biological aging are ongoing and should be available to present by Fall 2019. Results will inform potential to use this non-human primate model to study social determinants of biological aging.

scholarly journals Distinct gene regulatory signatures of dominance rank and social bond strength in wild baboons

2022 ◽  
Vol 377 (1845) ◽  
Author(s):  
Jordan A. Anderson ◽  
Amanda J. Lea ◽  
Tawni N. Voyles ◽  
Mercy Y. Akinyi ◽  
Ruth Nyakundi ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Bond Strength ◽  
Social Environment ◽  
Dominance Rank ◽  
Social Bond ◽  
Immune Gene ◽  
The Social ◽  
Social Environmental ◽  
Change Response ◽  
Wild Baboons

The social environment is a major determinant of morbidity, mortality and Darwinian fitness in social animals. Recent studies have begun to uncover the molecular processes associated with these relationships, but the degree to which they vary across different dimensions of the social environment remains unclear. Here, we draw on a long-term field study of wild baboons to compare the signatures of affiliative and competitive aspects of the social environment in white blood cell gene regulation, under both immune-stimulated and non-stimulated conditions. We find that the effects of dominance rank on gene expression are directionally opposite in males versus females, such that high-ranking males resemble low-ranking females, and vice versa. Among females, rank and social bond strength are both reflected in the activity of cellular metabolism and proliferation genes. However, while we observe pronounced rank-related differences in baseline immune gene activity, only bond strength predicts the fold-change response to immune (lipopolysaccharide) stimulation. Together, our results indicate that the directionality and magnitude of social effects on gene regulation depend on the aspect of the social environment under study. This heterogeneity may help explain why social environmental effects on health and longevity can also vary between measures. This article is part of the theme issue ‘The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies’.

scholarly journals Decoupling social status and status certainty effects on health in macaques: a network approach

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2394 ◽  
Author(s):  
Jessica J. Vandeleest ◽  
Brianne A. Beisner ◽  
Darcy L. Hannibal ◽  
Amy C. Nathman ◽  
John P. Capitanio ◽  
...  
Keyword(s):  
Physical Health ◽  
Social Status ◽  
Social Life ◽  
Rhesus Macaques ◽  
Social Systems ◽  
Dominance Rank ◽  
Primate Model ◽  
Necrosis Factor Alpha ◽  
General Physical ◽  
The Impact

BackgroundAlthough a wealth of literature points to the importance of social factors on health, a detailed understanding of the complex interplay between social and biological systems is lacking. Social status is one aspect of social life that is made up of multiple structural (humans: income, education; animals: mating system, dominance rank) and relational components (perceived social status, dominance interactions). In a nonhuman primate model we use novel network techniques to decouple two components of social status, dominance rank (a commonly used measure of social status in animal models) and dominance certainty (the relative certainty vs. ambiguity of an individual’s status), allowing for a more complex examination of how social status impacts health.MethodsBehavioral observations were conducted on three outdoor captive groups of rhesus macaques (N = 252 subjects). Subjects’ general physical health (diarrhea) was assessed twice weekly, and blood was drawn once to assess biomarkers of inflammation (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP)).ResultsDominance rank alone did not fully account for the complex way that social status exerted its effect on health. Instead, dominance certainty modified the impact of rank on biomarkers of inflammation. Specifically, high-ranked animals with more ambiguous status relationships had higher levels of inflammation than low-ranked animals, whereas little effect of rank was seen for animals with more certain status relationships. The impact of status on physical health was more straightforward: individuals with more ambiguous status relationships had more frequent diarrhea; there was marginal evidence that high-ranked animals had less frequent diarrhea.DiscussionSocial status has a complex and multi-faceted impact on individual health. Our work suggests an important role of uncertainty in one’s social status in status-health research. This work also suggests that in order to fully explore the mechanisms for how social life influences health, more complex metrics of social systems and their dynamics are needed.

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

2018 ◽  
Vol 115 (52) ◽  
pp. E12163-E12171 ◽  
Author(s):  
Amanda J. Lea ◽  
Mercy Y. Akinyi ◽  
Ruth Nyakundi ◽  
Peter Mareri ◽  
Fred Nyundo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Social Status ◽  
Rhesus Macaques ◽  
Immune Gene ◽  
High Status ◽  
Female Rhesus ◽  
The Relationship ◽  
High Social Status ◽  
Female Rhesus Macaques

In humans and other hierarchical species, social status is tightly linked to variation in health and fitness-related traits. Experimental manipulations of social status in female rhesus macaques suggest that this relationship is partially explained by status effects on immune gene regulation. However, social hierarchies are established and maintained in different ways across species: While some are based on kin-directed nepotism, others emerge from direct physical competition. We investigated how this variation influences the relationship between social status and immune gene regulation in wild baboons, where hierarchies in males are based on fighting ability but female hierarchies are nepotistic. We measured rank-related variation in gene expression levels in adult baboons of both sexes at baseline and in response to ex vivo stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We identified >2,000 rank-associated genes in males, an order of magnitude more than in females. In males, high status predicted increased expression of genes involved in innate immunity and preferential activation of the NF-κB–mediated proinflammatory pathway, a pattern previously associated with low status in female rhesus macaques. Using Mendelian randomization, we reconcile these observations by demonstrating that high status-associated gene expression patterns are precursors, not consequences, of high social status in males, in support of the idea that physiological condition determines who attains high rank. Together, our work provides a test of the relationship between social status and immune gene regulation in wild primates. It also emphasizes the importance of social context in shaping the relationship between social status and immune function.

scholarly journals Distinct gene regulatory signatures of dominance rank and social bond strength in wild baboons

2021 ◽  
Author(s):  
Jordan Anderson ◽  
Amanda J Lea ◽  
Tawni Voyles ◽  
Mercy Akinyi ◽  
Ruth Nyakundi ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Bond Strength ◽  
Social Environment ◽  
Dominance Rank ◽  
Social Bond ◽  
Immune Gene ◽  
The Social ◽  
Social Environmental ◽  
Change Response ◽  
Wild Baboons

The social environment is a major determinant of morbidity, mortality, and Darwinian fitness in social animals. Recent studies have begun to uncover the molecular processes associated with these relationships, but the degree to which they vary across different dimensions of the social environment remains unclear. Here, we draw on a long-term field study of wild baboons to compare the signatures of affiliative and competitive aspects of the social environment in white blood cell gene regulation, under both immune stimulated and non-stimulated conditions. We find that the effects of dominance rank on gene expression are directionally opposite in males versus females, such that high-ranking males resemble low-ranking females, and vice-versa. Among females, rank and social bond strength are both reflected in the activity of cellular metabolism and proliferation genes. However, pronounced rank-related differences in baseline immune gene activity are near-absent for social bond strength, while only bond strength predicts the fold-change response to immune (lipopolysaccharide) stimulation. Together, our results indicate that the directionality and magnitude of social effects on gene regulation depend on the aspect of the social environment under study. This heterogeneity may help explain why social environmental effects on health and longevity can also vary between measures.

scholarly journals Rhesus macaques form preferences for brand logos through sex and social status based advertising

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0193055 ◽  
Author(s):  
M. Yavuz Acikalin ◽  
Karli K. Watson ◽  
Gavan J. Fitzsimons ◽  
Michael L. Platt
Keyword(s):  
Social Status ◽  
Rhesus Macaques ◽  
Brand Logos
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