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 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 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 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 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’.

Why Do High-Status People Have Larger Social Networks? Belief in Status-Quality Coupling as a Driver of Network-Broadening Behavior and Social Network Size

2020 ◽  
Author(s):  
Jiyin Cao ◽  
Edward Bishop Smith
Keyword(s):  
Social Networks ◽  
Social Network ◽  
Social Status ◽  
Positive Association ◽  
Network Size ◽  
High Status ◽  
Discussion Section ◽  
Social Network Size ◽  
Tightly Coupled ◽  
The Relationship

Previous research has demonstrated that the size and reach of people’s social networks tend to be positively related to their social status. Although several explanations help to account for this relationship—for example, higher-status people may be part of multiple social circles and therefore have more social contacts with whom to affiliate—we present a novel argument involving people’s beliefs about the relationship between status and quality, what we call status-quality coupling. Across seven separate studies, we demonstrate that the positive association between social status and network-broadening behavior (as well as social network size) is contingent on the extent to which people believe that status is a reliable indicator of quality. Across each of our studies, high- and low-status people who viewed status and quality as tightly coupled differed in their network-broadening behaviors, as well as in the size of their reported social networks. The effect was largely driven by the perceived self-value and perceived receptivity of the networking target. Such differences were significantly weaker or nonexistent among equivalently high- and low-status people who viewed status as an unreliable indicator of quality. Because the majority of participants—both high- and low-status—exhibited beliefs in status-quality coupling, we conclude that such a belief marks an important and previously unaccounted-for driver of the relationship between status, network-broadening behaviors, and social networks. Implications for research on social capital, advice seeking, and inequality are highlighted in the discussion section.

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

2019 ◽  
Vol 117 (38) ◽  
pp. 23317-23322 ◽  
Author(s):  
Joaquín Sanz ◽  
Paul L. Maurizio ◽  
Noah Snyder-Mackler ◽  
Noah D. Simons ◽  
Tawni Voyles ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Status ◽  
Social History ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Expression Patterns ◽  
Social Experience ◽  
Type I ◽  
Gene Expression Response ◽  
Expression Of Genes

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB–dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB– and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history—in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

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 Diet modulates the relationship between immune gene expression and functional immune responses

2019 ◽  
Vol 109 ◽  
pp. 128-141 ◽  
Author(s):  
Sheena C. Cotter ◽  
Catherine E. Reavey ◽  
Yamini Tummala ◽  
Joanna L. Randall ◽  
Robert Holdbrook ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Immune Gene ◽  
Immune Gene Expression ◽  
The Relationship
Sign in / Sign up

Export Citation Format

Share Document