Project description:DNA methylation (DNAm) influences when and where genes are expressed or repressed during growth and development. Recently, patterns of DNAm at conserved genomic sites have been discovered that predict chronological age in all mammals. Deviations from these ‘epigenetic clocks’ have been used to identify factors that alter the aging process. In this study, we profile DNAm with a custom microarray for over 330 wild Phyllostomus hastatus, a highly polygynous bat in which unrelated females form long-lasting associations and larger males compete aggressively to control mating access to female groups. DNAm age estimates reveal that females can live more than 1.5 times as long as males. After fitting linear models for age, sex and their interaction we find that DNAm changes 1.4 times faster in males than females at thousands of sites. Therefore, even though age of either sex can be predicted by a common set of sites, the methylome of males is more dynamic than that of females. Sites associated with differences in the rate of change between males and females are sensitive to androgens and enriched on the X chromosome. Those that gain methylation with age in both sexes are associated with active and repressive chromatin states in blood and are enriched in promoters of genes involved in regulation of metabolic processes. In contrast, few sites differ in DNAm rate between males of different reproductive status, though subordinate males exhibit faster DNAm change than dominant males. Thus, males have accelerated physiological processes in comparison to females that likely increase mating success but reduce survival.
Project description:Social status is one of the strongest predictors of disease risk and mortality in humans, and often influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined a functional genomics approach with sequential social status manipulations in rhesus macaques to investigate how social status alters immune function. We demonstrate causal, but largely plastic, effects of social status on immune cell proportions, cell type-specific gene expression levels, and the gene expression and cytokine response to infection. Further, we identify specific transcription factor signaling pathways that explain these differences, particularly status-associated polarization of the TLR4 signaling pathway towards pro-inflammatory versus anti-viral responses. Our findings provide an unprecedented level of insight into the direct biological effects of social inequality on immune function, thus contributing to an improved understanding of social gradients in health and the evolution of social hierarchies. For social status, please refer to table S1 in the manuscript.
Project description:Social status is one of the strongest predictors of disease risk and mortality in humans, and often influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined a functional genomics approach with sequential social status manipulations in rhesus macaques to investigate how social status alters immune function. We demonstrate causal, but largely plastic, effects of social status on immune cell proportions, cell type-specific gene expression levels, and the gene expression and cytokine response to infection. Further, we identify specific transcription factor signaling pathways that explain these differences, particularly status-associated polarization of the TLR4 signaling pathway towards pro-inflammatory versus anti-viral responses. Our findings provide an unprecedented level of insight into the direct biological effects of social inequality on immune function, thus contributing to an improved understanding of social gradients in health and the evolution of social hierarchies. For social status, please refer to table S1 in the manuscript.
Project description:Social status is one of the strongest predictors of disease risk and mortality in humans, and often influences Darwinian fitness in social mammals more generally. To understand the biological basis of these effects, we combined a functional genomics approach with sequential social status manipulations in rhesus macaques to investigate how social status alters immune function. We demonstrate causal, but largely plastic, effects of social status on immune cell proportions, cell type-specific gene expression levels, and the gene expression and cytokine response to infection. Further, we identify specific transcription factor signaling pathways that explain these differences, particularly status-associated polarization of the TLR4 signaling pathway towards pro-inflammatory versus anti-viral responses. Our findings provide an unprecedented level of insight into the direct biological effects of social inequality on immune function, thus contributing to an improved understanding of social gradients in health and the evolution of social hierarchies. For social status, please refer to table S1 in the manuscript.
Project description:Social experiences are an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a pro-inflammatory 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 pro-inflammatory pathways and lower expression of genes involved in the antiviral response and type I interferon (IFN) signaling (see Snyder-Mackler et al. Science, 2016 doi:10.1126/science.aah3580 and GSE83304). Here we show that, counter to predictions, 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 not only linked 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. 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.
Project description:Rearing conditions may elicit noticeable plastic responses in life-history traits of living organisms. For instance, diet composition has proven to influence prominent traits such as body size, fecundity, and lifespan. In contrast, the social environment may influence the survival rate at immature stages, food consumption, and fat storage. Nevertheless, the physiological mechanisms underlying such responses are largely unknown. In this study, we investigated changes in the proteome of the house cricket Acheta domesticus subjected to diets of different nutritional composition (i.e., protein to carbohydrates ratio) and two distinct social environments (i.e., solitary or in groups). We measured the relative abundances of 685 proteins identified in whole-body cricket samples using high-performance liquid chromatography coupled to tandem mass spectrometry. Differential expression of proteins induced by diet composition and social environment in female and male A. domesticus was assessed in a data-independent proteomics approach. Additionally, we performed a functional analysis of the differentially expressed proteins using comprehensive databases (KEGG and GO). We found that sex alone explained a significant portion (40.87%) of the relative protein abundance variation. Males had a higher representation of proteins involved in metabolic pathways and locomotion. In contrast, females exhibited a higher abundance of proteins related to genetic processes regulation and nutrient catabolism. Moreover, diet composition and social environment induced sex-specific changes in a smaller set of proteins with particular roles. Females had their protein profile affected by diet composition and social environment. The involved proteins were mainly related to several protein synthesis stages, carbohydrate metabolism, and muscle development. In contrast, males were only affected by diet composition, overexpressing proteins related to hormone production, carbohydrate metabolism, and apparently depositing excess protein in the cuticle when fed with a protein-rich diet. It was evident that diet had a more substantial influence on the proteome of the cricket A. domesticus than the social environment, showing that diet composition may exert profound physiological changes in insects in a sex-specific manner.
Project description:In humans, mutations in the transcription factor encoding gene, FOXP2, are associated with language and Autism Spectrum (ASD) Disorders, the latter characterized by deficits in social interactions. However, little is known regarding the function of Foxp2 in male or female social behavior. Our previous studies in mice revealed high expression of Foxp2 within the medial subnucleus of the amygdala (MeA), a limbic brain region highly implicated in innate social behaviors such as mating, aggression, and parental care. Here, using a comprehensive panel of behavioral tests in male and female Foxp2+/- heterozygous mice, we investigated the role Foxp2 plays in MeA-linked innate social behaviors. We reveal significant deficits in olfactory processing, social interaction, mating, aggressive and parental behaviors. Interestingly, some of these deficits displayed in a sex-specific manner. To examine the consequences of Foxp2 loss of function specifically in the MeA, we conducted a proteomic analysis of microdissected MeA tissue and found sex differences in a host of proteins implicated in neuronal communication, connectivity and dopamine signaling. Consistent with this, we discovered that MeA Foxp2-lineage cells were responsive to dopamine with differences between males and females. Thus, our findings reveal a central and sex-specific role for Foxp2 in social behavior and MeA function.
Project description:Sperm competition theory predicts that males should tailor ejaculates according to their social status. Here we test this in a model vertebrate, the house mouse (Mus musculus domesticus), combining experimental data with a quantitative proteomics analysis of seminal fluid composition. Our analyses reveal that both sperm production and the relative production of proteins found in seminal fluid differ according to social dominance. Notably, whereas dominant males produce and ejaculate more sperm, subordinate males produce greater relative amounts of key proteins used in the formation of copulatory plugs. These findings have important implications for understanding the dynamics and outcome of sperm competition.
Project description:We report gene expression patterns for the flatworm Macrostomum lignano in four different social envirionments expected to influence allocation to the male and female sex functions