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:Venoms have convergently evolved in all major animal lineages and are ideal candidates to unravel the underlying genomic processes of convergent trait evolution. However, few animal groups have been studied in detail, and large-scale comparative genomic analyses to address toxin gene evolution are rare. Hyper-diverse hymenopterans are the most speciose group of venomous animals, but the origin of their toxin genes have been largely overlooked. We combined proteo-transcriptomics with comparative genomics compiling an up-to-date list of core bee venom proteins to investigate the origin of 11 venom genes in 30 hymenopteran genomes including two new stingless bees.
Project description:Venoms have convergently evolved in all major animal lineages and are ideal candidates to unravel the underlying genomic processes of convergent trait evolution. However, few animal groups have been studied in detail, and large-scale comparative genomic analyses to address toxin gene evolution are rare. Hyper-diverse hymenopterans are the most speciose group of venomous animals, but the origin of their toxin genes have been largely overlooked. We combined proteo-transcriptomics with comparative genomics compiling an up-to-date list of core bee venom proteins to investigate the origin of 11 venom genes in 30 hymenopteran genomes including two new stingless bees.
Project description:We studied behavioral, brain transcriptomic and epigenetic responses of honey bees to social challenge. Bees were exposed to two intruders at different intervals. The initial exposure caused two behavioral effects at the individual level: an increase in the intensity of aggression toward a second intruder at 30 and 60 minutes, and an increased probability of responding aggressively toward a second intruder that persisted for two hours. The shorter-lived response was associated with one pattern of gene expression in the mushroom bodies, highlighted by genes related to cytoskeleton remodeling. The longer-lived response was associated with a different pattern; highlighted by genes related to hormones, stress response and transcription factors. Histone profiling revealed few changes in chromatin accessibility in response to social challenge; most differentially expressed genes were “ready” to be activated. These results demonstrate how biological embedding of a social challenge involves changes in the neurogenomic state to influence future behavior.
Project description:E.O. Wilson proposed in Sociobiology that similarities between human and animal societies reflect common mechanistic and evolutionary roots. When introduced in 1975 this controversial hypothesis was beyond science’s ability to test and remains unproven. We used genomic analyses to determine whether superficial behavioral similarities in humans and the highly social honey bee reflect common molecular mechanisms. Here we report that gene expression signatures for individual bees unresponsive to various salient social stimuli are significantly enriched for autism spectrum disorder-related genes. These signatures occur in the mushroom bodies, a high-level integration center of the insect brain. Further, our finding of enrichment was unique to autism spectrum disorders; brain gene expression signatures from other honey bee behaviors do not show this enrichment, nor do data sets from other human behavioral and health conditions. These results demonstrate deep conservation for genes associated with a human social pathology and individual differences in insect social behavior, thus providing an example of how comparative genomics can be used to test sociobiological theory.
Project description:BACKGROUND: Social insects, such as honey bees, use molecular, physiological and behavioral responses to combat pathogens and parasites. The honey bee genome contains all of the canonical insect immune response pathways, and several studies have demonstrated that pathogens can activate expression of immune effectors. Honey bees also use behavioral responses, termed social immunity, to collectively defend their hives from pathogens and parasites. These responses include hygienic behavior (where workers remove diseased brood) and allo-grooming (where workers remove ectoparasites from nestmates). We have previously demonstrated that immunostimulation causes changes in the cuticular hydrocarbon profiles of workers, which results in altered worker-worker social interactions. Thus, cuticular hydrocarbons may enable workers to identify sick nestmates, and adjust their behavior in response. Here, we test the specificity of behavioral, chemical and genomic responses to immunostimulation by challenging workers with a panel of different immune stimulants (saline, Sephadex beads and Gram-negative bacteria E. coli). RESULTS: While only bacteria-injected bees elicited altered behavioral responses from healthy nestmates compared to controls, all treatments resulted in significant changes in cuticular hydrocarbon profiles. Immunostimulation caused significant changes in expression of hundreds of genes, the majority of which have not been identified as members of the canonical immune response pathways. Furthermore, several new candidate genes that may play a role in cuticular hydrocarbon biosynthesis were identified. Finally, we identified common genes regulated by pathogen challenge in honey bees and other insects, suggesting that immune responses are conserved at the molecular level. CONCLUSIONS: These studies suggest that honey bee genomic responses to immunostimulation are substantially broader than expected, and may mediate the behavioral changes associated with social immunity by orchestrating changes in chemical signaling.
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.