Individual variations lead to universal and cross-species patterns of social behavior.

The duration of interaction events in a society is a fundamental measure of its collective nature and potentially reflects variability in individual behavior. Here we performed a high-throughput measurement of trophallaxis and face-to-face event durations experienced by a colony of honeybees over their entire lifetimes. The interaction time distribution is heavy-tailed, as previously reported for human face-to-face interactions. We developed a theory of pair interactions that takes into account individual variability and predicts the scaling behavior for both bee and extant human datasets. The individual variability of worker honeybees was nonzero but less than that of humans, possibly reflecting their greater genetic relatedness. Our work shows how individual differences can lead to universal patterns of behavior that transcend species and specific mechanisms for social interactions.

Honey bee virus causes context-dependent changes in host social behavior.

Anthropogenic changes create evolutionarily novel environments that present opportunities for emerging diseases, potentially changing the balance between host and pathogen. Honey bees provide essential pollination services, but intensification and globalization of honey bee management has coincided with increased pathogen pressure, primarily due to a parasitic mite/virus complex. Here, we investigated how honey bee individual and group phenotypes are altered by a virus of concern, Israeli acute paralysis virus (IAPV). Using automated and manual behavioral monitoring of IAPV-inoculated individuals, we find evidence for pathogen manipulation of worker behavior by IAPV, and reveal that this effect depends on social context; that is, within versus between colony interactions. Experimental inoculation reduced social contacts between honey bee colony members, suggesting an adaptive host social immune response to diminish transmission. Parallel analyses with double-stranded RNA (dsRNA)-immunostimulated bees revealed these behaviors are part of a generalized social immune defensive response. Conversely, inoculated bees presented to groups of bees from other colonies experienced reduced aggression compared with dsRNA-immunostimulated bees, facilitating entry into susceptible colonies. This reduction was associated with a shift in cuticular hydrocarbons, the chemical signatures used by bees to discriminate colony members from intruders. These responses were specific to IAPV infection, suggestive of pathogen manipulation of the host. Emerging bee pathogens may thus shape host phenotypes to increase transmission, a strategy especially well-suited to the unnaturally high colony densities of modern apiculture. These findings demonstrate how anthropogenic changes could affect arms races between human-managed hosts and their pathogens to potentially affect global food security.

Context-dependent influence of threat on honey bee social network dynamics and brain gene expression.

Adverse social experience affects social structure by modifying the behavior of individuals, but the relationship between an individual's behavioral state and its response to adversity is poorly understood. We leveraged naturally occurring division of labor in honey bees and studied the biological embedding of environmental threat using laboratory assays and automated behavioral tracking of whole colonies. Guard bees showed low intrinsic levels of sociability compared with foragers and nurse bees, but large increases in sociability following exposure to a threat. Threat experience also modified the expression of caregiving-related genes in a brain region called the mushroom bodies. These results demonstrate that the biological embedding of environmental experience depends on an individual's societal role and, in turn, affects its future sociability.

Division of labor in honey bees is associated with transcriptional regulatory plasticity in the brain.

Studies in evolutionary and developmental biology show that relationships between transcription factors (TFs) and their target genes can be altered to result in novel regulatory relationships that generate phenotypic plasticity. We hypothesized that context-dependent shifts in the nervous system associated with behavior may also be linked to changes in TF-target relationships over physiological time scales. We tested this hypothesis using honey bee (Apis mellifera) division of labor as a model system by performing bioinformatic analyses of previously published brain transcriptomic profiles together with new RNAi and behavioral experiments. The bioinformatic analyses identified five TFs that exhibited strong signatures of regulatory plasticity as a function of division of labor. RNAi targeting of one of these TFs (broad complex) and a related TF that did not exhibit plasticity (fushi tarazu transcription factor 1) was administered in conjunction with automated analyses of foraging behavior in the field, laboratory assays of aggression and brood care behavior, and endocrine treatments. The results showed that changes in the regulatory relationships of these TFs were associated with behavioral state, social context and endocrine state. These findings provide the first empirical evidence that TF-target relationships in the brain are altered in conjunction with behavior and social context. They also suggest that one mechanism for this plasticity involves pleiotropic TFs high up in regulatory hierarchies producing behavior-specific transcriptional responses by activating different downstream TFs to induce discrete context-dependent transcriptional cascades. These findings provide new insights into the dynamic nature of the transcriptional regulatory architecture underlying behavior in the brain.

Meta-analysis of honey bee neurogenomic response links Deformed wing virus type A to precocious behavioral maturation.

Crop pollination by the western honey bee Apis mellifera is vital to agriculture but threatened by alarmingly high levels of colony mortality, especially in Europe and North America. Colony loss is due, in part, to the high viral loads of Deformed wing virus (DWV), transmitted by the ectoparasitic mite Varroa destructor, especially throughout the overwintering period of a honey bee colony. Covert DWV infection is commonplace and has been causally linked to precocious foraging, which itself has been linked to colony loss. Taking advantage of four brain transcriptome studies that unexpectedly revealed evidence of covert DWV-A infection, we set out to explore whether this effect is due to DWV-A mimicking naturally occurring changes in brain gene expression that are associated with behavioral maturation. Consistent with this hypothesis, we found that brain gene expression profiles of DWV-A infected bees resembled those of foragers, even in individuals that were much younger than typical foragers. In addition, brain transcriptional regulatory network analysis revealed a positive association between DWV-A infection and transcription factors previously associated with honey bee foraging behavior. Surprisingly, single-cell RNA-Sequencing implicated glia, not neurons, in this effect; there are relatively few glial cells in the insect brain and they are rarely associated with behavioral plasticity. Covert DWV-A infection also has been linked to impaired learning, which together with precocious foraging can lead to increased occurrence of infected bees from one colony mistakenly entering another colony, especially under crowded modern apiary conditions. These findings provide new insights into the mechanisms by which DWV-A affects honey bee health and colony survival.

Insights into the Transcriptional Architecture of Behavioral Plasticity in the Honey Bee Apis mellifera.

Honey bee colonies exhibit an age-related division of labor, with worker bees performing discrete sets of behaviors throughout their lifespan. These behavioral states are associated with distinct brain transcriptomic states, yet little is known about the regulatory mechanisms governing them. We used CAGEscan (a variant of the Cap Analysis of Gene Expression technique) for the first time to characterize the promoter regions of differentially expressed brain genes during two behavioral states (brood care (aka "nursing") and foraging) and identified transcription factors (TFs) that may govern their expression. More than half of the differentially expressed TFs were associated with motifs enriched in the promoter regions of differentially expressed genes (DEGs), suggesting they are regulators of behavioral state. Strikingly, five TFs (nf-kb, egr, pax6, hairy, and clockwork orange) were predicted to co-regulate nearly half of the genes that were upregulated in foragers. Finally, differences in alternative TSS usage between nurses and foragers were detected upstream of 646 genes, whose functional analysis revealed enrichment for Gene Ontology terms associated with neural function and plasticity. This demonstrates for the first time that alternative TSSs are associated with stable differences in behavior, suggesting they may play a role in organizing behavioral state.