Deep evolutionary conservation of autism-related genes

Abstract

E. O. Wilson proposed inSociobiology 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. 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 highlevel integration center of the insect brain. Furthermore, 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 datasets 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.autism | evolution | honey bee | social behavior | transcriptomics

Cross‐species systems analysis of evolutionary toolkits of neurogenomic response to social challenge

“…Ascertainment of the conserved components of a behavioral toolkit permit translational work in the future, such as the use of “bottom‐up” approaches for identifying similarities in behaviors across widely diverged species through similarities in functional genomic profiling . This approach already shows promise; recent work reported similarities in the gene sets related to social responsiveness in humans and honey bees . To that point, although we discussed the role and neurobiological relevance of some of the abovementioned systems in detail in our previous work—we described hormone receptors in sticklebacks, developmental TFs in mice, dendritic architecture in honey bees and GPCRs in all three species—the present work identifies core systems relating to social behavior.…”

Honey bee neurogenomic responses to affiliative and agonistic social interactions

“…The discovery of genes expressed in the MB that respond in the same direction to both an affiliative (this study) and agonistic stimulus provides further evidence that this brain region is involved in processing social information . The similarity of the transcriptional responses is significant for two reasons.…”

“…R 2 and P ‐value were obtained from Pearson correlation analysis. (C) Venn diagram of the shared responding genes and gene list related to social responsiveness in honey bees . *** Significant overlap (hypergeometric test p < 0.0001) between the gene lists (universe—10 317 genes)…”

“…We hypothesized that this shared set of DEGs captured the common component of the response to the two stimuli: the social nature of the signal. To explore this idea, we compared the shared GLM gene list (136 genes), which captures the gene expression profile of bees responding to social stimuli, with another previously published DEG list of 605 genes related to responsiveness to the same two stimuli . There was a significant overlap, but this only involved 18 genes across the two lists (hypergeometric test; p = 0.001, Figure C).…”

“…The shared genes were enriched for nuclear receptors like Hr38 (homolog of mammalian Nr4a ) and chaperones, which have a role in nuclear receptor signal transduction . The shared genes also overlapped with genes related to social responsiveness in humans, suggesting that at least some, but not all, of these genes are involved in social signal transduction, the common character of both stimuli.…”