Neuromolecular responses to social challenge: common mechanisms across mouse, stickleback fish, and honey bee

Abstract

Certain complex phenotypes appear repeatedly across diverse species due to processes of evolutionary conservation and convergence. In some contexts like developmental body patterning, there is increased appreciation that common molecular mechanisms underlie common phenotypes; these molecular mechanisms include highly conserved genes and networks that may be modified by lineage-specific mutations. However, the existence of deeply conserved mechanisms for social behaviors has not yet been demonstrated. We used a comparative genomics approach to determine whether shared neuromolecular mechanisms could underlie behavioral response to territory intrusion across species spanning a broad phylogenetic range: house mouse (Mus musculus), stickleback fish (Gasterosteus aculeatus), and honey bee (Apis mellifera). Territory intrusion modulated similar brain functional processes in each species, including those associated with hormone-mediated signal transduction and neurodevelopment. Changes in chromosome organization and energy metabolism appear to be core, conserved processes involved in the response to territory intrusion. We also found that several homologous transcription factors that are typically associated with neural development were modulated across all three species, suggesting that shared neuronal effects may involve transcriptional cascades of evolutionarily conserved genes. Furthermore, immunohistochemical analyses of a subset of these transcription factors in mouse again implicated modulation of energy metabolism in the behavioral response. These results provide support for conserved genetic "toolkits" that are used in independent evolutions of the response to social challenge in diverse taxa.

Keywords: NF-κB signaling; aggression; brain metabolism; genetic hotspot.

Fig. 1.

Major biological processes (Top) and molecular functions (Bottom) regulated in response to territory intrusion for each species as revealed by Gene Ontology analysis of genes differentially expressed in the brain in response to social challenge. Clustering analyses of single-species GSEA results (adjusted P value < 0.05) are shown. Shading of circles indicates relative significance of the GO term (darker is more significant). Circle size corresponds to the number of genes annotated to the term in the reference database. See Datasets S1–S3 for full lists.

Fig. 2.

Clustering analyses for the homologous triplet GSEA (adjusted P value < 0.05). Triplets were groups of orthologous or paralogous genes as identified by OrthoDB. (Left) Clustering analyses include all significant terms. (Right) Analyses include only terms unique to the homologous triplet GSEA (not identified in any of the single-species analyses). See Dataset S5 for full list.

Fig. 3.

Toolkit TF proteins, identified as responsive to social challenge in all three species, localized in mouse brain with immunohistochemistry. Sagittal sections from resident animals were treated with antibodies to EMX1, FOXG1, and NR5A1. Antibodies, stained in red, detected very similar clustered populations of neurons in the ventromedial hypothalamus (VMH); NR5A1 was additionally detected in scattered neurons within the arcuate hypothalamic nucleus (AHN).