Genome scan for cis-regulatory DNA motifs associated with social behavior in honey bees

Honey bees (Apis mellifera) undergo an age-related, socially regulated transition from working in the hive to foraging, which is associated with changes in the expression of thousands of genes in the brain. To begin to study the cis-regulatory code underlying this massive social regulation of gene expression, we used the newly sequenced honey bee genome to scan the promoter regions of eight sets of behaviorally related genes differentially expressed in the brain in the context of division of labor among worker bees, for 41 cis-regulatory motifs previously characterized in Drosophila melanogaster. Binding sites for the transcription factors Hairy, GAGA, Adf1, Cf1, Snail, and Dri, known to function in nervous system development, olfactory learning, or hormone binding in Drosophila, were significantly associated with one or more gene sets. The presence of some binding sites also predicted expression patterns for as many as 71% of the genes in some gene sets. These results suggest that there is a robust relationship between cis and social regulation of brain gene expression, especially considering that we studied <15% of all known transcription factors. These results also suggest that transcriptional networks involved in the regulation of development in Drosophila are used to regulate behavioral development in adult honey bees. However, differences in gene regulation between these two processes are suggested by the finding that the promoter regions for the behaviorally related bee genes differed in both motif occurrence and G/C content relative to their Drosophila orthologs.