Molecular Genetics of Aggressive Behaviour in Drosophila Melanogaster

Aggression is a key component of the normal repertoire of behaviours in a broad range of animals from insects to mammals. Although the genetic basis for aggression is widely accepted, only a few individual candidate genes have been studied. Recent studies have indicated that Drosophila melanogaster can serve as a powerful model system to study the genetics of aggression. The aim of this project was to identify genes associated with aggression by global profiling of the fly transcriptome using DNA expression microarrays. At the core of this study was a behavioural screen in which the aggression of 910 pairs of males was observed and scored. Microarray analysis revealed 350 genes that were differentially expressed between aggressive and nonaggressive flies. Several biological functions such as translation activity, immune response, ion transport, and sensory transduction were significantly over-represented. Analysis of the upstream region of these genes also suggested several shared motifs that might serve as transcription factor binding sites that drive the co-expression of these genes. One of the top differentially expressed genes was Dat, (dopamine-Nacetyltransferase), which was upregulated in aggressive flies. Dat has two isoforms generated by alternative splicing, DatA and DatB. QPCR analysis revealed that only DatB is upregulated in aggressive flies. In Datlo mutants that express only DatB, aggression is also increased, an effect that can be reverted by over-expressing the DatA transgene. Additional experiments over-expressing DatB indicate that the two isoforms effectively act in opposite ways to regulate aggression, suggesting that a balance between them is necessary for adaptive levels of aggression. Another candidate gene was CG6480, whose levels were reduced in aggressive flies. The function of this gene is unknown, but it does share a conserved motif called Fascin with its mammalian ortholog frg1. Silencing this gene by dsRNAi resulted in flies that show elevated levels of aggression.