Rush hour traffic can change an otherwise rational individual into a violent menace. Dierick et al. suggest that differential expression of a small number of genes can strongly influence aggressive behavior in a recent article in Nature Genetics.
The authors selectively bred Drosophila for aggressive behavior. They evaluated flies in a large Plexiglas cage with food-filled 'territories' and selected flies that won several territorial challenges as founders for an aggressive line of flies. In a separate population, they discarded the aggressive flies and randomly selected founders for a neutral line of flies. In each successive generation, they bred selected males to randomly selected virgin females from the same line. 'Escalated' fighting, in which flies rise onto their hind legs to box or wrestle, accounts for less than five percent of all Drosophila fights. After seven generations, the authors only selected flies participating in escalations to breed aggressive flies.
The authors developed a multi-chambered cage for high-throughput analysis of non-territorial aggression. After 11 generations of repeated selection, more aggressive flies than neutral flies engaged in escalated fighting. Aggressive flies showed shorter latencies to fight, spent a greater percentage of time fighting and had more intense fighting bouts that included tossing or holding an opponent than did neutral flies. After another 10 generations of selection (generation 21), even neutral flies that fought did so less vigorously and for a shorter period of time than did aggressive flies. Aggressive flies almost always dominated neutral flies in mixed populations. Most non-aggressive behaviors were similar in aggressive and neutral flies.
The authors identified approximately 80 genes differentially expressed in aggressive and neutral fly heads using stringent microarray experiments. In the mouse, serotonin is involved in aggression, but none of the genes differentially expressed in the aggressive and neutral flies related to serotonin production or signaling. Expression differences were generally small, with only four genes differing more than twofold between groups. Thirty-eight genes differed by more than twenty-five percent. The authors examined six of these genes using quantitative PCR and confirmed the expression differences for five, including genes encoding a voltage-gated potassium channel (CG3397) which was upregulated, and phosphatidyl serine synthase (CG4825), a cytochrome P450 enzyme (Cyp6a20) and an odorant-binding protein (Obp56a), which were all downregulated in aggressive relative to neutral flies. Cytochrome P450s are membrane-associated enzymes that metabolize hormones and drugs. Of the five genes validated by quantitative PCR, P-element disruption of only Cyp6a20 altered aggressive behavior.
In Drosophila, cytochrome P450 enzymes localize to olfactory regions and may be important in pheromone signaling. Odorant-binding proteins are also involved in pheromone recognition. The authors observed that in addition to reported aggressive behaviors, flies dragged their abdomens to mark their territories. They speculated that aggressive flies might be insensitive to pheromones important in territory marking and may therefore be more willing to battle for control of marked territories.