Genome-wide association mapping of natural variation in odour-guided behaviour in Drosophila

A defining goal in the field of behavioural genetics is to identify the key genes or genetic networks that shape behaviour. A corollary to this goal is the goal of identifying genetic variants that are responsible for variation in the behaviour. These goals are achieved by measuring behavioural responses to controlled stimuli, in the present case the responses of Drosophila melanogaster to olfactory stimuli. We used a high-throughput behavioural assay system to test a panel of 157 Drosophila inbred lines derived from a natural population for both temporal and spatial dynamics of odour-guided behaviour. We observed significant variation in response to the odourant 2,3-butanedione, a volatile compound present in fermenting fruit. The recent whole genome sequencing of these inbred lines allowed us to then perform genome-wide association analyses in order to identify genetic polymorphisms underlying variation in responses. These analyses revealed numerous single nucleotide polymorphisms associated with variation in responses. Among the candidate genes identified were both novel and previously identified olfaction-related genes. Further, gene network analyses suggest that genes influencing variation in odour-guided behaviour are enriched for functions involving neural processing and that these genes form a pleiotropic interaction network. We examined several of these candidate genes that were highly connected in the protein- and genetic interaction networks using RNA interference. Our results showed that subtle changes influencing nervous system function can result in marked differences in behaviour.