The Drosophila foraging gene: gene regulation, pleiotropy and plasticity

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Geneticists traditionally study a single well-defined function associated with a gene. However, many genes have multiple functions (pleiotropy) in different tissues and sometimes even within the same tissue. This proposal investigates how different parts of a gene support different functions, from a gene regulation perspective. We hypothesize that the foraging gene's modular structure and complexity facilitates its multiple functions. We use the fruit fly Drosophila melanogaster with its unsurpassed genetic tool kit. Our efforts are focused on the Drosophila foraging gene that encodes a signalling molecule called cGMP dependent protein kinase. The foraging gene encodes two natural allelic variants called rover and sitter. While foraging, rover flies move more and find more food than sitters. The foraging gene has many functions; in addition to foraging behaviour it modulates learning and memory, sleep, stress responses and social behaviours. In the present grant, we address how, from a molecular perspective, foraging accomplishes its pleiotropic functions in Drosophila social behaviours.  Social behaviours to be studied are: 1) Larval social foraging: Larval social foraging occurs under high-density conditions when 3rd instar larvae form groups who synchronize their downward digging into the liquified food. Under low-density rearing both sitters and rovers forage alone (solitary foraging) whereas under high density, sitters forage in groups (social foraging) while rovers (and larvae with the foraging gene genetically deleted) forage alone. 2) Adult social interaction duration: In groups, adult sitter flies have significantly longer interaction durations than rovers. Social isolation reduces the interaction duration of sitters but not rovers. Genetic analyses tie a number of adult social phenotypes to the foraging gene. The foraging gene is a complex gene comprising about 35kb of DNA. The foraging gene produces many gene products including 21 transcripts an approximately 9 protien isoforms.  The foraging gene is conserved across species and found in multiple systems, tissues and cells throughout development and adulthood of the fly. In the current proposal our objectives are to investigate 1) how the foraging gene's complex structure (multiple promoters, RNA transcripts and protein isoforms) play a modular role in Drosophila social behaviours and, 2) how social behaviours are regulated by interactions between the foraging gene and its epigenetic regulators (G9a, a histone methyl transferase gene, and the microRNA, miR-932), and how the social environment (e.g. social isolation) acts to change these patterns of regulation. This research will build a comprehensive and foundational understanding of how a complex gene affects multiple interacting phenotypes to generate normal individual differences in social behaviour.