Epigenetics and behavioural plasticity: drosophila euchromatin histone metiltransferase and foraging

A thesis submitted in fulfillment of the requirements for the degree of Masters in Molecular Genetics and Biomedicine

The foraging gene in D. melanogaster underlies a natural polymorphism with two variants called rover and sitter. These variants differ in a suite of phenotypes which are plastic when exposed to varying environmental parameters. Although the phenotypic differences between rovers and sitters are evident, the underlying molecular mechanisms involved are not completely understood. Recently, a histone methyltransferase (EHMT) was found to methylate histones at the foraging promoter region, suggesting a possible interaction of these two genes. This work provides strong evidence that EHMT significantly affects several phenotypic traits linked to the foraging gene. EHMT is needed for the plastic response to food-deprivation seen in larval feeding behaviour, evident as food-deprived larvae lacking EHMT show the same behaviour as fed larva, while larva with functional EHMT significantly reduce their path-lengths when food-deprived. Furthermore, the loss of functional EHMT affects sitter but not rover adult foraging behaviour in food-deprived flies, suggesting an epigenetic interaction between EHMT and the foraging alleles. EHMT mutants also have higher fat storage levels and survive longer during starvation. And finally, EHMT mutants and revertants do not differ significantly in overall foraging RNA expression in fed and food-deprived feeding regimes, but show substantial differences in the foraging protein isoforms expressed. Taken together, this thesis provides proof that EHMT epigenetically regulates traits influenced by the foraging gene and that this regulation is linked to environmental cues. Considering that both foraging and EHMT have homologues in many species and have been associated to a series of human diseases, the results herein are also interesting from a human perspective.