Diversity and transcriptional regulation of cytochrome P450s in Drosophila

The central role of insect cytochrome P450 enzymes in resistance to insecticides and plant toxins is well established. Cactophilic Drosophila of the Sonoran Desert possess P450s that metabolize (in vitro) the toxic isoquinoline alkaloids in columnar cacti that serve as the organisms' feeding/breeding substrates. The extensive background on the natural history of the Cactus-Microorganism-Drosophila Model System provides an excellent context in which to investigate the evolution of insect-host plant interactions.;Northern analyses of mRNA isolated from larvae exposed to cactus allelochemicals or phenobarbital has demonstrated the responsiveness of individual genes to xenobiotics. Data from Northern analyses suggest that cactophilic Drosophila have independently recruited different P450s for the detoxication of cactus allelochemicals. This is based on the observation that patterns of mRNA induction by alkaloids, triterpene glycosides and phenobarbital differ for putative orthologs. Future studies involving germ-line transformation of D. melanogaster which is not tolerant of cactus allelochemicals will help to definitively demonstrate the functional roles of individual P450s. Molecular phylogenies based on a full-length gene sequences will also provide further insight into the evolution of P450-mediated biochemical resistance.;The mechanisms underlying the evolution of P450-mediated resistance remain to be fully elucidated. The DNA turnover events that gave rise to the genetic and functional diversity of the P450 superfamily make it difficult to identify orthologous sequences in other than closely related species. This, in turn, complicates the construction molecular phylogenies. To establish a framework within which to address salient questions of P450 evolution, a 3...