Feyereisen_1995_Pest.Sci_43_233

The house fly P450 CYP6Al was cloned and sequenced. This gene was mapped to chromosome V of the house fly. Upstream of the transcription start site are sequences (barbie boxes) that may be related to the inducibility of the gene by phenobarbital. The coding sequence of CYP6Al is interrupted at the Glu364 codon by a single intron of 60 bp, as in five related CYP6 genes that are present on the same chromosome. The catalytic activity of CYP6Al was analyzed in a reconstituted system of house fly P450 reductase and CYP6Al. The cDNAs for these two components of the microsomal P450 system were expressed in Escherichia coli. CYP6Al epoxidized the cyclodiene insecticides heptachlor and aldrin at a high rate. The CYP6Al gene was shown to be constitutively overexpressed in several insecticide-resistant strains, including the multi-resistant Rutgers strain. This high constitutive expression is not caused by an amplification of the CYP6Al gene. Overexpression of the CYP6Al gene is controlled by an incompletely dominant locus on chromosome II, both in larvae and in adults. This shows that overexpression is the result of a mutation affecting a trans-acting factor that regulates CYP6Al expression on chromosome V. Metabolic resistance to insecticides (organophosphorus compounds, carbamates, juvenile hormone analogs etc.) has been mapped repeatedly to chromosome II in the house fly by genetic methods, and these results support the hypothesis of Plapp that a major resistance gene on chromosome II is a regulatory gene.