CONSERVED PROMOTER ELEMENTS IN THE CYP6B GENE FAMILY SUGGEST COMMON ANCESTRY FOR CYTOCHROME-P450 MONOOXYGENASES MEDIATING FURANOCOUMARIN DETOXIFICATION

Despite the fact that Papilio glaucus and Papilio polyxenes share no s ingle hostplant species, both species feed to varying extents on hostp lants that contain furanocoumarins. P. glaucus contains two nearly ide ntical genes, CYP6B4v2 and CYP6B5v1, and P. polyxenes contains two rel ated genes, CYP6B1v3 and CYP6B3v2. Except for CYP6B3v2, the substrate specificity of which has not yet been defined, each of the encoded cyt ochrome P450 monooxygenases (P450s) metabolizes an array of linear fur anocoumarins. All four genes are transcriptionally induced in larvae b y exposure to the furanocoumarin xanthotoxin; several are also induced by other furanocoumarins. Comparisons of the organizational structure s of these genes indicate that all have the same intron/exon arrangeme nt, Sequences in the promoter regions of the P. glaucus CYP6B4v2/CYP6B 5v1 genes and the P. polyxenes CYP6B3v2 gene are similar but not ident ical to the -146 to -97 region of CYP6B1v3 gene, which contains a xant hotoxin-responsive element (XRE-xan) important for basal and xanthotox in-inducible transcription of CYP6B1v3. Complements of the xenobiotic- responsive element (XRE-AhR) in the dioxin-inducible human and rat CYP 1A1 genes also exist in all four promoters, suggesting that these gene s may be regulated by dioxin. Antioxidant-responsive elements (AREs) i n mouse and rat glutathione S-transferase genes and the Barbie box ele ment (Bar) in the bacterial CYP102 gene exist in the CYP6B1v3, CYP6B4v 2, and CYP6B5v1 promoters. Similarities in the protein sequences, intr on positions, and xanthotoxin- and xenobiotic-responsive promoter elem ents indicate that these insect CYP6B genes are derived from a common ancestral gene. Evolutionary comparisons between these P450 genes are the first available for a group of insect genes transcriptionally regu lated by hostplant allelochemicals and provide insights into the proce ss by which insects evolve specialized feeding habits.