MOLECULAR-CLONING OF A FAMILY OF XENOBIOTIC-INDUCIBLE DROSOPHILID CYTOCHROME P450S - EVIDENCE FOR INVOLVEMENT IN HOST-PLANT ALLELOCHEMICAL RESISTANCE

Cytochrome P450s constitute a superfamily of genes encoding mostly mic rosomal hemoproteins that play a dominant role in the metabolism of a wide variety of both endogenous and foreign compounds, In insects, xen obiotic metabolism (i.e., metabolism of insecticides and toxic natural plant compounds) is known to involve members of the CYP6 family of cy tochrome P450s. Use of a 3' RACE (rapid amplification of cDNA ends) st rategy with a degenerate primer based on the conserved cytochrome P450 heme-binding decapeptide loop resulted in the amplification of four c DNA sequences representing another family of cytochrome P450 genes (CW 28) from two species of isoquinoline alkaloid-resistant Drosophila and the cosmopolitan species Drosophila hydei, The CW28 family forms a mo nophyletic clade with strong regional homologies to the vertebrate CYP 3 family and the insect CYP6 family (both of which are involved in xen obiotic metabolism) and to the insect CYP9 family (of unknown function ), Induction of mRNA levels for three of the CYP28 cytochrome P450s by toxic host-plant allelochemicals (up to 11.5-fold) and phenobarbital (up to 49-fold) corroborates previous in vitro metabolism studies and suggests a potentially important role for the CYP28 family in determin ing patterns of insect-host-plant relationships through xenobiotic det oxification.