Nrf2/Maf‐binding‐site‐containing functional Cyp6a2 allele is associated with DDT resistance in Drosophila melanogaster

BACKGROUND Increased insecticide detoxification mediated by cytochrome P450s is a common mechanism of insecticide resistance. Although Cyp6a2 has been observed to be overexpressed in many 4,4′‐dichlorodiphenyltrichloroethane ( DDT )‐resistant strains of Drosophila melanogaster , how Cyp6a2 is regulated and whether its overproduction confers DDT resistance remain elusive . RESULTS Molecular analysis identified five Cyp6a2 alleles ( Cyp6a2 Canton −S‐1 , Cyp6a2 Canton −S‐2 , Cyp6a2 91‐C , Cyp6a2 91‐R and Cyp6a2 Wisconsin − WD ) from four D. melanogaster strains, notably differing in the presence or absence of an intact Nrf2/Maf (a transcription factor) binding site in the 5′‐promoter core region, a ‘ G1410 ’ frameshift deletion mutation in the heme‐binding region and a long terminal repeat ( LTR ) of transposable element 17.6 in the 3′‐untranslated region ( UTR ). Linkage analysis confirmed that DDT resistance was genetically linked to a Nrf2/Maf‐binding‐site‐containing, LTR ‐lacking functional allele of Cyp6a2 ( Cyp6a2 91‐R ). The qRT‐PCR results showed that overexpression of functional Cyp6a2 was consistently associated with DDT resistance. Luciferase reporter gene assays revealed that an intact Nrf2/Maf binding site in the 5′‐promoter core region enhanced the constitutive transcription of Cyp6a2 . CONCLUSION The results suggest that the Nrf2/Maf binding‐site‐containing functional Cyp6a2  allele is associated with DDT resistance in the D. melanogaster strains under study. © 2013 Society of Chemical Industry