Nrf2/Maf-binding-site-containing functional Cyp6a2 allele is associated with DDT resistance in...

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.

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.

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.