The overexpression and variant of CYP6G4 associated with propoxur resistance in the housefly, Musca domestica L.

Abstract

The control of the housefly, Musca domestica, heavily relies on the application of insecticides. Propoxur, a carbamate, has been widely used for vector control. The housefly populations with high propoxur resistance display point mutations and overexpression of acetylcholinesterase. However, the roles of cytochrome P450 monoxygenases (P450s), as important detoxification enzymes, remain poorly understand in the housefly resistant to propoxur. P450s were implied to contribute to propoxur resistance based on the synergism of piperonyl butoxide (PBO) and the increase of P450 enzyme activity in the near-isogenic line propoxur resistant strain (N-PRS). Five P450 genes (CYP6G4, CYP6A25, CYP304A1, CYP6D3, and CYP6A1) by RNA-sequencing comparison were significantly up-regulated in the N-PRS strain with >1035-fold resistance to propoxur. A total of 13 non-synonymous mutations of three P450 genes (CYP6G4, CYP6D3, and CYP6D8) were found in the N-PRS strain. The amino acid substitutions of CYP6D3 and CYP6D8 were probably not resistance-associated single nucleotide polymorphisms (SNPs) because they were also found in the aabys susceptible strain. However, CYP6G4 variant in the N-PRS strain was not found in the aabys strain. The conjoint analysis of mutations and a series of genetic crosses exhibited that the housefly propoxur resistance was strongly associated with the mutations of CYP6G4 gene. Our results suggested that a combination of up-regulated transcript levels and mutations of CYP6G4 contributed to propoxur resistance in the housefly. © 2021 Society of Chemical Industry.