The variation of a cytochrome P450 gene, CYP6G4, drives the evolution of Musca domestica L. (Diptera: Muscidae) resistance to insecticides in China

Long term and excessive insecticide use has resulted in some environmental problems and especially, insecticide resistance evolution in insect pests. The variation of cytochrome P450 monooxygenases (P450s), associated with the metabolic detoxification of toxic xenobiotics, is often involved in insecticide resistance. Here, we found that the variation in a P450 gene, CYP6G4, is the most important driver of carbamates resistance in the house fly (Musca domestica). Deciphering the detailed molecular mechanisms of the insecticide resistance is critical for performing suitable insecticide resistance management strategies. Our research results revealed that the com-bination of amino acid mutations (110C-330E-360N/S, 110C-330E-360S) of CYP6G4 could improve the resis-tance to propoxur. The nucleotide variations in the promoter region of CYP6G4 significantly increased the luciferase activity by the reporter gene assays. Additionally, miR-281-1-5p was confirmed to post-transcriptionally down-regulate the expression of CYP6G4. These findings suggest that three independent mechanisms; amino acid mutations of the P450 protein, mutations in the promoter region and low expression of post-trans-regulatory factors, as the powerful strategies for the insect resistance to toxic compounds, play a crucial role in the evolutionary processes of insecticide resistance.