Xenobiotic resistance in insects has evolved predominantly by increasing the metabolic capability of detoxificative systems and/or reducing xenobiotic target site sensitivity. In contrast to the limited range of nucleotide changes that lead to target site insensitivity, many molecular mechanisms lead to enhancements in xenobiotic metabolism. The genomic changes that lead to amplification, overexpression, and coding sequence variation in the three major groups of genes encoding metabolic enzymes, i.e., cytochrome P450 monooxygenases (P450s), esterases, and glutathione-S-transferases (GSTs), are the focus of this review. A substantial number of the adaptive genomic changes associated with insecticide resistance that have been characterized to date are transposon mediated. Several lines of evidence suggest that P450 genes involved in insecticide resistance, and perhaps insecticide detoxification genes in general, may share an evolutionary association with genes involved in allelochemical metabolism. Differences in the selective regime imposed by allelochemicals and insecticides may account for the relative importance of regulatory or structural mutations in conferring resistance.

Molecular mechanisms of metabolic resistance to synthetic and natural xenobiotics

The molecular basis of insecticide resistance in mosquitoes.

Mosquito-borne diseases, the most well known of which is malaria, are among the leading causes of human deaths worldwide. Vector control is a very important part of the global strategy for management of mosquito-associated diseases, and insecticide application is the most important component in this effort. However, mosquito-borne diseases are now resurgent, largely because of the insecticide resistance that has developed in mosquito vectors and the drug resistance of pathogens. A large number of studies have shown that multiple, complex resistance mechanisms—in particular, increased metabolic detoxification of insecticides and decreased sensitivity of the target proteins—or genes are likely responsible for insecticide resistance. Gene overexpression and amplification, and mutations in protein-coding-gene regions, have frequently been implicated as well. However, no comprehensive understanding of the resistance mechanisms or regulation involved has yet been developed. This article reviews current knowledg...

Insecticide Resistance in Mosquitoes: Impact, Mechanisms, and Research Directions

This article discusses the insect CYP genes and P450 enzymes. Cytochrome P450, or CYP genes, constitutes one of the largest family of genes, with representatives in virtually all living organisms, from bacteria to protists, plants, fungi, and animals. The multiple functions of insect P450 enzymes, their complex biochemistry, and their toxicological and physiological importance are presented. Physiological functions are not restricted to one branch of the P450 evolutionary tree, and the ramifications that seem typical of “environmental response genes” are found in both microsomal and mitochondrial P450 encoding genes. The CYP3 and CYP4 clans seem the most diverse, and the smaller CYP2 and mitochondrial CYP clans seem to have proportionally more genes found as orthologs across species. There are many physiological functions for P450s that just are not known or suspected. CYP4C7 was shown to be selectively expressed in the corpora allata and to metabolize JH and its precursors to new metabolites.

Insect CYP Genes and P450 Enzymes

4.1 – Insect Cytochrome P450

Factors on the third chromosome affect the level of cyp6a2 and cyp6a8 expression in Drosophila melanogaster.

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Factors on the third chromosome affect the level of cyp6a2 and cyp6a8 expression in Drosophila melanogaster.