Genome Analysis of Cytochrome P450s and Their Expression Profiles in Insecticide Resistant Mosquitoes, Culex quinquefasciatus

Ting Yang,Nannan Liu,Immo A Hansen

doi:10.1371/journal.pone.0029418

Abstract

Here we report a study of the 204 P450 genes in the whole genome sequence of larvae and adult Culex quinquefasciatus mosquitoes. The expression profiles of the P450 genes were compared for susceptible (S-Lab) and resistant mosquito populations, two different field populations of mosquitoes (HAmCq and MAmCq), and field parental mosquitoes (HAmCq G0 and MAmCqG0) and their permethrin selected offspring (HAmCq G8 and MAmCqG6). While the majority of the P450 genes were expressed at a similar level between the field parental strains and their permethrin selected offspring, an up- or down-regulation feature in the P450 gene expression was observed following permethrin selection. Compared to their parental strains and the susceptible S-Lab strain, HAmCqG8 and MAmCqG6 were found to up-regulate 11 and 6% of total P450 genes in larvae and 7 and 4% in adults, respectively, while 5 and 11% were down-regulated in larvae and 4 and 2% in adults. Although the majority of these up- and down-regulated P450 genes appeared to be developmentally controlled, a few were either up- or down-regulated in both the larvae and adult stages. Interestingly, a different gene set was found to be up- or down-regulated in the HAmCqG8 and MAmCqG6 mosquito populations in response to insecticide selection. Several genes were identified as being up- or down-regulated in either the larvae or adults for both HAmCqG8 and MAmCqG6; of these, CYP6AA7 and CYP4C52v1 were up-regulated and CYP6BY3 was down-regulated across the life stages and populations of mosquitoes, suggesting a link with the permethrin selection in these mosquitoes. Taken together, the findings from this study indicate that not only are multiple P450 genes involved in insecticide resistance but up- or down-regulation of P450 genes may also be co-responsible for detoxification of insecticides, insecticide selection, and the homeostatic response of mosquitoes to changes in cellular environment.

Highlights

Cytochrome P450s have long been of particular interest as they are critical for the detoxification and/or activation of xenobiotics such as drugs, pesticides, plant toxins, chemical carcinogens and mutagens
The current study focused on characterizing the expression profiles of these P450 genes from mosquito populations of Cx. quinquefasciatus bearing different phenotypes in response to permethrin in order to pinpoint the key P450 genes involved in insecticide resistance
The Cx. quinquefasciatus P450s fall into four major clans of CYP2, CYP3, CYP4, and mitochondrial (Fig. 1), as do those identified in other insects [36]

Summary

Introduction

Cytochrome P450s have long been of particular interest as they are critical for the detoxification and/or activation of xenobiotics such as drugs, pesticides, plant toxins, chemical carcinogens and mutagens. They are involved in metabolizing endogenous compounds such as hormones, fatty acids, and steroids. Insect cytochrome P450s are known to play an important role in detoxifying exogenous compounds such as insecticides [2,3,4] and plant toxins [5,6]. Insect P450s are known to be an important part of the biosynthesis and degradation pathways of endogenous compounds such as pheromones, 20-hydroxyecdysone, and juvenile hormone (JH) [19,20,21,22,23] and play important roles in insect growth, development, and reproduction

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Conclusion