Genomic Analysis of Detoxification Supergene Families in the Mosquito Anopheles sinensis

Abstract

Anopheles sinensis is an important malaria vector in China and other Southeast Asian countries, and the emergence of insecticide resistance in this mosquito poses a serious threat to the efficacy of malaria control programs. The recently published An. sinensis genome and transcriptome provide an opportunity to understand the molecular mechanisms of insecticide resistance. Analysis of the An. sinensis genome revealed 174 detoxification genes, including 93 cytochrome P450s (P450s), 31 glutathione-S-transferases (GSTs), and 50 choline/carboxylesterases (CCEs). The gene number was similar to that in An. gambiae, but represented a decrease of 29% and 42% compared with Aedes aegypti and Culex quinquefasciatus, respectively. The considerable contraction in gene number in Anopheles mosquitoes mainly occurred in two detoxification supergene families, P450s and CCEs. The available An. sinensis transcriptome was also re-analyzed to further identify key resistance-associated detoxification genes. Among 174 detoxification genes, 124 (71%) were detected. Several candidate genes overexpressed in a deltamethrin-resistant strain (DR-strain) were identified as belonging to the CYP4 or CYP6 family of P450s and the Delta GST class. These generated data provide a basis for identifying the resistance-associated genes of An. sinensis at the molecular level.

Fig 1. The phylogenetic analysis of cytochrome P450s, glutathione-S-transferases and choline/carboxylesterases.

(A) Unrooted distance neighbor-joining tree showing the phylogeny of cytochrome P450s from the genomes of Anopheles sinensis (red circle), Aedes aegypti (green square) and Culex pipiens quinquefasciatusin (aqua triangle). (B) Unrooted distance neighbor-joining tree showing the phylogeny of glutathione-S-transferases from the genomes of Anopheles sinensis (red circle), Anopheles gambiae (blue triangle), Aedes aegypti (green square), Culex pipiens quinquefasciatusin (aqua triangle) and Drosophila melanogaster (pink rhombus). (C) Unrooted distance neighbor-joining tree showing the phylogeny of choline/carboxylesterases from the genome of Anopheles sinensis (red circle), Aedes aegypti (green square) and Culex pipiens quinquefasciatusin (aqua triangle). The percentage of bootstrap confidence values greater than 70% (1000 replicates) is indicated at the nodes.

Fig 2. The phylogenetic analysis of glutathione-S-transferases.

Unrooted distance neighbor-joining tree showing the phylogeny of glutathione-S-transferases from the genomes of Anopheles sinensis (red circle) and Anopheles gambiae (blue triangle). The percentage of bootstrap confidence values greater than 70% (1000 replicates) is indicated at the nodes.

Fig 3. The phylogenetic analysis of α-esterases.

Unrooted distance neighbor-joining tree showing the phylogeny of α-esterases from the genomes of Anopheles sinensis (red circle), Anopheles gambiae (blue triangle), Aedes aegypti (green square), Culex pipiens quinquefasciatusin (aqua triangle) and Drosophila melanogaster (aqua triangle). The percentage of bootstrap confidence values greater than 70% (1000 replicates) is indicated at the nodes.