Independent Duplications of the Acetylcholinesterase Gene Conferring Insecticide Resistance in the Mosquito Culex pipiens

Abstract

Gene duplication is thought to be the main potential source of material for the evolution of new gene functions. Several models have been proposed for the evolution of new functions through duplication, most based on ancient events (Myr). We provide molecular evidence for the occurrence of several (at least 3) independent duplications of the ace-1 locus in the mosquito Culex pipiens, selected in response to insecticide pressure that probably occurred very recently (<40 years ago). This locus encodes the main target of several insecticides, the acetylcholinesterase. The duplications described consist of 2 alleles of ace-1, 1 susceptible and 1 resistant to insecticide, located on the same chromosome. These events were detected in different parts of the world and probably resulted from distinct mechanisms. We propose that duplications were selected because they reduce the fitness cost associated with the resistant ace-1 allele through the generation of persistent, advantageous heterozygosis. The rate of duplication of ace-1 in C. pipiens is probably underestimated, but seems to be rather high.

Study on Resistance of Culex pipiens (Diptera: Culicidae) Populations to Fenitrothion in Northern Tunisia

“…Our results were in agreement with many previous studies that have shown the role offered by the resistant allele, Ace-1, in many areas of the world [34][35][36][37]. …”

High chlorpyrifos resistance in Culex pipiens mosquitoes: strong synergy between resistance genes

“…SR is resistant to OPs and carbamates through insensitive AChE1 and is homozygous for the ace-1 R allele, in the Slab genetic background (Berticat et al, 2002). Ducos is homozygous for the ace-1 D1 allele, a duplicated allele with a susceptible copy and the resistant R copy, in the Slab genetic background (Labbé et al, 2007). HomoVAL is homozygous for the ace-1 V allele (Alout et al, 2009).…”

“…In the mosquito Culex pipiens, various amplified esterases (encoded by the Ester super locus) and two substitutions on the AChE1 (encoded by the ace-1 gene) have been identified; they confer resistance to a large variety of OP and carbamate insecticides. Mutations at the ace-1 gene include the G119S and the F290V substitutions (the R and V alleles, respectively, Weill et al, 2003;Alout et al, 2007), as well as several duplications (D alleles) containing, in tandem, a susceptible copy (S) and a resistant copy (R or V, Labbé et al, 2007;Alout et al, 2009).…”

Adaptive deletion in resistance gene duplications in the malaria vector Anopheles gambiae

“…Copy‐number variations (CNV) are indeed ubiquitous in natural populations (e.g., Freeman et al., 2006). While most of them are probably deleterious (Schrider et al., 2013), they can nonetheless play a crucial role in adaptation and evolution of genome complexity (Assogba et al., 2016; Katju & Bergthorsson, 2013; Kondrashov, 2012; Labbé, Berthomieu et al., 2007; Milesi, Weill, Lenormand, & Labbé, 2017; Schrider & Hahn, 2010). …”

“…On the contrary, heterogeneous duplications seem to be selected because the two alleles they carry can perform two different functions, by fixing the heterozygote advantage without segregation cost (Haldane, 1932; Milesi, Weill et al., 2017; Spofford, 1969). Such duplications have been documented in a few cases of insecticide resistance, the Rdl gene in Drosophila melanogaster (Remnant et al., 2013), or the ace‐1 gene in Anopheles gambiae and Culex pipiens (Assogba et al., 2016; Labbé, Berthomieu et al., 2007; Milesi, Assogba et al., 2017), where they associate one resistance and one susceptible copy of the gene. While still providing some resistance, this association partially alleviates the deleterious pleiotropic effects (or fitness cost) associated with the resistance allele (Assogba et al., 2015; Labbé et al., 2014; Milesi, Weill et al., 2017).…”