title: Forty years of erratic insecticide resistance evolution in the mosquito Culex pipiens.
abstract: One view of adaptation is that it proceeds by the slow and steady accumulation of beneficial mutations with small effects. It is difficult to test this model, since in most cases the genetic basis of adaptation can only be studied a posteriori with traits that have evolved for a long period of time through an unknown sequence of steps. In this paper, we show how ace-1, a gene involved in resistance to organophosphorous insecticide in the mosquito Culex pipiens, has evolved during 40 years of an insecticide control program. Initially, a major resistance allele with strong deleterious side effects spread through the population. Later, a duplication combining a susceptible and a resistance ace-1 allele began to spread but did not replace the original resistance allele, as it is sublethal when homozygous. Last, a second duplication, (also sublethal when homozygous) began to spread because heterozygotes for the two duplications do not exhibit deleterious pleiotropic effects. Double overdominance now maintains these four alleles across treated and nontreated areas. Thus, ace-1 evolution does not proceed via the steady accumulation of beneficial mutations. Instead, resistance evolution has been an erratic combination of mutation, positive selection, and the rearrangement of existing variation leading to complex genetic architecture.
authors.affiliation: Equipe Génétique de l'Adaptation, Institut des Sciences de l'Evolution, CNRS Université Montpellier 2, Montpellier, France. Pierrick.Labbe@ed.ac.uk
authors.forename: Pierrick
authors.initials: P
authors.lastname: Labbé
authors.forename: Claire
authors.initials: C
authors.lastname: Berticat
authors.forename: Arnaud
authors.initials: A
authors.lastname: Berthomieu
authors.forename: Sandra
authors.initials: S
authors.lastname: Unal
authors.forename: Clothilde
authors.initials: C
authors.lastname: Bernard
authors.forename: Mylène
authors.initials: M
authors.lastname: Weill
authors.forename: Thomas
authors.initials: T
authors.lastname: Lenormand
mesh_terms: D000483:Alleles; D000818:Animals; D005075:Biological Evolution; D003433:Crosses, Genetic; D003465:Culex / Q000235:genetics* / Q000254:growth & development; D005260:Female; D005298:Fertility; D005602:France; D020440:Gene Duplication; D005787:Gene Frequency; D005843:Geography; D006579:Heterozygote; D006720:Homozygote; D007305:Insecticide Resistance / Q000235:genetics*; D007814:Larva; D008297:Male; D008969:Molecular Sequence Data; D012621:Seasons; D015996:Survival Rate; D013997:Time Factors