Berticat C

References (18)

Title : Insecticide resistance in Culex pipiens quinquefasciatus and Aedes albopictus mosquitoes from La Reunion Island - Tantely_2010_Insect.Biochem.Mol.Biol_40_317
Author(s) : Tantely ML , Tortosa P , Alout H , Berticat C , Berthomieu A , Rutee A , Dehecq JS , Makoundou P , Labbe P , Pasteur N , Weill M
Ref : Insect Biochemistry & Molecular Biology , 40 :317 , 2010
Abstract : Resistance to insecticides was monitored on Culex pipiens quinquefasciatus mosquitoes collected in twelve localities of La Reunion, a geographically isolated island of the Indian Ocean. This mosquito is of medical concern in the region as a known vector for filariasis and a potential vector for West Nile and Rift Valley Fever viruses. Our bioassays indicated the presence of resistance to all tested insecticides, i.e. organochlorides, organophosphates and pyrethroids. A molecular investigation revealed a higher frequency of resistance genes in the coastal areas compared to elevated rural sites, probably reflecting the different nature of insecticide pressures together with the genetic cost of resistance alleles. A simple molecular test was developed to detect Rdl allele, encoding a gamma-aminobutyric acid (GABA) receptor resistant to dieldrin. Unexpectedly high Rdl frequencies were recorded over the whole island, despite this insecticide having been banned for over 15 years. This resistant allele was also detected for the first time in two samples of Aedes albopictus, a species recently involved in severe Chikungunya epidemics on the island. Rdl selection in these two mosquito species discloses current insecticide pressures in urban areas, from unknown origins, that should be taken into account to develop vector control strategies.
ESTHER : Tantely_2010_Insect.Biochem.Mol.Biol_40_317
PubMedSearch : Tantely_2010_Insect.Biochem.Mol.Biol_40_317
PubMedID: 20188834

Title : Genes conferring resistance to organophosphorus insecticides in Culex pipiens (Diptera: Culicidae) from Tunisia - Ben Cheikh_2009_J.Med.Entomol_46_523
Author(s) : Ben Cheikh R , Berticat C , Berthomieu A , Pasteur N , Ben Cheikh H , Weill M
Ref : Journal of Medical Entomology , 46 :523 , 2009
Abstract : In Tunisia, the mosquito Culex pipiens shows various organophosphate resistance alleles at Ester and ace-1 loci. The characterization and the distribution pattern of these alleles were studied among 20 populations sampled from north to center of Tunisia. At the Ester locus, Ester4, Ester5, and Ester(B12) were present. A new esterase characterized by the same electrophoretic migration as esterase A1 was identified: A13, encoded by Ester(A13) allele. At the ace-1 locus, the presence of the ace-1(R), ace-1(D), and F290V mutated alleles was also detected. A large heterogeneity in allelic frequencies at Ester and ace-1 loci was observed among samples, with a high significant genotypic differentiation considering both loci (F, = 0.077, P < 10(-5)), depicting variations of insecticide treatment intensity between areas. A comparison between populations collected in 1996 and 2005 showed an absence of significant resistance evolution. However, the high frequencies of resistance alleles in 2005 populations suggested that the selection pressures are still important in Tunisia. Strategies for resistance management are discussed in the context of the current knowledge of the Tunisian situation.
ESTHER : Ben Cheikh_2009_J.Med.Entomol_46_523
PubMedSearch : Ben Cheikh_2009_J.Med.Entomol_46_523
PubMedID: 19496423

Title : Comparison of Anopheles gambiae and Culex pipiens acetycholinesterase 1 biochemical properties - Alout_2008_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_150_271
Author(s) : Alout H , Djogbenou L , Berticat C , Chandre F , Weill M
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 150 :271 , 2008
Abstract : Selection of insensitive acetycholinesterase 1 (AChE1) has occurred in several mosquito species controlled with carbamate (CX) and organophosphate (OP) insecticides. In case of pyrethroid resistance, these insecticides represent an alternative for disease vector control program. Their heavy use in agriculture has selected resistant populations of Anopheles gambiae in West Africa. The evolution of resistance has to be studied to prevent, or at least slow down, the spread of resistant mosquito in wild populations. An. gambiae shares the same resistance mechanism to CX and OP insecticides as Culex pipiens, which was attributed to the G119S substitution in the AChE1 enzyme. By comparing resistant AChE1 from both species, we show here that similar resistance levels are obtained toward 10 insecticides of both classes. Moreover, similar AChE1 activity levels are recorded between either susceptible or resistant mosquitoes of both species. Enzymes belonging to both species seem thus to share identical properties. Consequently, we hypothesize that fitness cost associated with AChE1 insensitivity in C. pipiens mosquitoes should be similar in An. gambiae and thus be used in strategies to control resistant populations where malaria is prevalent.
ESTHER : Alout_2008_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_150_271
PubMedSearch : Alout_2008_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_150_271
PubMedID: 18455457

Title : Characterization of a novel high-activity esterase in Tunisian populations of the mosquito Culex pipiens - Ben_2008_J.Econ.Entomol_101_484
Author(s) : Ben Cheikh R , Berticat C , Berthomieu A , Pasteur N , Ben Cheikh H , Weill M
Ref : J Econ Entomol , 101 :484 , 2008
Abstract : AIn the mosquito Culex pipiens (L.) (Diptera: Culicidae) esterases contribute to insecticide resistance by their increased activity. These esterases display a heterogeneous geographical distribution, particularly in Tunisia, where they are very diverse. In this study, we extended the characterization of a highly active esterase first detected in 1996: B12. Esterase B12 displayed the fastest electrophoretic mobility of all the previously described highly active esterases. We showed that it was encoded by the Ester(B12) allele at the Ester locus, and we isolated a strain, TunB12, homozygous for this allele. TunB12 displayed a low (approximately two- to three-fold) but significant resistance to the organophosphates temephos and chlorpyrifos, and to the pyrethroid permethrin. Only temephos resistance was synergized by S,S,S-tributyl-phosphorotrithioate. Real-time quantitative polymerase chain reaction revealed that the Ester(B12) allele was not amplified in TunB12 strain, indicating that B12 high activity could be due to a gene up-regulation mechanism. Ester(B12) allele frequencies also were estimated in 20 Tunisian populations collected in 2005. Analyses revealed a large distribution of this allele all over the country. Finally, sequences of Ester(B12) were acquired and genetic distance trees were constructed with the resistance Ester alleles already published, providing indications about allele's origins. The diverse array of highly active esterases in C. pipiens from Tunisia and the possible scenario of the origin of their coding alleles are discussed in the context of their possible evolution.
ESTHER : Ben_2008_J.Econ.Entomol_101_484
PubMedSearch : Ben_2008_J.Econ.Entomol_101_484
PubMedID: 18459415

Title : Costs and benefits of multiple resistance to insecticides for Culex quinquefasciatus mosquitoes - Berticat_2008_BMC.Evol.Biol_8_104
Author(s) : Berticat C , Bonnet J , Duchon S , Agnew P , Weill M , Corbel V
Ref : BMC Evol Biol , 8 :104 , 2008
Abstract : BACKGROUND: The evolutionary dynamics of xenobiotic resistance depends on how resistance mutations influence the fitness of their bearers, both in the presence and absence of xenobiotic selection pressure. In cases of multiple resistance, these dynamics will also depend on how individual resistance mutations interact with one another, and on the xenobiotics applied against them. We compared Culex quinquefasciatus mosquitoes harbouring two resistance alleles ace-1R and KdrR (conferring resistance to carbamate and pyrethroid insecticides, respectively) to mosquitoes bearing only one of the alleles, or neither allele. Comparisons were made in environments where both, only one, or neither type of insecticide was present.
RESULTS: Each resistance allele was associated with fitness costs (survival to adulthood) in an insecticide-free environment, with the costs of ace-1R being greater than for KdrR. However, there was a notable interaction in that the costs of harbouring both alleles were significantly less than for harbouring ace-1R alone. The two insecticides combined in an additive, synergistic and antagonistic manner depending on a mosquito's resistance status, but were not predictable based on the presence/absence of either, or both mutations. CONCLUSION: Insecticide resistance mutations interacted to positively or negatively influence a mosquito's fitness, both in the presence or absence of insecticides. In particular, the presence of the KdrR mutation compensated for the costs of the ace-1R mutation in an insecticide-free environment, suggesting the strength of selection in untreated areas would be less against mosquitoes resistant to both insecticides than for those resistant to carbamates alone. Additional interactions suggest the dynamics of resistance will be difficult to predict in populations where multiple resistance mutations are present or that are subject to treatment by different xenobiotics.
ESTHER : Berticat_2008_BMC.Evol.Biol_8_104
PubMedSearch : Berticat_2008_BMC.Evol.Biol_8_104
PubMedID: 18397515

Title : Independent duplications of the acetylcholinesterase gene conferring insecticide resistance in the mosquito Culex pipiens - Labbe_2007_Mol.Biol.Evol_24_1056
Author(s) : Labbe P , Berthomieu A , Berticat C , Alout H , Raymond M , Lenormand T , Weill M
Ref : Molecular Biology Evolution , 24 :1056 , 2007
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.
ESTHER : Labbe_2007_Mol.Biol.Evol_24_1056
PubMedSearch : Labbe_2007_Mol.Biol.Evol_24_1056
PubMedID: 17283366
Gene_locus related to this paper: culpi-ACHE1 , culqu-ACHE1

Title : Different amino-acid substitutions confer insecticide resistance through acetylcholinesterase 1 insensitivity in Culex vishnui and Culex tritaeniorhynchus (Diptera: Culicidae) from China - Alout_2007_J.Med.Entomol_44_463
Author(s) : Alout H , Berthomieu A , Cui F , Tan Y , Berticat C , Qiao C , Weill M
Ref : Journal of Medical Entomology , 44 :463 , 2007
Abstract : Insecticide resistance owing to insensitive acetylcholinesterase (AChE)1 has been reported in several mosquito species, and only two mutations in the ace-1 gene have been implicated in resistance: 119S and 331W substitutions. We analyzed the AChE1 resistance status of Culex vishnui (Theobald) and Culex tritaeniorhynchus Giles sampled in various regions of China. These two species displayed distinct mutations leading to AChE1 insensitivity; the 119S substitution in resistant C. vishnui mosquitoes and the 331W substitution in resistant C. tritaeniorhynchus. A biochemical test was validated to detect the 331W mutation in field samples. The comparison of the recombinant G119S and 331W mutant proteins produced in vitro with the AChE1 extracted from resistant mosquitoes indicated that the AChE1 insensitivity observed could be specifically attributed to these substitutions. Comparison of their biochemical characteristics indicated that the resistance conferred by these mutations depends on the insecticide used, regardless of its class. This resistance seemed to be fixed in the Cx. tritaeniorhynchus populations sampled in a 2000-km transect, suggesting a very high level of insecticide application or a low fitness cost associated with this 331W mutation.
ESTHER : Alout_2007_J.Med.Entomol_44_463
PubMedSearch : Alout_2007_J.Med.Entomol_44_463
PubMedID: 17547232
Gene_locus related to this paper: culpi-ACHE1

Title : Forty years of erratic insecticide resistance evolution in the mosquito Culex pipiens - Labbe_2007_PLoS.Genet_3_e205
Author(s) : Labbe P , Berticat C , Berthomieu A , Unal S , Bernard C , Weill M , Lenormand T
Ref : PLoS Genet , 3 :e205 , 2007
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.
ESTHER : Labbe_2007_PLoS.Genet_3_e205
PubMedSearch : Labbe_2007_PLoS.Genet_3_e205
PubMedID: 18020711
Gene_locus related to this paper: culqu-ACHE1

Title : High Wolbachia density correlates with cost of infection for insecticide resistant Culex pipiens mosquitoes - Duron_2006_Evolution_60_303
Author(s) : Duron O , Labbe P , Berticat C , Rousset F , Guillot S , Raymond M , Weill M
Ref : Evolution , 60 :303 , 2006
Abstract : In the mosquito Culex pipiens, insecticide resistance genes alter many life-history traits and incur a fitness cost. Resistance to organophosphate insecticides involves two loci, with each locus coding for a different mechanism of resistance (degradation vs. insensitivity to insecticides). The density of intracellular Wolbachia bacteria has been found to be higher in resistant mosquitoes, regardless of the mechanism involved. To discriminate between costs of resistance due to resistance genes from those associated with elevated Wolbachia densities, we compared strains of mosquito sharing the same genetic background but differing in their resistance alleles and Wolbachia infection status. Life-history traits measured included strength of insecticide resistance, larval mortality, adult female size, fecundity, predation avoidance, mating competition, and strength of cytoplasmic incompatibility (CI). We found that: (1) when Wolbachia are removed, insecticide resistance genes still affect some life-history traits; (2) Wolbachia are capable of modifying the cost of resistance; (3) the cost of Wolbachia infections increases with their density; (4) different interactions occurred depending on the resistance alleles involved; and (5) high densities of Wolbachia do not increase the strength of CI or maternal transmission efficiency relative to low Wolbachia densities. Insecticide resistance genes generated variation in the costs of Wolbachia infections and provided an interesting opportunity to study how these costs evolve, a process generally operating when Wolbachia colonizes a new host.
ESTHER : Duron_2006_Evolution_60_303
PubMedSearch : Duron_2006_Evolution_60_303
PubMedID: 16610322

Title : Acetylcholinesterase genes within the Diptera: takeover and loss in true flies - Huchard_2006_Proc.Biol.Sci_273_2595
Author(s) : Huchard E , Martinez M , Alout H , Douzery EJ , Lutfalla G , Berthomieu A , Berticat C , Raymond M , Weill M
Ref : Proc Biol Sci , 273 :2595 , 2006
Abstract : It has recently been reported that the synaptic acetylcholinesterase (AChE) in mosquitoes is encoded by the ace-1 gene, distinct and divergent from the ace-2 gene, which performs this function in Drosophila. This is an unprecedented situation within the Diptera order because both ace genes derive from an old duplication and are present in most insects and arthropods. Nevertheless, Drosophila possesses only the ace-2 gene. Thus, a secondary loss occurred during the evolution of Diptera, implying a vital function switch from one gene (ace-1) to the other (ace-2). We sampled 78 species, representing 50 families (27% of the Dipteran families) spread over all major subdivisions of the Diptera, and looked for ace-1 and ace-2 by systematic PCR screening to determine which taxonomic groups within the Diptera have this gene change. We show that this loss probably extends to all true flies (or Cyclorrhapha), a large monophyletic group of the Diptera. We also show that ace-2 plays a non-detectable role in the synaptic AChE in a lower Diptera species, suggesting that it has non-synaptic functions. A relative molecular evolution rate test showed that the intensity of purifying selection on ace-2 sequences is constant across the Diptera, irrespective of the presence or absence of ace-1, confirming the evolutionary importance of non-synaptic functions for this gene. We discuss the evolutionary scenarios for the takeover of ace-2 and the loss of ace-1, taking into account our limited knowledge of non-synaptic functions of ace genes and some specific adaptations of true flies.
ESTHER : Huchard_2006_Proc.Biol.Sci_273_2595
PubMedSearch : Huchard_2006_Proc.Biol.Sci_273_2595
PubMedID: 17002944
Gene_locus related to this paper: culpi-ACHE1 , culpi-ACHE2 , drobs-ACHE2 , drosi-ACHE , drowi-ACHE , gloff-ACHE2

Title : Insecticide resistance: a silent base prediction -
Author(s) : Weill M , Berthomieu A , Berticat C , Lutfalla G , Negre V , Pasteur N , Philips A , Leonetti JP , Fort P , Raymond M
Ref : Current Biology , 14 :R552 , 2004
PubMedID: 15268871

Title : Parasitism increases and decreases the costs of insecticide resistance in mosquitoes - Agnew_2004_Evolution_58_579
Author(s) : Agnew P , Berticat C , Bedhomme S , Sidobre C , Michalakis Y
Ref : Evolution , 58 :579 , 2004
Abstract : Adaptations conferring resistance to xenobiotics (antibiotics, insecticides, herbicides, etc.) are often costly to the organism's fitness in the absence of the selecting agent. In such conditions, and unless other mutations compensate for the costs of resistance, sensitive individuals are expected to out-reproduce resistant individuals and drive resistance alleles to a low frequency, with the rate and magnitude of this decline being proportional to the costs of resistance. However, this evolutionary dynamic is open to modification by other sources of selection acting on the relative fitness of susceptible and resistant individuals. Here we show parasitism not only as a source of selection capable of modifying the costs of organophosphate insecticide resistance in mosquitoes, but also that qualitatively different interactions (increasing or decreasing the relative fitness of resistant individuals) occurred depending on the particular form of resistance involved. As estimates of the parasite's fitness also varied according to its host's form of resistance, our data illustrate the potential for epidemiological feedbacks to influence the strength and direction of selection acting on resistance mutations in untreated environments.
ESTHER : Agnew_2004_Evolution_58_579
PubMedSearch : Agnew_2004_Evolution_58_579
PubMedID: 15119441

Title : Insecticide resistance genes confer a predation cost on mosquitoes, Culex pipiens - Berticat_2004_Genet.Res_83_189
Author(s) : Berticat C , Duron O , Heyse D , Raymond M
Ref : Genetical Research , 83 :189 , 2004
Abstract : Newly occurring adaptive genes, such as those providing insecticide resistance, display a fitness cost which is poorly understood. In order to detect subtle behavioural changes induced by the presence of resistance genes, we used natural predators and compared their differential predation on susceptible and resistant Culex pipiens mosquitoes, using strains with a similar genetic background. Resistance genes were either coding an overproduced detoxifying esterase (locus Ester), or an insensitive target (locus ace-1). Differential predation was measured between susceptible and resistant individuals, as well as among resistant mosquitoes. A backswimmer, a water measurer, a water boatman and a predaceous diving beetle were used as larval predators, and a pholcid spider as adult predator. Overall, the presence of a resistance gene increased the probability of predation: all resistance genes displayed predation costs relative to susceptible ones, at either the larval or adult stage, or both. Interestingly, predation preferences among the susceptible and the resistance genes were not ranked uniformly. Possible explanations for these results are given, and we suggest that predators, which are designed by natural selection to detect specific behavioural phenotypes, are useful tools to explore non-obvious differences between two classes of individuals, for example when they differ by the presence or absence of one recent gene, such as insecticide resistance genes.
ESTHER : Berticat_2004_Genet.Res_83_189
PubMedSearch : Berticat_2004_Genet.Res_83_189
PubMedID: 15462412

Title : Comparative genomics: Insecticide resistance in mosquito vectors - Weill_2003_Nature_423_136
Author(s) : Weill M , Lutfalla G , Mogensen K , Chandre F , Berthomieu A , Berticat C , Pasteur N , Philips A , Fort P , Raymond M
Ref : Nature , 423 :136 , 2003
Abstract : Resistance to insecticides among mosquitoes that act as vectors for malaria (Anopheles gambiae) and West Nile virus (Culex pipiens) emerged more than 25 years ago in Africa, America and Europe; this resistance is frequently due to a loss of sensitivity of the insect's acetylcholinesterase enzyme to organophosphates and carbamates1. Here we show that this insensitivity results from a single amino-acid substitution in the enzyme, which we found in ten highly resistant strains of C. pipiens from tropical (Africa and Caribbean) and temperate (Europe) areas, as well as in one resistant African strain of A. gambiae. Our identification of this mutation may pave the way for designing new insecticides.
ESTHER : Weill_2003_Nature_423_136
PubMedSearch : Weill_2003_Nature_423_136
PubMedID: 12736674
Gene_locus related to this paper: anoga-ACHE1 , culpi-ACHE1

Title : High Wolbachia density in insecticide-resistant mosquitoes - Berticat_2002_Proc.Biol.Sci_269_1413
Author(s) : Berticat C , Rousset F , Raymond M , Berthomieu A , Weill M
Ref : Proc Biol Sci , 269 :1413 , 2002
Abstract : Wolbachia symbionts are responsible for various alterations in host reproduction. The effects of the host genome on endosymbiont levels have often been suggested, but rarely described. Here, we show that Wolbachia density is strongly modified by the presence of insecticide-resistant genes in the common house mosquito, Culex pipiens. The Wolbachia density was estimated using a real-time quantitative PCR assay. Strains harbouring different genes conferring resistance were more infected than a susceptible strain with the same genetic background. We show that this interaction also operates in natural populations. We propose that mosquitoes may control Wolbachia density less efficiently when they carry an insecticide-resistant gene, i.e. when they suffer from a physiological resistance cost.
ESTHER : Berticat_2002_Proc.Biol.Sci_269_1413
PubMedSearch : Berticat_2002_Proc.Biol.Sci_269_1413
PubMedID: 12079666

Title : Recombination between two amplified esterase alleles in Culex pipiens - Berticat_2001_J.Hered_92_349
Author(s) : Berticat C , Marquine M , Raymond M , Chevillon C
Ref : Journal of Heredity , 92 :349 , 2001
Abstract : Esterase gene amplification at the Ester superlocus provides organophosphate resistance in the mosquito Culex pipiens (L.). In this study we explored the possibility of recombination between two amplified esterase alleles, thus generating a composite amplified allele. To do that, females heterozygous for two distinct amplified alleles (Ester(2) and Ester(4)) were crossed with males homozygous for a third resistance allele (Ester(8)). Among analyzed offspring, one recombinant composite allele (Ester(2-4)) was detected, providing a rate of recombination of approximately 0.2%. This is the first report of a recombination between two distinct amplified esterase alleles. This phenomenon renders the predictability of allele evolution considerably more complex than was previously thought.
ESTHER : Berticat_2001_J.Hered_92_349
PubMedSearch : Berticat_2001_J.Hered_92_349
PubMedID: 11535649

Title : Insecticide resistance in the mosquito culex pipiens: what have we learned about adaptation? - Raymond_2001_Genetica_112-113_287
Author(s) : Raymond M , Berticat C , Weill M , Pasteur N , Chevillon C
Ref : Genetica , 112-113 :287 , 2001
Abstract : Resistance to organophosphate (OP) insecticide in the mosquito Culex pipiens has been studied for ca. 30 years. This example of micro-evolution has been thoroughly investigated as an opportunity to assess precisely both the new adapted phenotypes and the associated genetic changes. A notable feature is that OP resistance is achieved with few genes, and these genes have generally large effects. The molecular events generating such resistance genes are complex (e.g., gene amplification, gene regulation) potentially explaining their low frequency of de novo occurrence. In contrast, migration is a frequent event, including passive transportation between distant populations. This generates a complex interaction between mutations and migration, and promotes competition among resistance alleles. When the precise physiological action of each gene product is rather well known, it is possible to understand the dominance level or the type of epistasis observed. It is however difficult to predict a priori how resistance genes will interact, and it is too early to state whether or not this will be ever possible. These resistance genes are costly, and the cost is variable among them. It is usually believed that the initial fitness cost would gradually decrease due to subsequent mutations with a modifier effect. In the present example, a particular modifier occurred (a gene duplication) at one resistance locus, whereas at the other one reduction of cost is driven by allele replacement and apparently not by selection of modifiers.
ESTHER : Raymond_2001_Genetica_112-113_287
PubMedSearch : Raymond_2001_Genetica_112-113_287
PubMedID: 11838771

Title : Quantitative polymerase chain reaction to estimate the number of amplified esterase genes in insecticide-resistant mosquitoes -
Author(s) : Weill M , Berticat C , Raymond M , Chevillon C
Ref : Analytical Biochemistry , 285 :267 , 2000
PubMedID: 11017713