, Volume 112, Issue 1, pp 287–296 | Cite as

Insecticide resistance in the mosquito Culex pipiens: what have we learned about adaptation?

  • Michel Raymond
  • Claire Berticat
  • Mylène Weill
  • Nicole Pasteur
  • Christine Chevillon


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.

dominance epistasis fitness cost gene amplification insecticide resistance selection 


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  1. Berticat, C., Boquien, G., Raymond, M. & C. Chevillon, 2001. Insecticide resistance genes induce a mating competition cost in Culex pipiens mosquitoes. Genet. Res. (in press).Google Scholar
  2. Berticat, C., M.-P. Dubois, M. Marquine, C. Chevillon & M. Raymond, 2000. A molecular test to identify resistance alleles at the Ester super locus in the mosquito Culex pipiens. Pest Manag. Sc. 56: 727–731.Google Scholar
  3. Bost, B., C. Dillman & D. de Vienne, 1999. Fluxes and metabolic pools as model traits for quantitative genetics: 1. the L-shaped distribution of gene effects. Genetics 153: 2001–2012.Google Scholar
  4. Bourguet D., R. Capela & M. Raymond, 1996. An insensitive acetylcholinesterase in Culex pipiens L. mosquitoes from Portugal. J. Econ. Entomol. 89: 1060–1066.Google Scholar
  5. Bourguet, D., T. Lenormand, T. Guillemaud, V. Marcel & M. Raymond, 1997a. Variation of dominance of newly arisen adaptive genes. Genetics 147: 1225–1234.Google Scholar
  6. Bourguet, D. & M. Raymond, 1998. The molecular basis of dominance relationships: the case of some recent adaptive genes. J. Evol. Biol. 11: 103–122.Google Scholar
  7. Bourguet, D., M. Raymond, S. Berrada & D. Fournier, 1997b. Interaction between acetylcholinesterase and choline acetyltransferase: an hypothesis to explain unusual toxicological responses. Pest. Sc. 51: 276–282.Google Scholar
  8. Callaghan, A., T. Guillemaud, N. Makate & M. Raymond, 1998. Polymorphism and fluctuations in copy number of amplified esterase genes in Culex pipiens mosquitoes. Insect Mol. Biol. 7: 295–300.Google Scholar
  9. Chevillon, C., G. Addis, M. Raymond & A. Marchi, 1995a. Population structure in Mediterranean islands and risk of genetic invasion in Culex pipiens. Biol. J. Linn. Soc. 55: 329–343.Google Scholar
  10. Chevillon, C., D. Bourguet, F. Rousset, N. Pasteur & M. Raymond, 1997. Pleiotropy of adaptive changes in populations: comparisons among insecticide resistance genes in Culex pipiens. Genet. Res. 68: 195–203.Google Scholar
  11. Chevillon, C., N. Pasteur, M. Marquine, D. Heyse & M. Raymond, 1995b. Population structure and dynamics of selected genes in the mosquito Culex pipiens. Evolution 49: 997–1007.Google Scholar
  12. Chevillon, C., M. Raymond, T. Guillemaud, T. Lenormand & N. Pasteur, 1999. Population genetics of insecticide resistance in the mosquito Culex pipiens. Biol. J. Linn. Soc. 68: 147–157.Google Scholar
  13. Clark, A.G. & L. Wang, 1997. Epistasis in measured genotypes: Drosophila P-element insertions. Genetics 147: 157–163.Google Scholar
  14. Clarke, G.M., J.L. Yen & J.A. McKenzie, 2000. Wings and bristles: character specificity of the asymmetry phenotype in insecticideresistant strains of Lucilia cuprina. Proc. R. Soc. Lond. B 267: 1815–1818.Google Scholar
  15. Coyne, J.A., N.H. Barton & M. Turelli, 1997. Perspective: a critique of sewall wright' shifting balance theory of evolution. Evolution 51: 643–671.Google Scholar
  16. Curtis, C.F. & N. Pasteur, 1981. Organophosphate resistance in vector populations of the complex Culex pipiens L. (Diptera, Culicidae). Bull. Ent. Res. 71: 153–161.Google Scholar
  17. Curtis, C.F. & G.B. White, 1984. Plasmodium falciparum transmission in England: entomological and epidemiological data relative to cases in 1983. J. Trop. Med. Hyg. 87: 101–114.Google Scholar
  18. Davies, A.G., A.Y. Game, Z. Chen, T.J. Williams, S. Goodall, J.L. Yen, J.A. McKenzie & P. Batterham, 1996. Scalloped wings is the Lucilia cuprina Notch homologue and a candidate for the Modifier of fitness and asymmetry of diazinon resistance. Genetics 143: 1321–1337.Google Scholar
  19. de Visser, J.A.G.M., R.F. Hoekstra & H. Van den Ende, 1997. Test of interaction between genetic markers that affect fitness in Aspergillus niger. Evolution 51: 1499–1505.Google Scholar
  20. Elena, S.F. & R.E. Lenski, 1997. Test of synergistic interactions among deleterious mutations in bacteria. Nature 390: 395–398.Google Scholar
  21. Eritja, R. & C. Chevillon, 1999. Interruption of chemical control and evolution of insecticide resistance genes in Culex pipiens. J. Med. Entomol. 36: 41–49.Google Scholar
  22. Fournier, D. & A. Mutero, 1994. Modification of acetylcholinesterase as a mechanism of resistance to insecticides. Comp. Biochem. Physiol. 108C: 19–31.Google Scholar
  23. Gazave, E., C. Chevillon, T. Lenormand, M. Marquine & M. Raymond, 2001. Dissecting the cost of insecticide resistance genes during the overwintering period of the mosquito Culex pipiens Heredity 87: 1–8.Google Scholar
  24. Georghiou, G. & N. Pasteur, 1978. Electrophoretic esterase patterns in insecticide-resistant and susceptible mosquitoes. J. Econ. Entomol. 71: 201–205.Google Scholar
  25. Guillemaud, T., T. Lenormand, D. Bourguet, C. Chevillon, N. Pasteur & M. Raymond, 1998. Evolution of resistance in Culex pipiens: allele replacement and changing environment. Evolution 52: 430–440.Google Scholar
  26. Guillemaud, T., N. Makate, M. Raymond, B. Hirst & A. Callaghan, 1997. Esterase gene amplification in Culex pipiens. Insect Mol. Biol. 6: 319–327.Google Scholar
  27. Guillemaud, T., S. Rooker, N. Pasteur & M. Raymond, 1996. Testing the unique amplification event and the worldwide migration hypothesis of insecticide resistance genes with sequence data. Heredity 77: 535–543.Google Scholar
  28. Haldane, J.B.S., 1924. A mathematical theory of natural and artificial selection: Part I. Cambridge Phil. Soc. Trans. 23: 19–41.Google Scholar
  29. Highton, R.B. & E.C.C. van Someren, 1970. The transportation of mosquitoes between international airports. Bull. Wld Hlth Org. 42: 334–335.Google Scholar
  30. Hilbish, T.J., B.L. Bayne & A. Day, 1994. Genetics of physiological differentiation within the marine mussel genus Mytilus. Evolution 48: 267–286.Google Scholar
  31. Hoffmann, F., D. Fournier & P. Spierer, 1992. Minigenes rescues acetylcholinesterase lethal mutations in Drosophila melanogaster. J. Mol. Biol. 223: 17–22.Google Scholar
  32. Hughes, A.L., 1994. The evolution of functionally novel proteins after gene duplication. Proc. R. Soc. Lond. B 256: 119–124.Google Scholar
  33. Kacser, H. & J.A. Burns, 1981. The molecular basis of dominance. Genetics 97: 639–666.Google Scholar
  34. Keightley, P.D., 1996. A metabolic basis for dominance and recessivity. Genetics 143: 621–625.Google Scholar
  35. Kelly, J.K., 2000. Epistasis, linkage, and balancing selection, pp. 146–157 in Epistasis and the Evolutionary Process, edited by J.B. Wolf, E.D. Brodie III & M.J. Wade. Oxford University Press, New York.Google Scholar
  36. Lande, R., 1983. The response to selection on major and minor mutations affecting a metrical trait. Heredity 50: 47–65.Google Scholar
  37. Lees, D.R., 1981. Industrial melanism: genetic adaptation of animals to air pollution, pp. 129–176 in Genetic Consequences of Man Made Change, edited by J.A. Bishop & L.M. Cook. Academic Press, London.Google Scholar
  38. Lenormand, T., D. Bourguet, T. Guillemaud & M. Raymond, 1999. Tracking the evolution of insecticide resistance in the mosquito Culex pipiens. Nature 400: 861–864.Google Scholar
  39. Lenormand, T., T. Guillemaud, D. Bourguet & M. Raymond, 1998a. Appearance and sweep of a gene duplication: adaptive response and potential for a new function in the mosquito Culex pipiens. Evolution 52: 1705–1712.Google Scholar
  40. Lenormand, T., T. Guillemaud, D. Bourguet & M. Raymond, 1998b. Evaluating gene flow using selected markers: a case study. Genetics 149: 1383–1392.Google Scholar
  41. Lenormand, T. & M. Raymond, 1998. Resistance management: the stable zone strategy. Proc. R. Soc. Lond. B 65: 1–6.Google Scholar
  42. Lenormand, T. & M. Raymond, 2000. Clines with variable selection and variable migration: model and field studies. Am. Nat. 155: 70–82.Google Scholar
  43. MacNair, M.R., 1991. Why the evolution of resistance to anthropogenic toxins normally involves major gene changes: the limits to natural selection. Genetica 84: 213–219.Google Scholar
  44. McKenzie, J.A., 1996. Ecological and Evolutionary Aspects of Insecticide Resistance. Academic Press, Georgetown, Texas.Google Scholar
  45. Nagylaki, T., 1975. Conditions for the existence of clines. Genetics 80: 595–615.Google Scholar
  46. Orr, H.A., 1998. The population genetics of adaptation: the distribution of factors fixed during adaptive evolution. Evolution 52: 935–949.Google Scholar
  47. Orr, H.A. & J.A. Coyne, 1992. The genetics of adaptation: a reassessment. Am. Nat. 140: 725–742.Google Scholar
  48. Parsch, J., J.A. Russel, I. Beerman, D.L. Hartl & W. Stephan, 2000. Deletion of a conserved regulatory element in the Drosophila Adh gene leads to increased alcohol dehydrogenase activity but also delays development. Genetics 156: 219–227.Google Scholar
  49. Pasteur, N., A. Iseki & G.P. Georghiou, 1981. Genetic and biochemical studies of the highly active esterases A' and B associated with organophosphate resistance in mosquitoes of the Culex pipiens complex. Biochem. Genet. 19: 909–919.Google Scholar
  50. Pasteur, N., M. Marquine, H. Ben Cheikh, C. Bernard & D. Bourguet, 1999. A new mechanism conferring unprecedented high resistance to chlorpyrifos in Culex pipiens (Diptera: Culicidae). J. Med. Entomol. 36: 794–802.Google Scholar
  51. Pasteur, N., M. Marquine, F. Rousset, A.-B. Failloux, C. Chevillon & M Raymond, 1995. The role of passive migration in the dispersal of resistance genes in Culex pipiens quinquefasciatus within french polynesia. Genet. Res. 66: 139–146.Google Scholar
  52. Pasteur, N., M. Marquine, H.H. Tran, S.N. Vu & A.-B. Failloux, 2001. Overproduced esterase in Culex pipiens quinquefasciatus from Vietnam. J. Med. Entomol. 38: 740–745.Google Scholar
  53. Pasteur, N., E. Nancé & N. Bons, 2001. Tissue localization of overproduced esterases in the mosquito Culex pipiens L. J. Med. Entomol. 38 (in press).Google Scholar
  54. Pasteur, N. & G. Sinègre, 1978. Autogenesis versus esterase polymorphism and chlorpyrifos (Dursban) resistance in Culex pipiens pipiens L. Biochem. Genet. 16: 941–943.Google Scholar
  55. Pasteur, N., G. Sinègre & A. Gabinaud, 1981. Est-2 and Est-3 polymorphism in Culex pipiens L. from southern France in relation to organophosphate resistance. Biochem. Genet. 19: 499–508.Google Scholar
  56. Poirié, M., M. Raymond & M. Pasteur, 1992. Identification of two distinct amplifications of the esterase B locus in Culex pipiens (L.) mosquitoes from Mediterranean countries. Biochem. Genet. 30: 13–26.Google Scholar
  57. Qiao, C.-L., M. Marquine, N. Pasteur & M. Raymond, 1998. A new esterase amplification involved in OP resistance in Culex pipiens mosquitoes from China. Biochem. Genet. 36: 417–426.Google Scholar
  58. Qiao, C.-L. & M. Raymond, 1995. The same esterase B1 haplotype is amplified in insecticide resistant mosquitoes of the Culex pipiens complex from the Americas and China. Heredity 74: 339–345.Google Scholar
  59. Raymond, M., A. Callaghan, P. Fort & N. Pasteur, 1991.Worldwide migration of amplified insecticide resistance genes in mosquitoes. Nature 350: 151–153.Google Scholar
  60. Raymond, M., C. Chevillon, T. Guillemaud, T. Lenormand & N. Pasteur, 1998. An overview of the evolution of overproduced esterases in the mosquito Culex pipiens. Phil. Trans. R. Soc. Lond. B 353: 1–5.Google Scholar
  61. Raymond, M., D. Heckel & J.G. Scott, 1989. Interaction between pesticide genes: model and experiment. Genetics 123: 543–551.Google Scholar
  62. Raymond, M. & M. Marquine, 1994. Evolution of insecticide resistance in Culex pipiens populations: the Corsican paradox. J. Evol. Biol. 7: 315–337.Google Scholar
  63. Raymond, M., N. Pasteur, G.P. Georghiou, R.B. Mellon, M.C. Wirth & M.K. Hawley, 1987. Detoxification esterases new to California, USA, in organophosphate-resistant Culex quinquefasciatus (Diptera: Culicidae). J. Med. Entomol. 24: 24–27.Google Scholar
  64. Raymond, M., C.L. Qiao & A. Callaghan, 1996. Esterase polymorphism in insecticide susceptible populations of the mosquito Culex pipiens. Genet. Res. 67: 19–26.Google Scholar
  65. Rivet, Y., M. Marquine & M. Raymond, 1993. French mosquito populations invaded by A2–B2 esterases causing insecticide resistance. Biol. J. Linn. Soc. 49: 249–255.Google Scholar
  66. Rooker, S., T. Guillemaud, J. Bergé, N. Pasteur & M. Raymond, 1996. Coamplification of esterase A and B genes as a single unit in the mosquito Culex pipiens. Heredity 77: 555–561.Google Scholar
  67. Severini, C., R. Romi, M. Marinucci, T. Guillemaud & M. Raymond, 1997. Esterases A5–B5 in organophosphate-resistant Culex pipiens from Italy. Med. Vet. Entomol. 11: 123–126.Google Scholar
  68. Severini, C., R. Romi, M. Marinucci & M. Raymond, 1993. Mechanisms of insecticide resistance in field populations of Culex pipiens from Italy. J. Am. Mosq. Cont. Assoc. 9: 164–168.Google Scholar
  69. Silvestrini, F., C Severini, V. Di Pardo, R. Romi, E. De Matthaeis & M. Raymond, 1998. Population structure and dynamics of insecticide resistance genes in Culex pipiens populations from Italy. Heredity 81: 342–348.Google Scholar
  70. Slatkin, M., 1973. Gene flow and selection in a cline. Genetics 75: 733–756.Google Scholar
  71. Slatkin, M., 1987. Gene flow and the geographic structure of natural populations. Science 236: 787–792.Google Scholar
  72. Weill, M., C. Berticat, M. Raymond & C. Chevillon, 2000. Quantitative PCR to estimate the number of amplified esterase genes in insecticide resistant mosquitoes. Analytic. Biochem. 285: 267–270.Google Scholar
  73. Weill, M., M. Marquine, A. Berthomieux, M.-P. Dubois, C. Bernard, C.L. Qiao & M. Raymond, 2001. The diversity of amplified esterase gene in Chinese Culex pipiens mosquitoes J. Am. Nosq. Cont. Assoc. 17: (in press).Google Scholar
  74. Xu, J., F. Qu & W. Liu, 1994. Diversity of amplified esterase B genes responsible for organophosphate resistance in Culex quinquefasciatus from China. J. Med. Coll. PLA 9: 20–23.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Michel Raymond
    • 1
  • Claire Berticat
    • 2
  • Mylène Weill
    • 2
  • Nicole Pasteur
    • 2
  • Christine Chevillon
    • 2
  1. 1.Institut des Sciences de l'Evolution, Laboratoire Génétique et Environnement (C.C. 065), UMR CNRS 5554Université de Montpellier IIMontpellierFrance
  2. 2.Institut des Sciences de l'Evolution, Laboratoire Génétique et Environnement (C.C. 065), UMR CNRS 5554Université de Montpellier IIMontpellierFrance

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