Volume 71, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


The genome sequence, together with the recent development of molecular tools for genome-wide analysis, promises new insights into the biology of the malaria vector. These insights should help define the best possible breakdown point for interrupting transmission in the mosquito vector. A survey of the intraspecific nucleotide diversity in coding regions of three different mosquito strains showed an average of one single nucleotide polymorphism (SNP) every 125 coding base pairs. High levels of nucleotide polymorphism were observed in mosquito immune-related genes and pathogen recognition receptors harbored higher replacement substitutions. Genotyping at SNP loci in natural populations of from three malaria foci showed contrasting patterns. The distribution of mutation Y443H in the thioester-containing protein 3 (TEP3) gene suggested this mutational event has occurred under selective constraints. Our results show that SNP-based studies will be valuable in identifying the sequence variation associated with phenotypic traits shaping vector competence.


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  1. Gouagna LC, Mulder B, Noubissi E, Tchuinkam T, Verhave JP, Boudin C, 1998. The early sporogonic cycle of Plasmodium falciparum in laboratory-infected Anopheles gambiae: an estimation of parasite efficacy. Trop Med Int Health 3 : 21–28.
  2. Dimopoulos G, Muller HM, Levashina EA, Kafatos FC, 2001. Innate immune defense against malaria infection in the mosquito. Curr Opin Immunol 13 : 79–88.
  3. Barillas-Mury C, Wizel B, Han YS, 2000. Mosquito immune responses and malaria transmission: lessons from insect model systems and implications for vertebrate innate immunity and vaccine development. Insect Biochem Mol Biol 30 : 429–442.
  4. Dimopoulos G, Christophides GK, Meister S, Schultz J, White KP, Barillas-Mury C, Kafatos FC, 2002. Genome expression analysis of Anopheles gambiae: responses to injury, bacterial challenge, and malaria infection. Proc Natl Acad Sci USA 99 : 8814–8819.
  5. Ito J, Ghosh A, Moreira LA, Wimmer EA, Jacobs-Lorena M, 2002. Transgenic anopheline mosquitoes impaired in transmission of a malaria parasite. Nature 417 : 452–455.
  6. Morlais I, Severson DW, 2001. Identification of a polymorphic mucin-like gene expressed in the midgut of the mosquito, Aedes aegypti, using an integrated bulked segregant and differential display analysis. Genetics 158 : 1125–1136.
  7. Christophides GK, Zdobnov E, Barillas-Mury C, Birney E, Blandin S, Blass C, Brey PT, Collins FH, Danielli A, Dimopoulos G, Hetru C, Hoa NT, Hoffmann JA, Kanzok SM, Letunic I, Levashina EA, Loukeris TG, Lycett G, Meister S, Michel K, Moita LF, Muller HM, Osta MA, Paskewitz SM, Reichhart JM, Rzhetsky A, Troxler L, Vernick KD, Vlachou D, Volz J, von Mering C, Xu J, Zheng L, Bork P, Kafatos FC, 2002. Immunity-related genes and gene families in Anopheles gambiae. Science 298 : 159–165.
  8. Catteruccia F, Nolan T, Loukeris TG, Blass C, Savakis C, Kafatos FC, Crisanti A, 2000. Stable germline transformation of the malaria mosquito Anopheles stephensi. Nature 405 : 959–962.
  9. Grossman GL, Rafferty CS, Clayton JR, Stevens TK, Mukabayire O, Benedict MQ, 2001. Germline transformation of the malaria vector, Anopheles gambiae, with the piggyBac transposable element. Insect Mol Biol 10 : 597–604.
  10. Syvanen AC, 2001. Accessing genetic variation: genotyping single nucleotide polymorphisms. Nat Rev Genet 2 : 930–942.
  11. Black WC IV, Baer CF, Antolin MF, DuTeau NM, 2001. Population genomics: genome-wide sampling of insect populations. Annu Rev Entomol 46 : 441–469.
  12. Berger J, Suzuki T, Senti KA, Stubbs J, Schaffner G, Dickson BJ, 2001. Genetic mapping with SNP markers in Drosophila. Nat Genet 29 : 475–481.
  13. Botstein D, Risch N, 2003. Discovering genotypes underlying human phenotypes: past successes for Mendelian disease, future approaches for complex disease. Nat Genet 33 (Suppl): 228–237.
  14. Holt RA, Subramanian GM, Halpern A, Sutton GG, Charlab R, Nusskern DR, Wincker P, Clark AG, Ribeiro JM, Wides R, Salzberg SL, Loftus B, Yandell M, Majoros WH, Rusch DB, Lai Z, Kraft CL, Abril JF, Anthouard V, Arensburger P, Atkinson PW, Baden H, de Berardinis V, Baldwin D, Benes V, Biedler J, Blass C, Bolanos R, Boscus D, Barnstead M, Cai S, Center A, Chatuverdi K, Christophides GK, Chrystal MA, Clamp M, Cravchik A, Curwen V, Dana A, Delcher A, Dew I, Evans CA, Flanigan M, Grundschober-Freimoser A, Friedli L, Gu Z, Guan P, Guigo R, Hillenmeyer ME, Hladun SL, Hogan JR, Hong YS, Hoover J, Jaillon O, Ke Z, Kodira C, Kokoza E, Koutsos A, Letunic I, Levitsky A, Liang Y, Lin JJ, Lobo NF, Lopez JR, Malek JA, McIntosh TC, Meister S, Miller J, Mobarry C, Mongin E, Murphy SD, O’Brochta DA, Pfannkoch C, Qi R, Regier MA, Remington K, Shao H, Sharakhova MV, Sitter CD, Shetty J, Smith TJ, Strong R, Sun J, Thomasova D, Ton LQ, Topalis P, Tu Z, Unger MF, Walenz B, Wang A, Wang J, Wang M, Wang X, Woodford KJ, Wortman JR, Wu M, Yao A, Zdobnov EM, Zhang H, Zhao Q, Zhao S, Zhu SC, Zhimulev I, Coluzzi M, della Torre A, Roth CW, Louis C, Kalush F, Mural RJ, Myers EW, Adams MD, Smith HO, Broder S, Gardner MJ, Fraser CM, Birney E, Bork P, Brey PT, Venter JC, Weissenbach J, Kafatos FC, Collins FH, Hoffman SL, 2002. The genome sequence of the malaria mosquito Anopheles gambiae. Science 298 : 129–149.
  15. della Torre A, Fanello C, Akogbeto M, Dossouyovo J, Favia G, Petrarca V, Coluzzi M, 2001. Molecular evidence of incipient speciation within Anopheles gambiae s.s. in West Africa. Insect Mol Biol 10 : 9–18.
  16. Tchuinkam T, Mulder B, Dechering K, Stoffels H, Verhave JP, Cot M, Carnevale P, Meuwissen JH, Robert V, 1993. Experimental infections of Anopheles gambiae with Plasmodium falciparum of naturally infected gametocyte carriers in Cameroon: factors influencing the infectivity to mosquitoes. Trop Med Parasitol 44 : 271–276.
  17. Collins FH, Sakai RK, Vernick KD, Paskewitz S, Seeley DC, Miller LH, Collins WE, Campbell CC, Gwadz RW, 1986. Genetic selection of a Plasmodium–refractory strain of the malaria vector Anopheles gambiae. Science 234 : 607–610.
  18. Zheng L, Cornel AJ, Wang R, Erfle H, Voss H, Ansorge W, Kafatos FC, Collins FH, 1997. Quantitative trait loci for refractoriness of Anopheles gambiae to Plasmodium cynomolgi B. Science 276 : 425–428.
  19. Cociancich SO, Park SS, Fidock DA, Shahabuddin M, 1999. Vesicular ATPase-overexpressing cells determine the distribution of malaria parasite oocysts on the midguts of mosquitoes. J Biol Chem 274 : 12650–12655.
  20. Rozen S, Skaletsky H, 2000. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132 : 365–386.
  21. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG, 1997. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25 : 4876–4882.
  22. Kumar S, Tamura K, Jakobsen IB, Nei M, 2001. MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17 : 1244–1245.
  23. Nei M, Kumar S, 2000. Molecular Evolution and Phylogenetics. New York: Oxford University Press.
  24. Fanello C, Santolamazza F, della Torre A, 2002. Simultaneous identification of species and molecular forms of the Anopheles gambiae complex by PCR-RFLP. Med Vet Entomol 16 : 461– 464.
  25. Wang HY, Tang H, Shen CK, Wu CI, 2003. Rapidly evolving genes in human. I. The glycophorins and their possible role in evading malaria parasites. Mol Biol Evol 20 : 1795–1804.
  26. Hughes AL, 1997. Rapid evolution of immunoglobulin superfamily C2 domains expressed in immune system cells. Mol Biol Evol 14 : 1–5.
  27. Aquadro CF, Bauer DuMont V, Reed FA, 2001. Genome-wide variation in the human and fruitfly: a comparison. Curr Opin Genet Dev 11 : 627–634.
  28. Morlais I, Severson DW, 2003. Intraspecific DNA variation in nuclear genes of the mosquito Aedes aegypti. Insect Mol Biol 12 : 631–639.
  29. della Torre A, Costantini C, Besansky NJ, Caccone A, Petrarca V, Powell JR, Coluzzi M, 2002. Speciation within Anopheles gambiae-the glass is half full. Science 298 : 115–117.
  30. Coluzzi M, Sabatini A, della Torre A, di Deco MA, Petrarca V, 2002. A polytene chromosome analysis of the Anopheles gambiae species complex. Science 298 : 1415–1418.
  31. Wondji C, Simard F, Fontenille D, 2002. Evidence for genetic differentiation between the molecular forms M and S within the Forest chromosomal form of Anopheles gambiae in an area of sympatry. Insect Mol Biol 11 : 11–19.
  32. Lercher MJ, Hurst LD, 2002. Human SNP variability and mutation rate are higher in regions of high recombination. Trends Genet 18 : 337–340.
  33. Volkman SK, Hartl DL, Wirth DF, Nielsen KM, Choi M, Batalov S, Zhou Y, Plouffe D, Le Roch KG, Abagyan R, Winzeler EA, 2002. Excess polymorphisms in genes for membrane proteins in Plasmodium falciparum. Science 298 : 216–218.
  34. Schlenke TA, Begun DJ, 2003. Natural selection drives Drosophila immune system evolution. Genetics 164 : 1471–1480.
  35. Schmid KJ, Tautz D, 1997. A screen for fast evolving genes from Drosophila. Proc Natl Acad Sci USA 94 : 9746–9750.
  36. Takken W, Eling W, Hooghof J, Dekker T, Hunt R, Coetzee M, 1999. Susceptibility of Anopheles quadriannulatus Theobald (Diptera: Culicidae) to Plasmodium falciparum. Trans R Soc Trop Med Hyg 93 : 578–580.
  37. Zdobnov EM, von Mering C, Letunic I, Torrents D, Suyama M, Copley RR, Christophides GK, Thomasova D, Holt RA, Subramanian GM, Mueller HM, Dimopoulos G, Law JH, Wells MA, Birney E, Charlab R, Halpern AL, Kokoza E, Kraft CL, Lai Z, Lewis S, Louis C, Barillas-Mury C, Nusskern D, Rubin GM, Salzberg SL, Sutton GG, Topalis P, Wides R, Wincker P, Yandell M, Collins FH, Ribeiro J, Gelbart WM, Kafatos FC, Bork P, 2002. Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster. Science 298 : 149–159.
  38. Schmid KJ, Nigro L, Aquadro CF, Tautz D, 1999. Large number of replacement polymorphisms in rapidly evolving genes of Drosophila. Implications for genome-wide surveys of DNA polymorphism. Genetics 153 : 1717–1729.
  39. Gentile G, Slotman M, Ketmaier V, Powell JR, Caccone A, 2001. Attempts to molecularly distinguish cryptic taxa in Anopheles gambiae s.s. Insect Mol Biol 10 : 25–32.
  40. Diabate A, Baldet T, Chandre C, Dabire KR, Kengne P, Guiguemde TR, Simard F, Guillet P, Hemingway J, Hougard JM, 2003. KDR mutation, a genetic marker to assess events of introgression between the molecular M and S forms of Anopheles gambiae (Diptera: Culicidae) in the tropical savannah area of west Africa. J Med Entomol 40 : 195–198.
  41. Blandin S, Levashina EA, 2004. Thioester-containing proteins and insect immunity. Mol Immunol 40 : 903–908.
  42. Martinez-Torres D, Chandre F, Williamson MS, Darriet F, Berge JB, Devonshire AL, Guillet P, Pasteur N, Pauron D, 1998. Molecular characterization of pyrethroid knockdown resistance (kdr) in the major malaria vector Anopheles gambiae s.s. Insect Mol Biol 7 : 179–184.
  43. Weill M, Lutfalla G, Mogensen K, Chandre F, Berthomieu A, Berticat C, Pasteur N, Philips A, Fort P, Raymond M, 2003. Comparative genomics: insecticide resistance in mosquito vectors. Nature 423 : 136–137.

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  • Received : 07 Apr 2004
  • Accepted : 29 Jun 2004

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