Specific interactions between host genotypes and pathogen genotypes (G×G interactions) are commonly observed in invertebrate systems. Such specificity challenges our current understanding of invertebrate defenses against pathogens because it contrasts the limited discriminatory power of known invertebrate immune responses. Lack of a mechanistic explanation, however, has questioned the nature of host factors underlying G×G interactions. In this study, we aimed to determine whether G×G interactions observed between dengue viruses and their Aedes aegypti vectors in nature can be mapped to discrete loci in the mosquito genome and to document their genetic architecture. We developed an innovative genetic mapping strategy to survey G×G interactions using outbred mosquito families that were experimentally exposed to genetically distinct isolates of two dengue virus serotypes derived from human patients. Genetic loci associated with vector competence indices were detected in multiple regions of the mosquito genome. Importantly, correlation between genotype and phenotype was virus isolate-specific at several of these loci, indicating G×G interactions. The relatively high percentage of phenotypic variation explained by the markers associated with G×G interactions (ranging from 7.8% to 16.5%) is consistent with large-effect host genetic factors. Our data demonstrate that G×G interactions between dengue viruses and mosquito vectors can be assigned to physical regions of the mosquito genome, some of which have a large effect on the phenotype. This finding establishes the existence of tangible host genetic factors underlying specific interactions between invertebrates and their pathogens in a natural system. Fine mapping of the uncovered genetic loci will elucidate the molecular mechanisms of mosquito-virus specificity.
Vyšlo v časopise: Genetic Mapping of Specific Interactions between Mosquitoes and Dengue Viruses. PLoS Genet 9(8): e32767. doi:10.1371/journal.pgen.1003621 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003621
1. Thompson JN (2005) The geographic mosaic of coevolution. Chicago: University of Chicago Press. 400 p.
2. WadeMJ (2007) The co-evolutionary genetics of ecological communities. Nat Rev Genet 8 : 185–195.
3. LambrechtsL, FellousS, KoellaJC (2006) Coevolutionary interactions between host and parasite genotypes. Trends Parasitol 22 : 12–16.
4. HeathKD (2009) Intergenomic epistasis and coevolutionary constraint in plants and rhizobia. Evolution 64 : 1446–1458.
5. LambrechtsL (2010) Dissecting the genetic architecture of host-pathogen specificity. PLoS Pathog 6: e1001019.
6. Schmid-HempelP, EbertD (2003) On the evolutionary ecology of specific immune defence. Trends Ecol Evol 18 : 27–32.
7. CariusHJ, LittleTJ, EbertD (2001) Genetic variation in a host-parasite association: potential for coevolution and frequency-dependent selection. Evolution 55 : 1136–1145.
8. de RoodeJC, AltizerS (2009) Host-parasite genetic interactions and virulence-transmission relationships in natural populations of Monarch butterflies. Evolution 64 : 502–514.
9. LambrechtsL, ChevillonC, AlbrightRG, ThaisomboonsukB, RichardsonJH, et al. (2009) Genetic specificity and potential for local adaptation between dengue viruses and mosquito vectors. BMC Evol Biol 9 : 160.
10. LuijckxP, Ben-AmiF, MoutonL, Du PasquierL, EbertD (2011) Cloning of the unculturable parasite Pasteuria ramosa and its Daphnia host reveals extreme genotype-genotype interactions. Ecol Lett 14 : 125–131.
11. SchulenburgH, EwbankJJ (2004) Diversity and specificity in the interaction between Caenorhabditis elegans and the pathogen Serratia marcescens. BMC Evol Biol 4 : 49.
12. WebsterJP, WoolhouseMEJ (1998) Selection and strain specificity of compatibility between snail intermediate hosts and their parasitic schistosomes. Evolution 52 : 1627–1634.
13. LittleTJ, HultmarkD, ReadAF (2005) Invertebrate immunity and the limits of mechanistic immunology. Nat Immunol 6 : 651–654.
14. Schmid-HempelP (2005) Natural insect host-parasite systems show immune priming and specificity: puzzles to be solved. Bioessays 27 : 1026–1034.
15. HautonC, SmithVJ (2007) Adaptive immunity in invertebrates: a straw house without a mechanistic foundation. Bioessays 29 : 1138–1146.
16. KochH, Schmid-HempelP (2012) Gut microbiota instead of host genotype drive the specificity in the interaction of a natural host-parasite system. Ecol Lett 15 : 1095–1103.
17. WilfertL, Schmid-HempelP (2008) The genetic architecture of susceptibility to parasites. BMC Evol Biol 8 : 187.
18. SimmonsCP, FarrarJJ, NguyenvV, WillsB (2012) Dengue. N Engl J Med 366 : 1423–1432.
19. KramerLD, EbelGD (2003) Dynamics of flavivirus infection in mosquitoes. Adv Virus Res 60 : 187–232.
20. BennettKE, OlsonKE, Munoz MdeL, Fernandez-SalasI, Farfan-AleJA, et al. (2002) Variation in vector competence for dengue 2 virus among 24 collections of Aedes aegypti from Mexico and the United States. Am J Trop Med Hyg 67 : 85–92.
21. GublerDJ, NalimS, TanR, SaipanH, Sulianti SarosoJ (1979) Variation in susceptibility to oral infection with dengue viruses among geographic strains of Aedes aegypti. Am J Trop Med Hyg 28 : 1045–1052.
22. MillerBR, MitchellCJ (1991) Genetic selection of a flavivirus-refractory strain of the yellow fever mosquito Aedes aegypti. Am J Trop Med Hyg 45 : 399–407.
23. BennettKE, FlickD, FlemingKH, JochimR, BeatyBJ, et al. (2005) Quantitative trait loci that control dengue-2 virus dissemination in the mosquito Aedes aegypti. Genetics 170 : 185–194.
24. BosioCF, FultonRE, SalasekML, BeatyBJ, BlackWC (2000) Quantitative trait loci that control vector competence for dengue-2 virus in the mosquito Aedes aegypti. Genetics 156 : 687–698.
25. Gomez-MachorroC, BennettKE, del Lourdes MunozM, BlackWC (2004) Quantitative trait loci affecting dengue midgut infection barriers in an advanced intercross line of Aedes aegypti. Insect Mol Biol 13 : 637–648.
26. HolmesEC, TwiddySS (2003) The origin, emergence and evolutionary genetics of dengue virus. Infect Genet Evol 3 : 19–28.
27. LambrechtsL (2011) Quantitative genetics of Aedes aegypti vector competence for dengue viruses: towards a new paradigm? Trends Parasitol 27 : 111–114.
28. NiareO, MarkianosK, VolzJ, OduolF, ToureA, et al. (2002) Genetic loci affecting resistance to human malaria parasites in a West African mosquito vector population. Science 298 : 213–216.
29. RiehleMM, MarkianosK, NiareO, XuJ, LiJ, et al. (2006) Natural malaria infection in Anopheles gambiae is regulated by a single genomic control region. Science 312 : 577–579.
30. SlateJ (2005) Quantitative trait locus mapping in natural populations: progress, caveats and future directions. Mol Ecol 14 : 363–379.
31. WilfertL, GadauJ, BaerB, Schmid-HempelP (2007) Natural variation in the genetic architecture of a host-parasite interaction in the bumblebee Bombus terrestris. Mol Ecol 16 : 1327–1339.
32. BlackWC, BennettKE, Gorrochotegui-EscalanteN, Barillas-MuryCV, Fernandez-SalasI, et al. (2002) Flavivirus susceptibility in Aedes aegypti. Arch Med Res 33 : 379–388.
33. LambrechtsL, FansiriT, PongsiriA, ThaisomboonsukB, KlungthongC, et al. (2012) Dengue-1 virus clade replacement in Thailand associated with enhanced mosquito transmission. J Virol 86 : 1853–1861.
34. HuangW, RichardsS, CarboneMA, ZhuD, AnholtRR, et al. (2012) Epistasis dominates the genetic architecture of Drosophila quantitative traits. Proc Natl Acad Sci U S A 109 : 15553–15559.
35. PhillipsPC (2008) Epistasis–the essential role of gene interactions in the structure and evolution of genetic systems. Nat Rev Genet 9 : 855–867.
36. Sanchez-VargasI, ScottJC, Poole-SmithBK, FranzAW, Barbosa-SolomieuV, et al. (2009) Dengue virus type 2 infections of Aedes aegypti are modulated by the mosquito's RNA interference pathway. PLoS Pathog 5: e1000299.
37. Souza-NetoJA, SimS, DimopoulosG (2009) An evolutionary conserved function of the JAK-STAT pathway in anti-dengue defense. Proc Natl Acad Sci U S A 106 : 17841–17846.
38. XiZ, RamirezJL, DimopoulosG (2008) The Aedes aegypti toll pathway controls dengue virus infection. PLoS Pathog 4: e1000098.
39. LambrechtsL, QuilleryE, NoelV, RichardsonJH, JarmanRG, et al. (2013) Specificity of resistance to dengue virus isolates is associated with genotypes of the mosquito antiviral gene Dicer-2. Proc Biol Sci 280 : 20122437.
40. YoonIK, GetisA, AldstadtJ, RothmanAL, TannitisupawongD, et al. (2012) Fine scale spatiotemporal clustering of dengue virus transmission in children and Aedes aegypti in rural Thai villages. PLoS Negl Trop Dis 6: e1730.
41. LambrechtsL, ScottTW (2009) Mode of transmission and the evolution of arbovirus virulence in mosquito vectors. Proc Biol Sci 276 : 1369–1378.
42. CookS, MoureauG, KitchenA, GouldEA, de LamballerieX, et al. (2012) Molecular evolution of the insect-specific flaviviruses. J Gen Virol 93 : 223–234.
43. FranzAW, Sanchez-VargasI, AdelmanZN, BlairCD, BeatyBJ, et al. (2006) Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegypti. Proc Natl Acad Sci U S A 103 : 4198–4203.
44. MathurG, Sanchez-VargasI, AlvarezD, OlsonKE, MarinottiO, et al. (2010) Transgene-mediated suppression of dengue viruses in the salivary glands of the yellow fever mosquito, Aedes aegypti. Insect Mol Biol 19 : 753–763.
45. CarlborgO, HaleyCS (2004) Epistasis: too often neglected in complex trait studies? Nat Rev Genet 5 : 618–625.
46. MooreJH (2003) The ubiquitous nature of epistasis in determining susceptibility to common human diseases. Hum Hered 56 : 73–82.
47. BensonAK, KellySA, LeggeR, MaF, LowSJ, et al. (2010) Individuality in gut microbiota composition is a complex polygenic trait shaped by multiple environmental and host genetic factors. Proc Natl Acad Sci U S A 107 : 18933–18938.
48. LundbergDS, LebeisSL, ParedesSH, YourstoneS, GehringJ, et al. (2012) Defining the core Arabidopsis thaliana root microbiome. Nature 488 : 86–90.
49. EndyTP, NisalakA, ChunsuttiwatS, LibratyDH, GreenS, et al. (2002) Spatial and temporal circulation of dengue virus serotypes: a prospective study of primary school children in Kamphaeng Phet, Thailand. Am J Epidemiol 156 : 52–59.
50. CraigGBJr (1967) Mosquitoes: female monogamy induced by male accessory gland substance. Science 156 : 1499–1501.
51. TamuraK, PetersonD, PetersonN, StecherG, NeiM, et al. (2011) MEGA5: Molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28 : 2731–2739.
52. ThomasSJ, NisalakA, AndersonKB, LibratyDH, KalayanaroojS, et al. (2009) Dengue plaque reduction neutralization test (PRNT) in primary and secondary dengue virus infections: How alterations in assay conditions impact performance. Am J Trop Med Hyg 81 : 825–833.
53. ChambersEW, MeeceJK, McGowanJA, LovinDD, HemmeRR, et al. (2007) Microsatellite isolation and linkage group identification in the yellow fever mosquito Aedes aegypti. J Hered 98 : 202–210.
54. LovinDD, WashingtonKO, deBruynB, HemmeRR, MoriA, et al. (2009) Genome-based polymorphic microsatellite development and validation in the mosquito Aedes aegypti and application to population genetics in Haiti. BMC Genomics 10 : 590.
55. NeneV, WortmanJR, LawsonD, HaasB, KodiraC, et al. (2007) Genome sequence of Aedes aegypti, a major arbovirus vector. Science 316 : 1718–1723.
56. SeversonDW, MeeceJK, LovinDD, SahaG, MorlaisI (2002) Linkage map organization of expressed sequence tags and sequence tagged sites in the mosquito, Aedes aegypti. Insect Mol Biol 11 : 371–378.
57. BensonG (1999) Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res 27 : 573–580.
58. Rozen S, Skaletsky HJ (2000) Primer3 on the WWW for general users and for biologist programmers. In: Krawetz S, Misener S, editors. Bioinformatics methods and protocols: methods in molecular biology. Totowa, NJ: Humana Press. pp. 365–386.
59. Hastie TJ, Pregibon D (1991) Chapter 6: Generalized linear models. In: Chambers JM, Hastie TJ, editors. Statistical models in S: Wadsworth & Brooks/Cole.
60. R Core Team (2012) R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria.
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
