Comparative Genomics Suggests an Independent Origin of Cytoplasmic Incompatibility in
Terrestrial arthropods are commonly infected with maternally inherited bacterial symbionts that cause cytoplasmic incompatibility (CI). In CI, the outcome of crosses between symbiont-infected males and uninfected females is reproductive failure, increasing the relative fitness of infected females and leading to spread of the symbiont in the host population. CI symbionts have profound impacts on host genetic structure and ecology and may lead to speciation and the rapid evolution of sex determination systems. Cardinium hertigii, a member of the Bacteroidetes and symbiont of the parasitic wasp Encarsia pergandiella, is the only known bacterium other than the Alphaproteobacteria Wolbachia to cause CI. Here we report the genome sequence of Cardinium hertigii cEper1. Comparison with the genomes of CI–inducing Wolbachia pipientis strains wMel, wRi, and wPip provides a unique opportunity to pinpoint shared proteins mediating host cell interaction, including some candidate proteins for CI that have not previously been investigated. The genome of Cardinium lacks all major biosynthetic pathways but harbors a complete biotin biosynthesis pathway, suggesting a potential role for Cardinium in host nutrition. Cardinium lacks known protein secretion systems but encodes a putative phage-derived secretion system distantly related to the antifeeding prophage of the entomopathogen Serratia entomophila. Lastly, while Cardinium and Wolbachia genomes show only a functional overlap of proteins, they show no evidence of laterally transferred elements that would suggest common ancestry of CI in both lineages. Instead, comparative genomics suggests an independent evolution of CI in Cardinium and Wolbachia and provides a novel context for understanding the mechanistic basis of CI.
Vyšlo v časopise:
Comparative Genomics Suggests an Independent Origin of Cytoplasmic Incompatibility in. PLoS Genet 8(10): e32767. doi:10.1371/journal.pgen.1003012
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Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1003012
Souhrn
Terrestrial arthropods are commonly infected with maternally inherited bacterial symbionts that cause cytoplasmic incompatibility (CI). In CI, the outcome of crosses between symbiont-infected males and uninfected females is reproductive failure, increasing the relative fitness of infected females and leading to spread of the symbiont in the host population. CI symbionts have profound impacts on host genetic structure and ecology and may lead to speciation and the rapid evolution of sex determination systems. Cardinium hertigii, a member of the Bacteroidetes and symbiont of the parasitic wasp Encarsia pergandiella, is the only known bacterium other than the Alphaproteobacteria Wolbachia to cause CI. Here we report the genome sequence of Cardinium hertigii cEper1. Comparison with the genomes of CI–inducing Wolbachia pipientis strains wMel, wRi, and wPip provides a unique opportunity to pinpoint shared proteins mediating host cell interaction, including some candidate proteins for CI that have not previously been investigated. The genome of Cardinium lacks all major biosynthetic pathways but harbors a complete biotin biosynthesis pathway, suggesting a potential role for Cardinium in host nutrition. Cardinium lacks known protein secretion systems but encodes a putative phage-derived secretion system distantly related to the antifeeding prophage of the entomopathogen Serratia entomophila. Lastly, while Cardinium and Wolbachia genomes show only a functional overlap of proteins, they show no evidence of laterally transferred elements that would suggest common ancestry of CI in both lineages. Instead, comparative genomics suggests an independent evolution of CI in Cardinium and Wolbachia and provides a novel context for understanding the mechanistic basis of CI.
Zdroje
1. MoranNA, McCutcheonJP, NakabachiA (2008) Genomics and evolution of heritable bacterial symbionts. Annu Rev Genet 42: 165–190.
2. HedgesLM, BrownlieJC, O'NeillSL, JohnsonKN (2008) Wolbachia and virus protection in insects. Science 322: 702.
3. OliverKM, RussellJA, MoranNA, HunterMS (2003) Facultative bacterial symbionts in aphids confer resistance to parasitic wasps. Proc Natl Acad Sci U S A 100: 1803–1807.
4. NakabachiA, YamashitaA, TohH, IshikawaH, DunbarHE, et al. (2006) The 160-kilobase genome of the bacterial endosymbiont Carsonella. Science 314: 267.
5. WerrenJH, BaldoL, ClarkME (2008) Wolbachia: master manipulators of invertebrate biology. Nat Rev Microbiol 6: 741–751.
6. SerbusLR, Casper-LindleyC, LandmannF, SullivanW (2008) The genetics and cell biology of Wolbachia-host interactions. Annu Rev Genet 42: 683–707.
7. CordauxR, BouchonD, GreveP (2011) The impact of endosymbionts on the evolution of host sex-determination mechanisms. Trends Genet 27: 332–341.
8. TelschowA, FlorM, KobayashiY, HammersteinP, WerrenJH (2007) Wolbachia-induced unidirectional cytoplasmic incompatibility and speciation: mainland-island model. PLoS ONE 2: e701 doi:10.1371/journal.pone.0000701..
9. JigginsFM, HurstGDD, MajerusMEN (2000) Sex-ratio-distorting Wolbachia causes sex-role reversal in its butterfly host. Proceedings of the Royal Society B-Biological Sciences 267: 69–73.
10. ZabalouS, RieglerM, TheodorakopoulouM, StaufferC, SavakisC, et al. (2004) Wolbachia-induced cytoplasmic incompatibility as a means for insect pest population control. Proc Natl Acad Sci U S A 101: 15042–15045.
11. WalkerT, JohnsonPH, MoreiraLA, Iturbe-OrmaetxeI, FrentiuFD, et al. (2011) The wMel Wolbachia strain blocks dengue and invades caged Aedes aegypti populations. Nature 476: 450–453.
12. ZugR, HammersteinP (2012) Still a host of hosts for wolbachia: analysis of recent data suggests that 40% of terrestrial arthropod species are infected. PLoS ONE 7: e38544 doi:10.1371/journal.pone.0038544..
13. TaylorMJ, HoeraufA (1999) Wolbachia bacteria of filarial nematodes. Parasitol Today 15: 437–442.
14. WerrenJH (1997) Biology of Wolbachia. Annu Rev Entomol 42: 587–609.
15. LassyCW, KarrTL (1996) Cytological analysis of fertilization and early embryonic development in incompatible crosses of Drosophila simulans. Mech Dev 57: 47–58.
16. TramU, SullivanW (2002) Role of delayed nuclear envelope breakdown and mitosis in Wolbachia-induced cytoplasmic incompatibility. Science 296: 1124–1126.
17. GavotteL, HenriH, StouthamerR, CharifD, CharlatS, et al. (2007) A Survey of the bacteriophage WO in the endosymbiotic bacteria Wolbachia. Mol Biol Evol 24: 427–435.
18. SinkinsSP, WalkerT, LyndAR, StevenAR, MakepeaceBL, et al. (2005) Wolbachia variability and host effects on crossing type in Culex mosquitoes. Nature 436: 257–260.
19. PapafotiouG, OehlerS, SavakisC, BourtzisK (2011) Regulation of Wolbachia ankyrin domain encoding genes in Drosophila gonads. Res Microbiol 162: 764–772.
20. KlassonL, WalkerT, SebaihiaM, SandersMJ, QuailMA, et al. (2008) Genome evolution of Wolbachia strain wPip from the Culex pipiens group. Mol Biol Evol 25: 1877–1887.
21. KlassonL, WestbergJ, SapountzisP, NaslundK, LutnaesY, et al. (2009) The mosaic genome structure of the Wolbachia wRi strain infecting Drosophila simulans. Proc Natl Acad Sci U S A 106: 5725–5730.
22. WuM, SunLV, VamathevanJ, RieglerM, DeboyR, et al. (2004) Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements. PLoS Biol 2: e69 doi:10.1371/journal.pbio.0020069..
23. HunterMS, PerlmanSJ, KellySE (2003) A bacterial symbiont in the Bacteroidetes induces cytoplasmic incompatibility in the parasitoid wasp Encarsia pergandiella. Proc Biol Sci 270: 2185–2190.
24. DuronO, HurstGD, HornettEA, JoslingJA, EngelstadterJ (2008) High incidence of the maternally inherited bacterium Cardinium in spiders. Mol Ecol 17: 1427–1437.
25. DallaiR, MercatiD, GiustiF, GottardoM, CarapelliA (2011) A Cardinium-like symbiont in the proturan Acerella muscorum (Hexapoda). Tissue Cell 43: 151–156.
26. NakamuraY, KawaiS, YukuhiroF, ItoS, GotohT, et al. (2009) Prevalence of Cardinium bacteria in planthoppers and spider mites and taxonomic revision of “Candidatus Cardinium hertigii” based on detection of a new Cardinium group from biting midges. Applied and Environmental Microbiology 75: 6757–6763.
27. NoelGR, AtibalentjaN (2006) ‘Candidatus Paenicardinium endonii’, an endosymbiont of the plant-parasitic nematode Heterodera glycines (Nemata: Tylenchida), affiliated to the phylum Bacteroidetes. Int J Syst Evol Microbiol 56: 1697–1702.
28. HornM, HarzenetterMD, LinnerT, SchmidEN, MullerKD, et al. (2001) Members of the Cytophaga-Flavobacterium-Bacteroides phylum as intracellular bacteria of acanthamoebae: proposal of ‘Candidatus Amoebophilus asiaticus’. Environ Microbiol 3: 440–449.
29. McCutcheonJP, MoranNA (2011) Extreme genome reduction in symbiotic bacteria. Nat Rev Microbiol 10: 13–26.
30. MoyaA, PeretoJ, GilR, LatorreA (2008) Learning how to live together: genomic insights into prokaryote-animal symbioses. Nat Rev Genet 9: 218–229.
31. NewtonIL, BordensteinSR (2011) Correlations between bacterial ecology and mobile DNA. Curr Microbiol 62: 198–208.
32. WuD, DaughertySC, Van AkenSE, PaiGH, WatkinsKL, et al. (2006) Metabolic complementarity and genomics of the dual bacterial symbiosis of sharpshooters. PLoS Biol 4: e188 doi:10.1371/journal.pbio.0040188..
33. BaldridgeGD, BurkhardtNY, FelsheimRF, KurttiTJ, MunderlohUG (2008) Plasmids of the pRM/pRF family occur in diverse Rickettsia species. Appl Environ Microbiol 74: 645–652.
34. OgataH, RenestoP, AudicS, RobertC, BlancG, et al. (2005) The genome sequence of Rickettsia felis identifies the first putative conjugative plasmid in an obligate intracellular parasite. PLoS Biol 3: e248 doi:10.1371/journal.pbio.0030248..
35. GillespieJJ, JoardarV, WilliamsKP, DriscollT, HostetlerJB, et al. (2011) A Rickettsia genome overrun by mobile genetic elements provides insight into the acquisition of genes characteristic of obligate intracellular lifestyle. J Bacteriol 194: 376–394.
36. TatusovRL, GalperinMY, NataleDA, KooninEV (2000) The COG database: a tool for genome-scale analysis of protein functions and evolution. Nucleic Acids Res 28: 33–36.
37. Schmitz-EsserS, TischlerP, ArnoldR, MontanaroJ, WagnerM, et al. (2010) The genome of the amoeba symbiont “Candidatus Amoebophilus asiaticus” reveals common mechanisms for host cell interaction among amoeba-associated bacteria. J Bacteriol 192: 1045–1057.
38. SpaldingMD, PriggeST (2010) Lipoic acid metabolism in microbial pathogens. Microbiology and Molecular Biology Reviews 74: 200–228.
39. LipkeH, FraenkelG (1956) Insect nutrition. Annual Review of Entomology 1: 17–44.
40. AkmanL, YamashitaA, WatanabeH, OshimaK, ShibaT, et al. (2002) Genome sequence of the endocellular obligate symbiont of tsetse flies, Wigglesworthia glossinidia. Nat Genet 32: 402–407.
41. Dunning HotoppJC, LinM, MadupuR, CrabtreeJ, AngiuoliSV, et al. (2006) Comparative genomics of emerging human ehrlichiosis agents. PLoS Genet 2: e21 doi:10.1371/journal.pgen.0020021..
42. HosokawaT, KogaR, KikuchiY, MengXY, FukatsuT (2010) Wolbachia as a bacteriocyte-associated nutritional mutualist. Proc Natl Acad Sci U S A 107: 769–774.
43. PerlmanSJ, KellySE, HunterMS (2008) Population biology of cytoplasmic incompatibility: maintenance and spread of Cardinium symbionts in a parasitic wasp. Genetics 178: 1003–1011.
44. BrownlieJC, CassBN, RieglerM, WitsenburgJJ, Iturbe-OrmaetxeI, et al. (2009) Evidence for metabolic provisioning by a common invertebrate endosymbiont, Wolbachia pipientis, during periods of nutritional stress. PLoS Pathog 5: e1000368 doi:10.1371/journal.ppat.1000368..
45. HimlerAG, Adachi-HagimoriT, BergenJE, KozuchA, KellySE, et al. (2011) Rapid Spread of a Bacterial Symbiont in an Invasive Whitefly Is Driven by Fitness Benefits and Female Bias. Science 332: 254–256.
46. PrestonGM (2007) Metropolitan Microbes: Type III Secretion in Multihost Symbionts. Cell Host Microbe 2: 291–294.
47. CoombesBK (2009) Type III secretion systems in symbiotic adaptation of pathogenic and non-pathogenic bacteria. Trends in Microbiology 17: 89–94.
48. DaleC, MoranNA (2006) Molecular interactions between bacterial symbionts and their hosts. Cell 126: 453–465.
49. RancèsE, VoroninD, Tran-VanV, MavinguiP (2008) Genetic and functional characterization of the type IV secretion system in Wolbachia. J Bacteriol 190: 5020–5030.
50. PenzT, HornM, Schmitz-EsserS (2011) The genome of the amoeba symbiont “Candidatus Amoebophilus asiaticus” encodes an afp-like prophage possibly used for protein secretion. Virulence 1: 541–545.
51. HurstMR, BeardSS, JacksonTA, JonesSM (2007) Isolation and characterization of the Serratia entomophila antifeeding prophage. FEMS Microbiol Lett 270: 42–48.
52. PerssonOP, PinhassiJ, RiemannL, MarklundBI, RhenM, et al. (2009) High abundance of virulence gene homologues in marine bacteria. Environ Microbiol 11: 1348–1357.
53. FurusawaG, YoshikawaT, TakanoY, MiseK, FurusawaI, et al. (2005) Characterization of cytoplasmic fibril structures found in gliding cells of Saprospira sp. Can J Microbiol 51: 875–880.
54. BigliardiE, SacchiL, GenchiM, AlmaA, PajoroM, et al. (2006) Ultrastructure of a novel Cardinium sp. symbiont in Scaphoideus titanus (Hemiptera: Cicadellidae). Tissue Cell 38: 257–261.
55. Zchori-FeinE, GottliebY, KellySE, BrownJK, WilsonJM, et al. (2001) A newly discovered bacterium associated with parthenogenesis and a change in host selection behavior in parasitoid wasps. Proc Natl Acad Sci U S A 98: 12555–12560.
56. Zchori-FeinE, PerlmanSJ, KellySE, KatzirN, HunterMS (2004) Characterization of a ‘Bacteroidetes’ symbiont in Encarsia wasps (Hymenoptera: Aphelinidae): proposal of ‘Candidatus Cardinium hertigii’. Int J Syst Evol Microbiol 54: 961–968.
57. BonemannG, PietrosiukA, MogkA (2010) Tubules and donuts: a type VI secretion story. Mol Microbiol 76: 815–821.
58. LeimanPG, BaslerM, RamagopalUA, BonannoJB, SauderJM, et al. (2009) Type VI secretion apparatus and phage tail-associated protein complexes share a common evolutionary origin. Proc Natl Acad Sci U S A 106: 4154–4159.
59. JehlMA, ArnoldR, RatteiT (2011) Effective - a database of predicted secreted bacterial proteins. Nucleic Acids Res 39: D591–595.
60. BlatchGL, LassleM (1999) The tetratricopeptide repeat: a structural motif mediating protein-protein interactions. Bioessays 21: 932–939.
61. SchreiberA, StengelF, ZhangZ, EnchevRI, KongEH, et al. (2011) Structural basis for the subunit assembly of the anaphase-promoting complex. Nature 470: 227–232.
62. FosterJ, GanatraM, KamalI, WareJ, MakarovaK, et al. (2005) The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode. PLoS Biol 3: e121 doi:10.1371/journal.pbio.0030121..
63. LiJ, MahajanA, TsaiMD (2006) Ankyrin repeat: a unique motif mediating protein-protein interactions. Biochemistry 45: 15168–15178.
64. AxtonJM, ShamanskiFL, YoungLM, HendersonDS, BoydJB, et al. (1994) The inhibitor of DNA replication encoded by the Drosophila gene plutonium is a small, ankyrin repeat protein. EMBO J 13: 462–470.
65. PanX, LuhrmannA, SatohA, Laskowski-ArceMA, RoyCR (2008) Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science 320: 1651–1654.
66. VothDE (2011) ThANKs for the repeat: Intracellular pathogens exploit a common eukaryotic domain. Cell Logist 1: 128–132.
67. Iturbe-OrmaetxeI, BurkeGR, RieglerM, O'NeillSL (2005) Distribution, expression, and motif variability of ankyrin domain genes in Wolbachia pipientis. J Bacteriol 187: 5136–5145.
68. DuronO, BoureuxA, EchaubardP, BerthomieuA, BerticatC, et al. (2007) Variability and expression of ankyrin domain genes in Wolbachia variants infecting the mosquito Culex pipiens. J Bacteriol 189: 4442–4448.
69. PekJW, KaiT (2011) DEAD-box RNA helicase Belle/DDX3 and the RNA interference pathway promote mitotic chromosome segregation. Proc Natl Acad Sci U S A 108: 12007–12012.
70. RytkonenA, HoldenDW (2007) Bacterial interference of ubiquitination and deubiquitination. Cell Host Microbe 1: 13–22.
71. WilkesTE, DarbyAC, ChoiJH, ColbourneJK, WerrenJH, et al. (2010) The draft genome sequence of Arsenophonus nasoniae, son-killer bacterium of Nasonia vitripennis, reveals genes associated with virulence and symbiosis. Insect Mol Biol 19 Suppl 1: 59–73.
72. HuM, LiP, LiM, LiW, YaoT, et al. (2002) Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with Ubiquitin Aldehyde. Cell 111: 1041–1054.
73. NijmanSM, Luna-VargasMP, VeldsA, BrummelkampTR, DiracAM, et al. (2005) A genomic and functional inventory of deubiquitinating enzymes. Cell 123: 773–786.
74. StifflerLA, JiJY, TrautmannS, TrustyC, SchubigerG (1999) Cyclin A and B functions in the early Drosophila embryo. Development 126: 5505–5513.
75. HaglundCM, ChoeJE, SkauCT, KovarDR, WelchMD (2010) Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility. Nat Cell Biol 12: 1057–1063.
76. KentBN, FunkhouserLJ, SetiaS, BordensteinSR (2011) Evolutionary genomics of a temperate bacteriophage in an obligate intracellular bacteria (Wolbachia). PLoS ONE 6: e24984 doi:10.1371/journal.pone.0024984..
77. RasmussenM, JacobssonM, BjorckL (2003) Genome-based identification and analysis of collagen-related structural motifs in bacterial and viral proteins. J Biol Chem 278: 32313–32316.
78. PatersonGK, NieminenL, JefferiesJM, MitchellTJ (2008) PclA, a pneumococcal collagen-like protein with selected strain distribution, contributes to adherence and invasion of host cells. FEMS Microbiol Lett 285: 170–176.
79. Schmitz-EsserS, PenzT, SpangA, HornM (2011) A bacterial genome in transition - an exceptional enrichment of IS elements but lack of evidence for recent transposition in the symbiont Amoebophilus asiaticus. BMC Evol Biol 11: 270.
80. SiguierP, FileeJ, ChandlerM (2006) Insertion sequences in prokaryotic genomes. Curr Opin Microbiol 9: 526–531.
81. TouchonM, RochaEP (2007) Causes of insertion sequences abundance in prokaryotic genomes. Mol Biol Evol 24: 969–981.
82. NakayamaK, YamashitaA, KurokawaK, MorimotoT, OgawaM, et al. (2008) The Whole-genome sequencing of the obligate intracellular bacterium Orientia tsutsugamushi revealed massive gene amplification during reductive genome evolution. DNA Res 15: 185–199.
83. ChoNH, KimHR, LeeJH, KimSY, KimJ, et al. (2007) The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host-cell interaction genes. Proc Natl Acad Sci U S A 104: 7981–7986.
84. BordensteinSR, ReznikoffWS (2005) Mobile DNA in obligate intracellular bacteria. Nat Rev Microbiol 3: 688–699.
85. GeorgiadesK, MerhejV, El KarkouriK, RaoultD, PontarottiP (2011) Gene gain and loss events in Rickettsia and Orientia species. Biol Direct 6: 6.
86. GimenezG, BertelliC, MolinerC, RobertC, RaoultD, et al. (2011) Insight into cross-talk between intra-amoebal pathogens. BMC Genomics 12.
87. MolmeretM, HornM, WagnerM, SanticM, Abu KwaikY (2005) Amoebae as training grounds for intracellular bacterial pathogens. Appl Environ Microbiol 71: 20–28.
88. ToftC, AnderssonSG (2010) Evolutionary microbial genomics: insights into bacterial host adaptation. Nat Rev Genet 11: 465–475.
89. WhiteJA, KellySE, CockburnSN, PerlmanSJ, HunterMS (2011) Endosymbiont costs and benefits in a parasitoid infected with both Wolbachia and Cardinium. Heredity 106: 585–591.
90. SkaljacM, ZanicK, BanSG, KontsedalovS, GhanimM (2010) Co-infection and localization of secondary symbionts in two whitefly species. BMC Microbiol 10: 142.
91. SirvioA, PamiloP (2010) Multiple endosymbionts in populations of the ant Formica cinerea. BMC Evol Biol 10: 335.
92. BraigHR, ZhouWG, DobsonSL, O'NeillSL (1998) Cloning and characterization of a gene encoding the major surface protein of the bacterial endosymbiont Wolbachia pipientis. J Bacteriol 180: 2373–2378.
93. ZhouJ, BrunsMA, TiedjeJM (1996) DNA recovery from soils of diverse composition. Appl Environ Microbiol 62: 316–322.
94. VallenetD, LabarreL, RouyZ, BarbeV, BocsS, et al. (2006) MaGe: a microbial genome annotation system supported by synteny results. Nucleic Acids Res 34: 53–65.
95. StothardP, WishartDS (2005) Circular genome visualization and exploration using CGView. Bioinformatics 21: 537–539.
96. KanehisaM, ArakiM, GotoS, HattoriM, HirakawaM, et al. (2008) KEGG for linking genomes to life and the environment. Nucleic Acids Res 36: D480–484.
97. SaierMHJr, YenMR, NotoK, TamangDG, ElkanC (2009) The transporter classification database: recent advances. Nucleic Acids Res 37: D274–278.
98. FinnRD, TateJ, MistryJ, CoggillPC, SammutSJ, et al. (2008) The Pfam protein families database. Nucleic Acids Res 36: D281–288.
99. LetunicI, DoerksT, BorkP (2009) SMART 6: recent updates and new developments. Nucleic Acids Res 37: D229–232.
100. KatohK, TohH (2008) Recent developments in the MAFFT multiple sequence alignment program. Brief Bioinform 9: 286–298.
101. EdgarRC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 1792–1797.
102. KumarS, NeiM, DudleyJ, TamuraK (2008) MEGA: a biologist-centric software for evolutionary analysis of DNA and protein sequences. Brief Bioinform 9: 299–306.
103. BaslerM, PilhoferM, HendersonGP, JensenGJ, MekalanosJJ (2012) Type VI secretion requires a dynamic contractile phage tail-like structure. Nature 483: 182–186.
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