The Three Faces of Riboviral Spontaneous Mutation: Spectrum, Mode of Genome Replication, and Mutation Rate
Riboviruses (RNA viruses without DNA replication intermediates) are the most abundant pathogens infecting animals and plants. Only a few riboviral infections can be controlled with antiviral drugs, mainly because of the rapid appearance of resistance mutations. Little reliable information is available concerning i) kinds and relative frequencies of mutations (the mutational spectrum), ii) mode of genome replication and mutation accumulation, and iii) rates of spontaneous mutation. To illuminate these issues, we developed a model in vivo system based on phage Qß infecting its natural host, Escherichia coli. The Qß RT gene encoding the Read-Through protein was used as a mutation reporter. To reduce uncertainties in mutation frequencies due to selection, the experimental Qß populations were established after a single cycle of infection and selection against RT − mutants during phage growth was ameliorated by plasmid-based RT complementation in trans. The dynamics of Qß genome replication were confirmed to reflect the linear process of iterative copying (the stamping-machine mode). A total of 32 RT mutants were detected among 7,517 Qß isolates. Sequencing analysis of 45 RT mutations revealed a spectrum dominated by 39 transitions, plus 4 transversions and 2 indels. A clear template•primer mismatch bias was observed: A•C>C•A>U•G>G•U> transversion mismatches. The average mutation rate per base replication was ≈9.1×10−6 for base substitutions and ≈2.3×10−7 for indels. The estimated mutation rate per genome replication, μg, was ≈0.04 (or, per phage generation, ≈0.08), although secondary RT mutations arose during the growth of some RT mutants at a rate about 7-fold higher, signaling the possible impact of transitory bouts of hypermutation. These results are contrasted with those previously reported for other riboviruses to depict the current state of the art in riboviral mutagenesis.
Vyšlo v časopise:
The Three Faces of Riboviral Spontaneous Mutation: Spectrum, Mode of Genome Replication, and Mutation Rate. PLoS Genet 8(7): e32767. doi:10.1371/journal.pgen.1002832
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002832
Souhrn
Riboviruses (RNA viruses without DNA replication intermediates) are the most abundant pathogens infecting animals and plants. Only a few riboviral infections can be controlled with antiviral drugs, mainly because of the rapid appearance of resistance mutations. Little reliable information is available concerning i) kinds and relative frequencies of mutations (the mutational spectrum), ii) mode of genome replication and mutation accumulation, and iii) rates of spontaneous mutation. To illuminate these issues, we developed a model in vivo system based on phage Qß infecting its natural host, Escherichia coli. The Qß RT gene encoding the Read-Through protein was used as a mutation reporter. To reduce uncertainties in mutation frequencies due to selection, the experimental Qß populations were established after a single cycle of infection and selection against RT − mutants during phage growth was ameliorated by plasmid-based RT complementation in trans. The dynamics of Qß genome replication were confirmed to reflect the linear process of iterative copying (the stamping-machine mode). A total of 32 RT mutants were detected among 7,517 Qß isolates. Sequencing analysis of 45 RT mutations revealed a spectrum dominated by 39 transitions, plus 4 transversions and 2 indels. A clear template•primer mismatch bias was observed: A•C>C•A>U•G>G•U> transversion mismatches. The average mutation rate per base replication was ≈9.1×10−6 for base substitutions and ≈2.3×10−7 for indels. The estimated mutation rate per genome replication, μg, was ≈0.04 (or, per phage generation, ≈0.08), although secondary RT mutations arose during the growth of some RT mutants at a rate about 7-fold higher, signaling the possible impact of transitory bouts of hypermutation. These results are contrasted with those previously reported for other riboviruses to depict the current state of the art in riboviral mutagenesis.
Zdroje
1. HolmesEC 2009 The evolution and emergence of RNA viruses Oxford University Press 254
2. DomingoE 2010 Mechanisms of viral emergence. Vet Res 41 38
3. DomingoEHollandJJ 1997 RNA virus mutations and fitness for survival. Annu Rev Microbiol 51 151 178
4. DrakeJWHollandJJ 1999 Mutation rates among RNA viruses. Proc Natl Acad Sci U S A 96 13910 13913
5. SanjuánRNebotMRChiricoNManskyLMBelshawR 2010 Viral mutation rates. J Virol 84 9733 9748
6. BurchCLGuyaderSSamarovDShenH 2007 Experimental estimate of the abundance and effects of nearly neutral mutations in the RNA virus φ6. Genetics 176 467 476
7. DrakeJW 1993 Rates of spontaneous mutation among RNA viruses. Proc Natl Acad Sci U S A 90 4171 4175
8. ChaoLRangCUWongLE 2002 Distribution of spontaneous mutants and the inferences about the replication mode of the RNA bacteriophage φ6. J Virol 76 3276 3281
9. SardanyésJMartínezFDaròsJ-AElenaSF 2011 Dynamics of a plant RNA virus intracellular accumulation: stamping machine vs. geometric replication. Genetics 188 637 646
10. MalpicaJMFraileAMorenoIObiesCIDrakeJW 2002 The rate and character of spontaneous mutation in an RNA virus. Genetics 162 1505 1511
11. TromasNElenaSF 2010 The rate and spectrum of spontaneous mutations in a plant RNA virus. Genetics 185 983 989
12. DasATBerkhoutB 2010 HIV-1 evolution: frustrating therapies, but disclosing molecular mechanisms. Phil Trans R Soc B 365 1965 1973
13. AndersonJPDaifukuRLoebLA 2004 Viral error catastrophe by mutagenic nucleosides. Ann Rev Microbiol 58 183 205
14. WeissmannC 1974 The making of a phage. FEBS Lett 40 S10 S18
15. WoodyMACliverDO 1995 Effects of temperature and host cell growth phase on replication of F-specific RNA coliphage Qß. Appl Environ Microbiol 61 1520 1526
16. WoodyMACliverDO 1997 Replication of coliphage Qß as affected by host cell number, nutrition, competition from insusceptible cells and non-FRNA coliphages. J Appl Microbiol 82 431 440
17. TsukadaKOkazakiMKitaHInokuchiYUrabeI 2009 Quantitative analysis of the bacteriophage Qß infection cycle. Biochim Biophys Acta 1790 65 70
18. GarwesDSilleroAOchoaS 1969 Virus-specific proteins in Escherichia coli infected with phage Qß. Biochim Biophys Acta 186 166 172
19. RadloffRJKaesbergP 1973 Electrophoretic and other properties of bacteriophage Qß: the effect of a variable number of Read-Through proteins. J Virol 11 116 128
20. BlumenthalTCarmichaelGG 1979 RNA replication: function and structure of Qß-replicase. Ann Rev Biochem 48 525 548
21. EigenMBiebricherCKGebinogaMGardinerWC 1991 The hypercycle. Coupling of RNA and protein biosynthesis in the infection cycle of an RNA bacteriophage. Biochemistry 30 11005 11018
22. HoriuchiKMatsuhashiS 1970 Three cistrons in bacteriophage Qß. Virology 42 49 60
23. VollenweiderHJKollerTWeberHWeissmannC 1976 Physical mapping of Qß replicase binding sites on Qß RNA. J Mol Biol 101 367 377
24. EdlindTDBasselAR 1977 Secondary structure of RNA from bacteriophages f2, Qß and PP7. J Virol 24 135 141
25. TakamatsuHIsoK 1982 Chemical evidence for the capsomeric structure of phage Qß. Nature 298 819 824
26. SchuppliDBarreraIWeberH 1994 Identification of recognition elements on bacteriophage Qß minus strand RNA that are essential for template activity with Qß replicase. J Mol Biol 243 811 815
27. GolmohammadiRFridborgKBunduleMValegårdKLiljasL 1996 The crystal structure of bacteriophage Qß at 3.5 Å resolution. Structure 4 543 554
28. BeekwilderMJNieuwenhuizenRvan DuinJ 1995 Secondary structure model for the last two domains of single-stranded RNA phage Qß. J Mol Biol 247 903 917
29. BeekwilderJNieuwenhuizenRPootRvan DuinJ 1996 Secondary structure model for the first three domains of Qß RNA. J Mol Biol 256 8 19
30. InokuchiYKajitaniM 1997 Deletion analysis of Qß replicase. J Biol Chem 272 15339 15345
31. KidmoseRTVasilievNNChetverinABRom AndersenGKnudsenCR 2010 Structure of the Qß replicase, an RNA-dependent RNA polymerase consisting of viral and host proteins. Proc Natl Acad Sci U S A 107 10884 10889
32. TakeshitaDTomitaK 2010 Assembly of Qß viral RNA polymerase with host translational elongation factors EF-Tu and -Ts. Proc Natl Acad Sci U S A 107 15733 15738
33. HofstetterHMonsteinH-JWeissmannC 1974 The readthrough protein A1 is essential for the formation of viable Qß particles. Biochim Biophys Acta 374 238 251
34. Van DuinJTsarevaN 2006 Single-stranded RNA phages. CalendarR The bacteriophages. 2nd edition Oxford University Press 175 196
35. PrianoCAroraRButkeJMillsDR 1995 A complete plasmid-based complementation system for RNA coliphage Qß: three proteins of bacteriophages Qß (Group III) and SP (Group IV) can be interchanged. J Mol Biol 249 283 297
36. AroraRPrianoCJacobsonABMillsDR 1996 cis-Acting elements within an RNA coliphage genome: fold as you please, but fold you must!! J Mol Biol 258 433 446
37. StreisingerGOkadaYEmrichJNewtonJTsugitaA 1968 Frameshift mutations and the genetic code. Cold Spring Harbor Symp Quant Biol 31 77 84
38. BebenekKKunkelTA 2000 Streisinger revisited: DNA synthesis errors mediated by substrate misalignments. Cold Spring Harbor Symp Quant Biol 65 81 92
39. HallidayJAGlickmanBW 1991 Mechanisms of spontaneous mutation in DNA repair-proficient Escherichia coli. Mutat Res 250 55 71
40. DrakeJW 2012 Contrasting mutation rates from specific-locus and long-term mutation-accumulation procedures. G3 2 483 485
41. BebenekADressmanHKCarverGTNgSPetrovV 2001 Interacting fidelity defects in the replicative DNA polymerase of bacteriophage RB69. J Biol Chem 276 10387 10397
42. LuriaSE 1951 The frequency distribution of spontaneous bacteriophage mutants as evidence for the exponential rate of phage reproduction. Cold Spring Harbor Symp Quant Biol 16 463 470
43. RonenARahatA 1976 Mutagen specific and position effects on mutation in T4rII nonsense sites. Mut Res 34 21 34
44. BilleterMALibonatiMViñuelaEWeissmannC 1966 Replication of viral ribonucleic acid. X. Turnover of virus-specific double-stranded ribonucleic acid during replication of phage MS2 in Escherichia coli. J Biol Chem 241 4750 4757
45. ThébaudGChadoeufJMorelliMJMcCauleyJWHaydonDT 2010 The relationship between mutation frequency and replication strategy in positive-sense single-stranded RNA viruses. Proc R Soc B 277 809 817
46. DrakeJW 2009 Avoiding dangerous missense: thermophiles display especially low mutation rates. PLoS Genet 5 e1000520 doi:10.1371/journal.pgen.1000520
47. LuriaSEDelbrückM 1943 Mutations in bacteria from virus sensitivity to virus resistance. Genetics 28 491 511
48. WagnerJNohmiT 2000 Escherichia coli DNA polymerase IV mutator activity: genetic requirements and mutational specificity. J Bacteriol 182 4587 4595
49. SchultzGEJrCarverGTDrakeJW 2006 A role for replication repair in the genesis of templated mutations. J Mol Biol 358 963 973
50. LangGIMurrayAW 2008 Estimating the per-base-pair mutation rate in the yeast Saccharomyces cerevisiae. Genetics 1789 67 82
51. FraserJLANeillEDaveyS 2003 Fission yeast Uve1 and Apn2 function in distinct oxidative damage repair pathways in vivo. DNA Repair 2 1253 1267
52. PowdrillMHTchesnokovEPKozakRARussellRSMartinR 2011 Contribution of a mutational bias in hepatitis C virus replication to the genetic barrier in the development of drug resistance. Proc Natl Acad Sci U S A 108 20509 20513
53. DenhardtDTSilverRB 1966 An analysis of the clone size distribution of φX174 mutants and recombinants. Virology 30 10 19
54. RegoesRRCrottySAntiaRTanakaMM 2005 Optimal replication of poliovirus within cells. Am Nat 165 364 373
55. LingCMHungPPOverbyLR 1970 Independent assembly of Qß and MS2 phages in doubly infected Escherichia coli. Virology 40 920 929
56. DrakeJWBebenekAKisslingGEPeddadaS 2005 Clusters of mutations from transient hypermutability. Proc Natl Acad Sci U S A 102 12849 12854
57. DrakeJW 2007 Mutations in clusters and showers. Proc Natl Acad Sci U S A 104 8203 8204
58. SanjuánRMoyaAElenaSF 2004 The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus. Proc Natl Acad Sci U S A 101 8396 8401
59. GiererAMudryKW 1958 Production of mutants of tobacco mosaic virus by chemical alteration of its ribonucleic acid in vitro. Nature 182 1457 1458
60. HollandJJDomingoEde la TorreJCSteinhauerDA 1990 Mutation frequencies at defined single codon sites in vesicular stomatitis virus and poliovirus can be increased only slightly by chemical mutagenesis. J Virol 64 3960 3962
61. MillsDRPrianoCMerzPABinderowBD 1990 Qß RNA bacteriophage: mapping cis-acting elements within an RNA genome. J Virol 64 3872 3881
62. SambrookJRussellDW 2001 Molecular cloning: a laboratory manual. 3rd edition Cold Spring Harbor (New York) Cold Spring Harbor Laboratory Press 999
63. YamamotoKRAlbertsBMBezingerRLawhorneLTreiberG 1970 Rapid bacteriophage sedimentation in the presence of polyethylene glycol and its application to large-scale virus purification. Virology 40 734 744
64. SokalRRRohlfFJ 1995 Biometry. 3rd edition W.H. Freeman and Company 887
65. KozminSGPavlovYIDunnRLSchaaperRM 2000 Hypersensitivity of Escherichia coli Δ(uvrB-bio) mutants to 6-hydroxylaminopurine and other base analogs is due to a defect in molybdenum cofactor biosynthesis. J Bacteriol 182 3361 3367
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 7
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- Guidelines for Genome-Wide Association Studies
- The Role of Rice HEI10 in the Formation of Meiotic Crossovers
- Identification of Chromatin-Associated Regulators of MSL Complex Targeting in Dosage Compensation
- GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers