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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 May 1;90(9):4171–4175. doi: 10.1073/pnas.90.9.4171

Rates of spontaneous mutation among RNA viruses.

J W Drake 1
PMCID: PMC46468  PMID: 8387212

Abstract

Simple methods are presented to estimate rates of spontaneous mutation from mutant frequencies and population parameters in RNA viruses. Published mutant frequencies yield a wide range of mutation rates per genome per replication, mainly because mutational targets have usually been small and, thus, poor samples of the mutability of the average base. Nevertheless, there is a clear central tendency for lytic RNA viruses (bacteriophage Q beta, poliomyelitis, vesicular stomatitis, and influenza A) to display rates of spontaneous mutation of approximately 1 per genome per replication. This rate is some 300-fold higher than previously reported for DNA-based microbes. Lytic RNA viruses thus mutate at a rate close to the maximum value compatible with viability. Retroviruses (spleen necrosis, murine leukemia, Rous sarcoma), however, mutate at an average rate about an order of magnitude lower than lytic RNA viruses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Batschelet E., Domingo E., Weissmann C. The proportion of revertant and mutant phage in a growing population, as a function of mutation and growth rate. Gene. 1976;1(1):27–32. doi: 10.1016/0378-1119(76)90004-4. [DOI] [PubMed] [Google Scholar]
  2. Benzer S. FINE STRUCTURE OF A GENETIC REGION IN BACTERIOPHAGE. Proc Natl Acad Sci U S A. 1955 Jun 15;41(6):344–354. doi: 10.1073/pnas.41.6.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chao L. Fitness of RNA virus decreased by Muller's ratchet. Nature. 1990 Nov 29;348(6300):454–455. doi: 10.1038/348454a0. [DOI] [PubMed] [Google Scholar]
  4. Domingo E., Flavell R. A., Weissmann C. In vitro site-directed mutagenesis: generation and properties of an infectious extracistronic mutant of bacteriophage Qbeta. Gene. 1976;1(1):3–25. doi: 10.1016/0378-1119(76)90003-2. [DOI] [PubMed] [Google Scholar]
  5. Dougherty J. P., Temin H. M. Determination of the rate of base-pair substitution and insertion mutations in retrovirus replication. J Virol. 1988 Aug;62(8):2817–2822. doi: 10.1128/jvi.62.8.2817-2822.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Drake J. W. A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7160–7164. doi: 10.1073/pnas.88.16.7160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eigen M., Schuster P. The hypercycle. A principle of natural self-organization. Part A: Emergence of the hypercycle. Naturwissenschaften. 1977 Nov;64(11):541–565. doi: 10.1007/BF00450633. [DOI] [PubMed] [Google Scholar]
  8. Etzerodt M., Mikkelsen T., Pedersen F. S., Kjeldgaard N. O., Jørgensen P. The nucleotide sequence of the Akv murine leukemia virus genome. Virology. 1984 Apr 15;134(1):196–207. doi: 10.1016/0042-6822(84)90285-x. [DOI] [PubMed] [Google Scholar]
  9. Herr W. Nucleotide sequence of AKV murine leukemia virus. J Virol. 1984 Feb;49(2):471–478. doi: 10.1128/jvi.49.2.471-478.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Holland J. J., Domingo E., de la Torre J. C., Steinhauer D. A. Mutation frequencies at defined single codon sites in vesicular stomatitis virus and poliovirus can be increased only slightly by chemical mutagenesis. J Virol. 1990 Aug;64(8):3960–3962. doi: 10.1128/jvi.64.8.3960-3962.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Holland J. J., de la Torre J. C., Steinhauer D. A., Clarke D., Duarte E., Domingo E. Virus mutation frequencies can be greatly underestimated by monoclonal antibody neutralization of virions. J Virol. 1989 Dec;63(12):5030–5036. doi: 10.1128/jvi.63.12.5030-5036.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holland J., Spindler K., Horodyski F., Grabau E., Nichol S., VandePol S. Rapid evolution of RNA genomes. Science. 1982 Mar 26;215(4540):1577–1585. doi: 10.1126/science.7041255. [DOI] [PubMed] [Google Scholar]
  13. Kitamura N., Semler B. L., Rothberg P. G., Larsen G. R., Adler C. J., Dorner A. J., Emini E. A., Hanecak R., Lee J. J., van der Werf S. Primary structure, gene organization and polypeptide expression of poliovirus RNA. Nature. 1981 Jun 18;291(5816):547–553. doi: 10.1038/291547a0. [DOI] [PubMed] [Google Scholar]
  14. Kuge S., Kawamura N., Nomoto A. Strong inclination toward transition mutation in nucleotide substitutions by poliovirus replicase. J Mol Biol. 1989 May 5;207(1):175–182. doi: 10.1016/0022-2836(89)90448-8. [DOI] [PubMed] [Google Scholar]
  15. LURIA S. E. The frequency distribution of spontaneous bacteriophage mutants as evidence for the exponential rate of phage reproduction. Cold Spring Harb Symp Quant Biol. 1951;16:463–470. doi: 10.1101/sqb.1951.016.01.033. [DOI] [PubMed] [Google Scholar]
  16. Leider J. M., Palese P., Smith F. I. Determination of the mutation rate of a retrovirus. J Virol. 1988 Sep;62(9):3084–3091. doi: 10.1128/jvi.62.9.3084-3091.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Luria S. E., Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. doi: 10.1093/genetics/28.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mills D. R., Priano C., Merz P. A., Binderow B. D. Q beta RNA bacteriophage: mapping cis-acting elements within an RNA genome. J Virol. 1990 Aug;64(8):3872–3881. doi: 10.1128/jvi.64.8.3872-3881.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Monk R. J., Malik F. G., Stokesberry D., Evans L. H. Direct determination of the point mutation rate of a murine retrovirus. J Virol. 1992 Jun;66(6):3683–3689. doi: 10.1128/jvi.66.6.3683-3689.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Morrison A., Johnson A. L., Johnston L. H., Sugino A. Pathway correcting DNA replication errors in Saccharomyces cerevisiae. EMBO J. 1993 Apr;12(4):1467–1473. doi: 10.1002/j.1460-2075.1993.tb05790.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Parvin J. D., Moscona A., Pan W. T., Leider J. M., Palese P. Measurement of the mutation rates of animal viruses: influenza A virus and poliovirus type 1. J Virol. 1986 Aug;59(2):377–383. doi: 10.1128/jvi.59.2.377-383.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pathak V. K., Temin H. M. 5-Azacytidine and RNA secondary structure increase the retrovirus mutation rate. J Virol. 1992 May;66(5):3093–3100. doi: 10.1128/jvi.66.5.3093-3100.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Pathak V. K., Temin H. M. Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6019–6023. doi: 10.1073/pnas.87.16.6019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Preston B. D., Poiesz B. J., Loeb L. A. Fidelity of HIV-1 reverse transcriptase. Science. 1988 Nov 25;242(4882):1168–1171. doi: 10.1126/science.2460924. [DOI] [PubMed] [Google Scholar]
  25. Ricchetti M., Buc H. E. coli DNA polymerase I as a reverse transcriptase. EMBO J. 1993 Feb;12(2):387–396. doi: 10.1002/j.1460-2075.1993.tb05670.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Roberts J. D., Bebenek K., Kunkel T. A. The accuracy of reverse transcriptase from HIV-1. Science. 1988 Nov 25;242(4882):1171–1173. doi: 10.1126/science.2460925. [DOI] [PubMed] [Google Scholar]
  27. Ronen A., Rahat A. Mutagen specificity and position effects on mutation in T4rII nonsense sites. Mutat Res. 1976 Jan;34(1):21–34. doi: 10.1016/0027-5107(76)90258-x. [DOI] [PubMed] [Google Scholar]
  28. Schubert M., Harmison G. G., Meier E. Primary structure of the vesicular stomatitis virus polymerase (L) gene: evidence for a high frequency of mutations. J Virol. 1984 Aug;51(2):505–514. doi: 10.1128/jvi.51.2.505-514.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schwartz D. E., Tizard R., Gilbert W. Nucleotide sequence of Rous sarcoma virus. Cell. 1983 Mar;32(3):853–869. doi: 10.1016/0092-8674(83)90071-5. [DOI] [PubMed] [Google Scholar]
  30. Sedivy J. M., Capone J. P., RajBhandary U. L., Sharp P. A. An inducible mammalian amber suppressor: propagation of a poliovirus mutant. Cell. 1987 Jul 31;50(3):379–389. doi: 10.1016/0092-8674(87)90492-2. [DOI] [PubMed] [Google Scholar]
  31. Shinnick T. M., Lerner R. A., Sutcliffe J. G. Nucleotide sequence of Moloney murine leukaemia virus. Nature. 1981 Oct 15;293(5833):543–548. doi: 10.1038/293543a0. [DOI] [PubMed] [Google Scholar]
  32. Steinhauer D. A., de la Torre J. C., Holland J. J. High nucleotide substitution error frequencies in clonal pools of vesicular stomatitis virus. J Virol. 1989 May;63(5):2063–2071. doi: 10.1128/jvi.63.5.2063-2071.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Varela-Echavarría A., Garvey N., Preston B. D., Dougherty J. P. Comparison of Moloney murine leukemia virus mutation rate with the fidelity of its reverse transcriptase in vitro. J Biol Chem. 1992 Dec 5;267(34):24681–24688. [PubMed] [Google Scholar]
  34. Ward C. D., Flanegan J. B. Determination of the poliovirus RNA polymerase error frequency at eight sites in the viral genome. J Virol. 1992 Jun;66(6):3784–3793. doi: 10.1128/jvi.66.6.3784-3793.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. de la Torre J. C., Giachetti C., Semler B. L., Holland J. J. High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2531–2535. doi: 10.1073/pnas.89.7.2531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. de la Torre J. C., Wimmer E., Holland J. J. Very high frequency of reversion to guanidine resistance in clonal pools of guanidine-dependent type 1 poliovirus. J Virol. 1990 Feb;64(2):664–671. doi: 10.1128/jvi.64.2.664-671.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]

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