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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
. 1992 Jul 1;89(13):6015–6019. doi: 10.1073/pnas.89.13.6015

Rapid fitness losses in mammalian RNA virus clones due to Muller's ratchet.

E Duarte 1, D Clarke 1, A Moya 1, E Domingo 1, J Holland 1
PMCID: PMC402129  PMID: 1321432

Abstract

Muller's ratchet is an important concept in population genetics. It predicts that when mutation rates are high and a significant proportion of mutations are deleterious, a kind of irreversible ratchet mechanism will gradually decrease the mean fitness of small populations of asexual organisms. In contrast, sexual recombination may stop or reverse this mutational ratchet by recombinational repair of genetic damage. Experimental support for Muller's ratchet has previously been obtained in protozoa and in a tripartite RNA bacteriophage. We now show clear evidence that Muller's ratchet can operate on a nonsegmented nonrecombining pathogenic RNA virus of animals and humans. We did genetic bottleneck passages (plaque-to-plaque transfers) of vesicular somatitis virus (VSV) and then quantitated relative fitness of the bottleneck clones by allowing direct replication competition in mixed infections in cell culture. We document variable fitness drops (some severe) following only 20 plaque-to-plaque transfers of VSV. In some clones no fitness changes (or only insignificant changes) were observed. Surprisingly, the most regular and severe fitness losses occurred during virus passages on a new host cell type. These results again demonstrate the extreme genetic and biological variability of RNA virus populations. Muller's ratchet could have significant implications for variability of disease severity during virus outbreaks, since genetic bottlenecks must often occur during respiratory droplet transmissions and during spread of low-yield RNA viruses from one body site to another (as with human immunodeficiency virus). Likewise, the lower-probability generation of increased-fitness clones during repeated genetic bottleneck transfers of RNA viruses in nature might also affect disease pathogenesis in infected individuals and in host populations. Whenever genetic bottlenecks of RNA viruses occur, enhanced biological differences among viral subpopulations may result.

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Selected References

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

  1. Artenstein M. S., Miller W. S. Air sampling for respiratory disease agents in army recruits. Bacteriol Rev. 1966 Sep;30(3):571–572. doi: 10.1128/br.30.3.571-572.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Coffin J. M. Genetic variation in AIDS viruses. Cell. 1986 Jul 4;46(1):1–4. doi: 10.1016/0092-8674(86)90851-2. [DOI] [PubMed] [Google Scholar]
  4. Felsenstein J. The evolutionary advantage of recombination. Genetics. 1974 Oct;78(2):737–756. doi: 10.1093/genetics/78.2.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gerone P. J., Couch R. B., Keefer G. V., Douglas R. G., Derrenbacher E. B., Knight V. Assessment of experimental and natural viral aerosols. Bacteriol Rev. 1966 Sep;30(3):576–588. doi: 10.1128/br.30.3.576-588.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Green J. B., Smith J. C. Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate. Nature. 1990 Sep 27;347(6291):391–394. doi: 10.1038/347391a0. [DOI] [PubMed] [Google Scholar]
  7. HOLLAND J. J., CORDS C. E. MATURATION OF POLIOVIRUS RNA WITH CAPSID PROTEIN CODED BY HETEROLOGOUS ENTEROVIRUSES. Proc Natl Acad Sci U S A. 1964 Jun;51:1082–1085. doi: 10.1073/pnas.51.6.1082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Holland J. J., de la Torre J. C., Clarke D. K., Duarte E. Quantitation of relative fitness and great adaptability of clonal populations of RNA viruses. J Virol. 1991 Jun;65(6):2960–2967. doi: 10.1128/jvi.65.6.2960-2967.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Lefrancios L., Lyles D. S. The interactionof antiody with the major surface glycoprotein of vesicular stomatitis virus. I. Analysis of neutralizing epitopes with monoclonal antibodies. Virology. 1982 Aug;121(1):157–167. [PubMed] [Google Scholar]
  11. Lefrancois L., Lyles D. S. The interaction of antibody with the major surface glycoprotein of vesicular stomatitis virus. II. Monoclonal antibodies of nonneutralizing and cross-reactive epitopes of Indiana and New Jersey serotypes. Virology. 1982 Aug;121(1):168–174. doi: 10.1016/0042-6822(82)90126-x. [DOI] [PubMed] [Google Scholar]
  12. Martínez M. A., Carrillo C., González-Candelas F., Moya A., Domingo E., Sobrino F. Fitness alteration of foot-and-mouth disease virus mutants: measurement of adaptability of viral quasispecies. J Virol. 1991 Jul;65(7):3954–3957. doi: 10.1128/jvi.65.7.3954-3957.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nee S. Deleterious mutation and genetic recombination. Nature. 1988 Jan 28;331(6154):308–308. doi: 10.1038/331308a0. [DOI] [PubMed] [Google Scholar]
  14. Smith D. B., Inglis S. C. The mutation rate and variability of eukaryotic viruses: an analytical review. J Gen Virol. 1987 Nov;68(Pt 11):2729–2740. doi: 10.1099/0022-1317-68-11-2729. [DOI] [PubMed] [Google Scholar]
  15. Strauss J. H., Strauss E. G. Evolution of RNA viruses. Annu Rev Microbiol. 1988;42:657–683. doi: 10.1146/annurev.mi.42.100188.003301. [DOI] [PubMed] [Google Scholar]
  16. Temin H. M. Is HIV unique or merely different? J Acquir Immune Defic Syndr. 1989;2(1):1–9. [PubMed] [Google Scholar]
  17. Valcárcel J., Ortín J. Phenotypic hiding: the carryover of mutations in RNA viruses as shown by detection of mar mutants in influenza virus. J Virol. 1989 Sep;63(9):4107–4109. doi: 10.1128/jvi.63.9.4107-4109.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Vandepol S. B., Lefrancois L., Holland J. J. Sequences of the major antibody binding epitopes of the Indiana serotype of vesicular stomatitis virus. Virology. 1986 Jan 30;148(2):312–325. doi: 10.1016/0042-6822(86)90328-4. [DOI] [PubMed] [Google Scholar]

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