Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1993 Jan;67(1):222–228. doi: 10.1128/jvi.67.1.222-228.1993

Genetic bottlenecks and population passages cause profound fitness differences in RNA viruses.

D K Clarke 1, E A Duarte 1, A Moya 1, S F Elena 1, E Domingo 1, J Holland 1
PMCID: PMC237355  PMID: 8380072

Abstract

Repeated clone-to-clone (genetic bottleneck) passages of an RNA phage and vesicular stomatitis virus have been shown previously to result in loss of fitness due to Muller's ratchet. We now demonstrate that Muller's ratchet also operates when genetic bottleneck passages are carried out at 37 rather than 32 degrees C. Thus, these fitness losses do not depend on growth of temperature-sensitive (ts) mutants at lowered temperatures. We also demonstrate that during repeated genetic bottleneck passages, accumulation of deleterious mutations does occur in a stepwise (ratchet-like) manner as originally proposed by Muller. One selected clone which had undergone significant loss of fitness after only 20 genetic bottleneck passages was passaged again in clone-to-clone series. Additional large losses of fitness were observed in five of nine independent bottleneck series; the relative fitnesses of the other four series remained close to the starting fitness. In sharp contrast, when the same selected clone was transferred 20 more times as large populations (10(5) to 10(6) PFU transferred at each passage), significant increases in fitness were observed in all eight passage series. Finally, we selected several clones which had undergone extreme losses of fitness during 20 bottleneck passages. When these low-fitness clones were passaged many times as large virus populations, they always regained very high relative fitness. We conclude that transfer of large populations of RNA viruses regularly selects those genomes within the quasispecies population which have the highest relative fitness, whereas bottleneck transfers have a high probability of leading to loss of fitness by random isolation of genomes carrying debilitating mutations. Both phenomena arise from, and underscore, the extreme mutability and variability of RNA viruses.

Full text

PDF
222

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. Benmansour A., Brahimi M., Tuffereau C., Coulon P., Lafay F., Flamand A. Rapid sequence evolution of street rabies glycoprotein is related to the highly heterogeneous nature of the viral population. Virology. 1992 Mar;187(1):33–45. doi: 10.1016/0042-6822(92)90292-w. [DOI] [PubMed] [Google Scholar]
  3. Bilsel P. A., Nichol S. T. Polymerase errors accumulating during natural evolution of the glycoprotein gene of vesicular stomatitis virus Indiana serotype isolates. J Virol. 1990 Oct;64(10):4873–4883. doi: 10.1128/jvi.64.10.4873-4883.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cattaneo R., Billeter M. A. Mutations and A/I hypermutations in measles virus persistent infections. Curr Top Microbiol Immunol. 1992;176:63–74. doi: 10.1007/978-3-642-77011-1_5. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Chao L. Levels of selection, evolution of sex in RNA viruses, and the origin of life. J Theor Biol. 1991 Nov 21;153(2):229–246. doi: 10.1016/s0022-5193(05)80424-2. [DOI] [PubMed] [Google Scholar]
  7. Chattopadhyay S. K., Morse H. C., 3rd, Makino M., Ruscetti S. K., Hartley J. W. Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1989 May;86(10):3862–3866. doi: 10.1073/pnas.86.10.3862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coffin J. M. Genetic diversity and evolution of retroviruses. Curr Top Microbiol Immunol. 1992;176:143–164. doi: 10.1007/978-3-642-77011-1_10. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Couch R. B., Cate T. R., Douglas R. G., Jr, Gerone P. J., Knight V. Effect of route of inoculation on experimental respiratory viral disease in volunteers and evidence for airborne transmission. Bacteriol Rev. 1966 Sep;30(3):517–529. doi: 10.1128/br.30.3.517-529.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DE JONG J. G., WINKLER K. C. SURVIVAL OF MEASLES VIRUS IN AIR. Nature. 1964 Mar 7;201:1054–1055. doi: 10.1038/2011054a0. [DOI] [PubMed] [Google Scholar]
  12. Domingo E., Escarmis C., Martinez M. A., Martinez-Salas E., Mateu M. G. Foot-and-mouth disease virus populations are quasispecies. Curr Top Microbiol Immunol. 1992;176:33–47. doi: 10.1007/978-3-642-77011-1_3. [DOI] [PubMed] [Google Scholar]
  13. Domingo E., Martínez-Salas E., Sobrino F., de la Torre J. C., Portela A., Ortín J., López-Galindez C., Pérez-Breña P., Villanueva N., Nájera R. The quasispecies (extremely heterogeneous) nature of viral RNA genome populations: biological relevance--a review. Gene. 1985;40(1):1–8. doi: 10.1016/0378-1119(85)90017-4. [DOI] [PubMed] [Google Scholar]
  14. Domingo E. RNA virus evolution and the control of viral disease. Prog Drug Res. 1989;33:93–133. doi: 10.1007/978-3-0348-9146-2_5. [DOI] [PubMed] [Google Scholar]
  15. Duarte E., Clarke D., Moya A., Domingo E., Holland J. Rapid fitness losses in mammalian RNA virus clones due to Muller's ratchet. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6015–6019. doi: 10.1073/pnas.89.13.6015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. ENDERS J. F., KATZ S. L., HOLLOWAY A. Development of attenuated measles-virus vaccines. A summary of recentinvestigation. Am J Dis Child. 1962 Mar;103:335–340. doi: 10.1001/archpedi.1962.02080020347030. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Fitch W. M., Leiter J. M., Li X. Q., Palese P. Positive Darwinian evolution in human influenza A viruses. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4270–4274. doi: 10.1073/pnas.88.10.4270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Gorman O. T., Bean W. J., Webster R. G. Evolutionary processes in influenza viruses: divergence, rapid evolution, and stasis. Curr Top Microbiol Immunol. 1992;176:75–97. doi: 10.1007/978-3-642-77011-1_6. [DOI] [PubMed] [Google Scholar]
  21. Holland J. J., De La Torre J. C., Steinhauer D. A. RNA virus populations as quasispecies. Curr Top Microbiol Immunol. 1992;176:1–20. doi: 10.1007/978-3-642-77011-1_1. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Kinnunen L., Pöyry T., Hovi T. Genetic diversity and rapid evolution of poliovirus in human hosts. Curr Top Microbiol Immunol. 1992;176:49–61. doi: 10.1007/978-3-642-77011-1_4. [DOI] [PubMed] [Google Scholar]
  24. Kondrashov A. S. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. doi: 10.1038/336435a0. [DOI] [PubMed] [Google Scholar]
  25. Kurath G., Palukaitis P. Serial passage of infectious transcripts of a cucumber mosaic virus satellite RNA clone results in sequence heterogeneity. Virology. 1990 May;176(1):8–15. doi: 10.1016/0042-6822(90)90224-f. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Lefrancois L., Lyles D. S. Antigenic determinants of vesicular stomatitis virus: analysis with antigenic variants. J Immunol. 1983 Jan;130(1):394–398. [PubMed] [Google Scholar]
  28. 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]
  29. MULLER H. J. THE RELATION OF RECOMBINATION TO MUTATIONAL ADVANCE. Mutat Res. 1964 May;106:2–9. doi: 10.1016/0027-5107(64)90047-8. [DOI] [PubMed] [Google Scholar]
  30. Martínez M. A., Dopazo J., Hernández J., Mateu M. G., Sobrino F., Domingo E., Knowles N. J. Evolution of the capsid protein genes of foot-and-mouth disease virus: antigenic variation without accumulation of amino acid substitutions over six decades. J Virol. 1992 Jun;66(6):3557–3565. doi: 10.1128/jvi.66.6.3557-3565.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Meyerhans A., Cheynier R., Albert J., Seth M., Kwok S., Sninsky J., Morfeldt-Månson L., Asjö B., Wain-Hobson S. Temporal fluctuations in HIV quasispecies in vivo are not reflected by sequential HIV isolations. Cell. 1989 Sep 8;58(5):901–910. doi: 10.1016/0092-8674(89)90942-2. [DOI] [PubMed] [Google Scholar]
  32. Mudd J. A., Summers D. F. Protein synthesis in vesicular stomatitis virus-infected HeLa cells. Virology. 1970 Oct;42(2):328–340. doi: 10.1016/0042-6822(70)90277-1. [DOI] [PubMed] [Google Scholar]
  33. Nee S. Deleterious mutation and genetic recombination. Nature. 1988 Jan 28;331(6154):308–308. doi: 10.1038/331308a0. [DOI] [PubMed] [Google Scholar]
  34. Nee S. On the evolution of sex in RNA viruses. J Theor Biol. 1989 Jun 8;138(3):407–412. doi: 10.1016/s0022-5193(89)80201-2. [DOI] [PubMed] [Google Scholar]
  35. Nowak M. A., Anderson R. M., McLean A. R., Wolfs T. F., Goudsmit J., May R. M. Antigenic diversity thresholds and the development of AIDS. Science. 1991 Nov 15;254(5034):963–969. doi: 10.1126/science.1683006. [DOI] [PubMed] [Google Scholar]
  36. Overbaugh J., Donahue P. R., Quackenbush S. L., Hoover E. A., Mullins J. I. Molecular cloning of a feline leukemia virus that induces fatal immunodeficiency disease in cats. Science. 1988 Feb 19;239(4842):906–910. doi: 10.1126/science.2893454. [DOI] [PubMed] [Google Scholar]
  37. Pang S., Shlesinger Y., Daar E. S., Moudgil T., Ho D. D., Chen I. S. Rapid generation of sequence variation during primary HIV-1 infection. AIDS. 1992 May;6(5):453–460. doi: 10.1097/00002030-199205000-00003. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. Santantonio T., Jung M. C., Miska S., Pastore G., Pape G. R., Will H. Prevalence and type of pre-C HBV mutants in anti-HBe positive carriers with chronic liver disease in a highly endemic area. Virology. 1991 Aug;183(2):840–844. doi: 10.1016/0042-6822(91)91022-9. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. 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]
  43. Vartanian J. P., Meyerhans A., Asjö B., Wain-Hobson S. Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes. J Virol. 1991 Apr;65(4):1779–1788. doi: 10.1128/jvi.65.4.1779-1788.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wain-Hobson S. Human immunodeficiency virus type 1 quasispecies in vivo and ex vivo. Curr Top Microbiol Immunol. 1992;176:181–193. doi: 10.1007/978-3-642-77011-1_12. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Wolinsky S. M., Wike C. M., Korber B. T., Hutto C., Parks W. P., Rosenblum L. L., Kunstman K. J., Furtado M. R., Muñoz J. L. Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science. 1992 Feb 28;255(5048):1134–1137. doi: 10.1126/science.1546316. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES