This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Simmonds, P.
Right arrow Articles by Smith, D. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Simmonds, P.
Right arrow Articles by Smith, D. B.

 Previous Article  |  Next Article 

Journal of Virology, July 1999, p. 5787-5794, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Structural Constraints on RNA Virus Evolution

P. Simmonds* and D. B. Smith

Department of Medical Microbiology, University of Edinburgh, Edinburgh EH8 9AG, United Kingdom

Received 8 February 1999/Accepted 8 April 1999

The recently discovered hepatitis G virus (HGV) or GB virus C (GBV-C) is widely distributed in human populations, and homologues such as HGV/GBV-CCPZ and GBV-A are found in a variety of different primate species. Both epidemiological and phylogenetic analyses support the hypothesis that GB viruses coevolved with their primate hosts, although their degree of sequence similarity appears incompatible with the high rate of sequence change of HGV/GBV-C over short observation periods. Comparison of complete coding sequences (8,500 bases) of different genotypes of HGV/GBV-C showed an excess of invariant synonymous sites (at 23% of all codons) compared with the frequency expected by chance (10%). To investigate the hypothesis that RNA secondary-structure formation through internal base pairing limited sequence variability at these sites, an algorithm was developed to detect covariant sites among HGV/GBV-C sequences of different genotypes. At least 35 covariant sites that were spatially associated with potential stem-loop structures were detected, whose positions correlated with positions in the genome that showed reductions in synonymous variability. Although the functional roles of the predicted secondary structures remain unclear, the restriction of sequence change imposed by secondary-structure formation provides a mechanism for differences in net rate of accumulation of nucleotide substitutions at different sites. However, the resulting disparity between short- and long-term rates of sequence change of HGV/GBV-C violates the assumptions of the "molecular clock." This places a major restriction on the use of nucleotide or amino acid sequence comparisons to calculate times of divergence of other viruses evolving under the same structural constraints as GB viruses.

* Corresponding author. Mailing address: Department of Medical Microbiology, University of Edinburgh, Teviot Place, Edinburgh EH8 9AH, United Kingdom. Phone: 44 131 650 3138. Fax: 44 131 650 6531. E-mail: Peter.Simmonds{at}ed.ac.uk.

Journal of Virology, July 1999, p. 5787-5794, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Williams, C. H., Panayiotou, M., Girling, G. D., Peard, C. I., Oikarinen, S., Hyoty, H., Stanway, G. (2009). Evolution and conservation in human parechovirus genomes. J. Gen. Virol. 90: 1702-1712 [Abstract] [Full Text]  
  • Leitch, E. C. M., Bendig, J., Cabrerizo, M., Cardosa, J., Hyypia, T., Ivanova, O. E., Kelly, A., Kroes, A. C. M., Lukashev, A., MacAdam, A., McMinn, P., Roivainen, M., Trallero, G., Evans, D. J., Simmonds, P. (2009). Transmission Networks and Population Turnover of Echovirus 30. J. Virol. 83: 2109-2118 [Abstract] [Full Text]  
  • Benschop, K., Thomas, X., Serpenti, C., Molenkamp, R., Wolthers, K. (2008). High Prevalence of Human Parechovirus (HPeV) Genotypes in the Amsterdam Region and Identification of Specific HPeV Variants by Direct Genotyping of Stool Samples. J. Clin. Microbiol. 46: 3965-3970 [Abstract] [Full Text]  
  • Wang, Q., Barr, I., Guo, F., Lee, C. (2008). Evidence of a novel RNA secondary structurein the coding region of HIV-1 pol gene. RNA 14: 2478-2488 [Abstract] [Full Text]  
  • Davis, M., Sagan, S. M., Pezacki, J. P., Evans, D. J., Simmonds, P. (2008). Bioinformatic and Physical Characterizations of Genome-Scale Ordered RNA Structure in Mammalian RNA Viruses. J. Virol. 82: 11824-11836 [Abstract] [Full Text]  
  • Hellen, C. U. T., de Breyne, S. (2007). A Distinct Group of Hepacivirus/Pestivirus-Like Internal Ribosomal Entry Sites in Members of Diverse Picornavirus Genera: Evidence for Modular Exchange of Functional Noncoding RNA Elements by Recombination. J. Virol. 81: 5850-5863 [Abstract] [Full Text]  
  • Shapiro, B., Rambaut, A., Pybus, O. G., Holmes, E. C. (2006). A Phylogenetic Method for Detecting Positive Epistasis in Gene Sequences and Its Application to RNA Virus Evolution. Mol Biol Evol 23: 1724-1730 [Abstract] [Full Text]  
  • Simmonds, P., Welch, J. (2006). Frequency and Dynamics of Recombination within Different Species of Human Enteroviruses. J. Virol. 80: 483-493 [Abstract] [Full Text]  
  • Hughes, G. J., Orciari, L. A., Rupprecht, C. E. (2005). Evolutionary timescale of rabies virus adaptation to North American bats inferred from the substitution rate of the nucleoprotein gene. J. Gen. Virol. 86: 1467-1474 [Abstract] [Full Text]  
  • Sall, A. A., Starkman, S., Reynes, J. M., Lay, S., Nhim, T., Hunt, M., Marx, N., Simmonds, P. (2005). Frequent infection of Hylobates pileatus (pileated gibbon) with species-associated variants of hepatitis B virus in Cambodia. J. Gen. Virol. 86: 333-337 [Abstract] [Full Text]  
  • Simmonds, P. (2004). Genetic diversity and evolution of hepatitis C virus - 15 years on. J. Gen. Virol. 85: 3173-3188 [Abstract] [Full Text]  
  • Tuplin, A., Evans, D. J., Simmonds, P. (2004). Detailed mapping of RNA secondary structures in core and NS5B-encoding region sequences of hepatitis C virus by RNase cleavage and novel bioinformatic prediction methods. J. Gen. Virol. 85: 3037-3047 [Abstract] [Full Text]  
  • SIMMONDS, P., TUPLIN, A., EVANS, D. J. (2004). Detection of genome-scale ordered RNA structure (GORS) in genomes of positive-stranded RNA viruses: Implications for virus evolution and host persistence. RNA 10: 1337-1351 [Abstract] [Full Text]  
  • Moury, B. (2004). Differential Selection of Genes of Cucumber Mosaic Virus Subgroups. Mol Biol Evol 21: 1602-1611 [Abstract] [Full Text]  
  • Sanjuan, R., Moya, A., Elena, S. F. (2004). The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus. Proc. Natl. Acad. Sci. USA 101: 8396-8401 [Abstract] [Full Text]  
  • Zlateva, K. T., Lemey, P., Vandamme, A.-M., Van Ranst, M. (2004). Molecular Evolution and Circulation Patterns of Human Respiratory Syncytial Virus Subgroup A: Positively Selected Sites in the Attachment G Glycoprotein. J. Virol. 78: 4675-4683 [Abstract] [Full Text]  
  • Thurner, C., Witwer, C., Hofacker, I. L., Stadler, P. F. (2004). Conserved RNA secondary structures in Flaviviridae genomes. J. Gen. Virol. 85: 1113-1124 [Abstract] [Full Text]  
  • Holmes, E. C. (2003). Patterns of Intra- and Interhost Nonsynonymous Variation Reveal Strong Purifying Selection in Dengue Virus. J. Virol. 77: 11296-11298 [Abstract] [Full Text]  
  • Peleg, O., Trifonov, E. N., Bolshoy, A. (2003). Hidden messages in the nef gene of human immunodeficiency virus type 1 suggest a novel RNA secondary structure. Nucleic Acids Res 31: 4192-4200 [Abstract] [Full Text]  
  • Holmes, E. C. (2003). Molecular Clocks and the Puzzle of RNA Virus Origins. J. Virol. 77: 3893-3897 [Full Text]  
  • Woelk, C. H., Holmes, E. C. (2002). Reduced Positive Selection in Vector-Borne RNA Viruses. Mol Biol Evol 19: 2333-2336 [Full Text]  
  • Lazaro, E., Escarmis, C., Domingo, E., Manrubia, S. C. (2002). Modeling Viral Genome Fitness Evolution Associated with Serial Bottleneck Events: Evidence of Stationary States of Fitness. J. Virol. 76: 8675-8681 [Abstract] [Full Text]  
  • Simmonds, P. (2001). 2000 Fleming Lecture. The origin and evolution of hepatitis viruses in humans. J. Gen. Virol. 82: 693-712 [Abstract] [Full Text]  
  • Cuceanu, N. M., Tuplin, A., Simmonds, P. (2001). Evolutionarily conserved RNA secondary structures in coding and non-coding sequences at the 3' end of the hepatitis G virus/GB-virus C genome. J. Gen. Virol. 82: 713-722 [Abstract] [Full Text]  
  • Worobey, M., Holmes, E. C. (2001). Homologous Recombination in GB Virus C/Hepatitis G Virus. Mol Biol Evol 18: 254-261 [Abstract] [Full Text]  
  • Yuste, E., López-Galíndez, C., Domingo, E. (2000). Unusual Distribution of Mutations Associated with Serial Bottleneck Passages of Human Immunodeficiency Virus Type 1. J. Virol. 74: 9546-9552 [Abstract] [Full Text]  
  • Gavrilin, G. V., Cherkasova, E. A., Lipskaya, G. Y., Kew, O. M., Agol, V. I. (2000). Evolution of Circulating Wild Poliovirus and of Vaccine-Derived Poliovirus in an Immunodeficient Patient: a Unifying Model. J. Virol. 74: 7381-7390 [Abstract] [Full Text]  
  • Korber, B., Muldoon, M., Theiler, J., Gao, F., Gupta, R., Lapedes, A., Hahn, B. H., Wolinsky, S., Bhattacharya, T. (2000). Timing the Ancestor of the HIV-1 Pandemic Strains. Science 288: 1789-1796 [Abstract] [Full Text]  
  • Smith, D. B., Basaras, M., Frost, S., Haydon, D., Cuceanu, N., Prescott, L., Kamenka, C., Millband, D., Sathar, M. A., Simmonds, P. (2000). Phylogenetic analysis of GBV-C/hepatitis G virus. J. Gen. Virol. 81: 769-780 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»