Bayesian Coalescent Analysis Reveals a High Rate of Molecular Evolution in GB Virus C
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GB virus C/hepatitis G (GBV-C) is an RNA virus of the family Flaviviridae. Despite replicating with an RNA-dependent RNA polymerase, some previous estimates of rates of evolutionary change in GBV-C suggest that it fixes mutations at the anomalously low rate of ∼10−7 nucleotide substitution per site, per year. However, these estimates were largely based on the assumption that GBV-C and its close relative GBV-A (New World monkey GB viruses) codiverged with their primate hosts over millions of years. Herein, we estimated the substitution rate of GBV-C using the largest set of dated GBV-C isolates compiled to date and a Bayesian coalescent approach that utilizes the year of sampling and so is independent of the assumption of codivergence. This revealed a rate of evolutionary change approximately four orders of magnitude higher than that estimated previously, in the range of 10−2 to 10−3 sub/site/year, and hence in line with those previously determined for RNA viruses in general and the Flaviviridae in particular. In addition, we tested the assumption of host-virus codivergence in GBV-A by performing a reconciliation analysis of host and virus phylogenies. Strikingly, we found no statistical evidence for host-virus codivergence in GBV-A, indicating that substitution rates in the GB viruses should not be estimated from host divergence times.
KeywordsGB virus C Molecular clock Substitution rate Codivergence Phylogeny Coalescent theory
We thank Dr. H. Hotta, Dr. A. Sathar, Dr. S. Muerhoff, Dr. J. Stapleton, Dr. S. Ross, Dr. K. Abe, Dr. P. Gobau, Dr. A. M. Bisceglie, and Dr. M. Tacácks for kindly providing additional information concerning the sequences used in this study. The research undertaken in this study was funded in part by NIH Grant GM080533-01.
- Abe K (2001) GB virus-C/hepatiitis G virus. Japan J Infect Dis 54:55–63Google Scholar
- Charleston MA, Page RDM (2002) Treemap, version 20 Available at: http://www.taxonomy.zoology.gla.ac.uk/mac/treemap/index.html
- Hershkovitz P (1977) Living New World monkeys (Platyrrhini). University of Chicago Press, ChicagoGoogle Scholar
- Linnen J, Wages J Jr, Zhang-Keck ZY, Fry KE, Krawczynski KZ, Alter H, Koonin E, Gallagher M, Alter M, Hadziyannis S, Karayiannis P, Fung K, Nakatsuji Y, Shih JW, Young L, Piatak M Jr, Hoover C, Fernandez J, Chen S, Zou JC, Morris T, Hyams KC, Ismay S, Lifson JD, Hess G, Foung SK, Thomas H, Bradley D, Margolis H, Kim JP (1996) Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science 26:505–508CrossRefGoogle Scholar
- Moaven LD, Hyland CA, Young IF, Bowden DS, McCaw R, Mison L, Locarnini SA (1996) Prevalence of hepatitis G virus in Queensland blood donors. Med J Aust 7:369–371Google Scholar
- Swofford DL (2003) PAUP*: Phylogenetic Analysis Using Parsimony (*and other methods) Version 4. Sinauer Associates, Sunderland, MAGoogle Scholar