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Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation
Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, South Parks Road, Oxford OX1 3SY, UK
Fiji School of Medicine, Suva, Fiji
Department of Microbiology and Immunology, Rega Institute, K.U. Leuven 3000, Belgium
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA, UK
The Hepatitis Foundation of New Zealand, Ohope, Whakatane 3121, New Zealand
Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany
School of Medicine and Health Sciences, University of Papua New Guinea, P.O. Box 5623, Boroko, Port Moresby, NCD, Papua New Guinea
Nawerwere Hospital, Kiribati Ministry of Health, Tawara, Kiribati
Allan Wilson Centre for Molecular Ecology and Evolution, Massey University, Palmerston North 4442, New Zealand
Ashworth Laboratories, Institute of Evolutionary Biology, King’s Buildings, Edinburgh, EH8 3JT, UK
Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, USA
Department of Biology, The Pennsylvania State University, University Park, PA 16802, USA
* Authors to whom correspondence should be addressed.
Received: 3 December 2010; in revised form: 6 January 2011 / Accepted: 6 January 2011 / Published: 25 January 2011
Abstract: Hepatitis B virus (HBV) genomes are small, semi-double-stranded DNA circular genomes that contain alternating overlapping reading frames and replicate through an RNA intermediary phase. This complex biology has presented a challenge to estimating an evolutionary rate for HBV, leading to difficulties resolving the evolutionary and epidemiological history of the virus. Here, we re-examine rates of HBV evolution using a novel data set of 112 within-host, transmission history (pedigree) and among-host genomes isolated over 20 years from the indigenous peoples of the South Pacific, combined with 313 previously published HBV genomes. We employ Bayesian phylogenetic approaches to examine several potential causes and consequences of evolutionary rate variation in HBV. Our results reveal rate variation both between genotypes and across the genome, as well as strikingly slower rates when genomes are sampled in the Hepatitis B e antigen positive state, compared to the e antigen negative state. This Hepatitis B e antigen rate variation was found to be largely attributable to changes during the course of infection in the preCore and Core genes and their regulatory elements.
Keywords: hepatitis B virus; molecular clock; Bayesian phylogenetics
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Harrison, A.; Lemey, P.; Hurles, M.; Moyes, C.; Horn, S.; Pryor, J.; Malani, J.; Supuri, M.; Masta, A.; Teriboriki, B.; Toatu, T.; Penny, D.; Rambaut, A.; Shapiro, B. Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation. Viruses 2011, 3, 83-101.
Harrison A, Lemey P, Hurles M, Moyes C, Horn S, Pryor J, Malani J, Supuri M, Masta A, Teriboriki B, Toatu T, Penny D, Rambaut A, Shapiro B. Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation. Viruses. 2011; 3(2):83-101.
Harrison, Abby; Lemey, Philippe; Hurles, Matthew; Moyes, Chris; Horn, Susanne; Pryor, Jan; Malani, Joji; Supuri, Mathias; Masta, Andrew; Teriboriki, Burentau; Toatu, Tebuka; Penny, David; Rambaut, Andrew; Shapiro, Beth. 2011. "Genomic Analysis of Hepatitis B Virus Reveals Antigen State and Genotype as Sources of Evolutionary Rate Variation." Viruses 3, no. 2: 83-101.