Recombination in hepatitis C virus genotype 1 evaluated by phylogenetic and population-genetic methods.
Although hepatitis C virus (HCV) is a major cause of viral hepatitis and hepatocellular carcinoma, many aspects of its evolution remain poorly understood. Relevant to its evolution and the development of antiviral drug resistance is the role of recombination in HCV, which has not been resolved using phylogenetic tests. In line with previous studies, we found no strong support for a role of recombination in the dominant subtypes 1A and 1B using phylogenetic approaches. In contrast, signatures of gene conversion were abundant if a population recombination model, which takes into account diversity within and between groups, was used (9676 gene conversion signatures between the genomes of subtypes 1A and 1B and 170 between the NS5A regions of subtypes 1A and 1B and the minor subtypes 1c-1g). The gene conversion signatures coincided with a striking lack of diagnostically informative sites between subtypes and a large number of shared mutations between complete subtype 1A and 1B genomes (0.76 and 62.2 % of nucleotide sites, respectively). Maximum-likelihood trees revealed significant topological incongruence among conserved PFAM domains and genome regions targeted by diagnostic assays, which underpins a major role for recombination. The same results were obtained with smaller numbers of genomes and with only synonymous sites. Topological concordance increased only marginally if larger genome regions were compared. The level of recombination in HCV subtype 1, which is probably significantly higher than can currently be measured, also illustrates the complexity of designing diagnostic assays based on the unusual patterns of genomic diversity of HCV.
Department of Pathology, University Medical Centre Groningen, Hanzeplein 1, EA10, PO Box 30.001, 9700 RB Groningen, The Netherlands. t.mes@path.umcg.nl
Ted H M
TH
Mes
Gerard J J
GJ
van Doornum
D015967:Gene Expression Regulation, Viral / Q000502:physiology; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D016865:Reassortant Viruses / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase