Viral Evolution And Recombination - Göteborgs Universitet

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Viral Evolution andRecombinationPeter Norbergpeter.norberg@gu.sePhylogenetic analysis Reconstruction ofevolutionary history Relationship Distance Common ancestors

Different representationsA B C DABABCDABCDCDABCDBootstrap-Construct several new sequence sets (1000 st.)-A new sequence set is generated by randomlypicking of columns from the original set-Apply the phylogenetic algorithm on all sets.-Make one consensus tree from all trees

BootstrappingA: AACTTAACCACGCTATCGATGCAATTATATAB: AATTTGACTGCGGTACCGATCCAATTATATAC: AATTTGACTGGGCTACCGATCCAATTATATAD: AACTTAACCGCGCTACTGATCGAATTATATAA: CACCB: TGCTC: TGCTD: CAGCAA196CD1CRecombinationBBB96A3C3DD

Recombination Speeds up evolution (up to 10,000 times) Accumulate beneficial mutations Expel deleterious mutationsRecombination and phylogenyXHCACADDEEHBIFGHBIFG

Recombination and phylogenyHXCADEHBIFGPhylogenetic networksHXCADEHBIFG

Methods for detection ofrecombinants-Detecting conflicting phylogenetic signals Phylogenetic networks (SplitsTree) Can be due to recombination or homoplasyMethods for detection ofrecombinants-Analyze conflicting phylogenetic signals,recombination vs homoplasy, and definebreakpoints Bootscan (SimPlot) Similarity plots (SimPlot) Statistical tests (phi-test) RDP, Geneconv, MaxChi, Chimaera, SisScan,3Sec, LARD, Topal, . (RDP)

Viral phylogeny and genetics Genetic diversity Evolutionary history Evolutionary mechanisms Genotype/phenotype association studies(Genetic markers responsible for specificsymptoms?)Herpes simplex virus type 1 and 2 oral (HSV-1) or genital (HSV-2) lesions. encephalitis, meningitis, keratitis, spread via direct contact Establish latency in sensorial ganglia 60-80% asymptomatic infections common 100 nm in diameter capsid Surrounded by a lipidenvelope several glycoproteins on thesurfacePhoto by Linda M. Stannard, University of Cape Town.

HSV-1 evolution sub-genomic phylogeny three distinct cladesUS7US8 recent recombination eventsNorberg et al J Virol 2004HSV-1 recombination analysisNorberg et al J Virol 2004

HSV-1 recombination analysis affecting whole clade “ancient” recombinationNorberg et al J Virol 2004 Frequency of recombinants? Screening based on one or fewloci possible? genetic linkage Complete genome anlaysis!Norberg Infect Genet Evol 2010

Complete Genome HSV-1 Analysis 12 complete genomes Phylogenetic network Clades still present? “Star phylogeny” Frequent recombination events Weak genetic linkage Diversity 0.4-1.7%Norberg, et al PLoS ONE 2011

HSV-2 evolution sub-genomic phylogeny strains from Sweden, Norway andTanzania two “straggling” clades frequent recombination events complete genome analysis?Norberg et al J Virol 2007HSV-2recombinationanalysisNorberg et al J Virol 2007

Varicella-Zoster virus (VZV) chicken pox (varicella), shingles (herpes zoster) neurological manifestations, pneumonia, keratitis, spread by aerosol 95%VZV evolution5 Complete genome analysis At least five distinct clades Consensus nomenclature23 Diversity 0.1-0.5% “Ancient” recombination events Few recombinants Simple screening14Norberg et al J Virol 2006, Peters et al J Virol 2006, Breuer et al J Gen Virol 2010

Time since divergence VZV:60,000 - 100,000 years HSV-1: 400,000 - 700,000 yearsRecombination Why so low frequency of VZV recombinants? Why only ancient and not recent recombinants? Likely to have the same ability to recombine VZV easily recombines in animal models Recent VZV “Intra clade” recombination

Recombination Geographic separation About to fade out Immigration VaccineThe future?

Summary herpesvirus evolution Each virus evolved to different clades Genetic variability:- HSV-1 : 3%- HSV-2 : 0,5%- VZV : 0,2% Recombinants common Recombination is a general mechanism in the evolution of human -herpesviruses– Most common for HSV-2, followed by HSV-1. Least common for VZV In combination with different genotypes, infinite numbers of different mosaic genomesmay arise Genotyping of complete HSV-1 genomes into clades irrelevant! Differences in geographic distribution (HSV-1 more mixed than VZV) May change due to migration and vaccination! The mosaic genetics of HSV-1 can be a plausible indicator on future evolutionarycharacteristics of VZV

Peter Norberg peter.norberg@gu.se Phylogenetic analysis Reconstruction of evolutionary history Relationship Distance . RDP, Geneconv, MaxChi, Chimaera, SisScan, 3Sec, LARD, Topal, . (RDP) Viral phylogeny and genetics Genetic diversity Evolutionary history Evolutionary mechanisms Genotype/phenotype association studies

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