Viral Evolution and Recombination - Göteborgs...

Viral Evolution and Recombination

Peter [email protected]

Phylogenetic analysis

• Reconstruction of

evolutionary history

• Relationship

• Distance

• Common ancestors

Different representations

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ABCD

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ABCD

Bootstrap

-Construct several new sequence sets (1000 st.)

-A new sequence set is generated by randomly picking of columns from the original set

-Apply the phylogenetic algorithm on all sets.

-Make one consensus tree from all trees

BootstrappingA: AACTTAACCACGCTATCGATGCAATTATATAB: AATTTGACTGCGGTACCGATCCAATTATATAC: AATTTGACTGGGCTACCGATCCAATTATATAD: AACTTAACCGCGCTACTGATCGAATTATATA

A: CACCB: TGCTC: TGCTD: CAGC

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D

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96

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Recombination

Recombination

• Speeds up evolution (up to 10,000 times)

• Accumulate beneficial mutations

• Expel deleterious mutations

Recombination and phylogeny

X

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B

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FG

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I

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Recombination and phylogeny

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Phylogenetic networks

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Methods for detection of recombinants

-Detecting conflicting phylogenetic signals

•Phylogenetic networks (SplitsTree)

•Can be due to recombination or homoplasy

Methods for detection of recombinants

-Analyze conflicting phylogenetic signals, recombination vs homoplasy, and define breakpoints

•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 specific symptoms?)

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

Photo by Linda M. Stannard, University of Cape Town.

• ~100 nm in diameter

• capsid Surrounded by a lipid envelope

• several glycoproteins on the surface

HSV-1 evolution

• sub-genomic phylogeny

• three distinct clades

• recent recombination events

Norberg et al J Virol 2004

US7 US8

HSV-1 recombination analysis



• affecting whole clade

•“ancient” recombination


• Frequency of recombinants?

• Screening based on one or few

loci possible?

• genetic linkage

•=> Complete genome anlaysis!

Norberg Infect Genet Evol 2010

Complete Genome HSV-1 Analysis

• “Star phylogeny”

• Frequent recombination events

• Weak genetic linkage

• Diversity 0.4-1.7%

• 12 complete genomes

• Phylogenetic network

• Clades still present?

Norberg, et al PLoS ONE 2011

HSV-2 evolution

• sub-genomic phylogeny

• strains from Sweden, Norway and

Tanzania

• two “straggling” clades

• frequent recombination events

• => complete genome analysis?




Varicella-Zoster virus (VZV)• chicken pox (varicella), shingles (herpes zoster)

• neurological manifestations, pneumonia, keratitis, …

• spread by aerosol

• > 95%

VZV evolution

• Complete genome analysis

• At least five distinct clades

• Consensus nomenclature

• Diversity 0.1-0.5%

• “Ancient” recombination events

• Few recombinants

• Simple screening

5

1

4

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Norberg 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 years

Recombination

• 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

• Vaccine

The 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 genomes may 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 evolutionary characteristics of VZV

Viral Evolution and Recombination - Göteborgs...

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