Recombination and Population Mosaic of a Multifunctional Viral Gene, Adeno-Associated Virus cap 英文参考文献.docVIP
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Recombination and Population Mosaic of a Multifunctional Viral Gene, Adeno-Associated Virus cap 英文参考文献
RecombinationandPopulationMosaicofa
MultifunctionalViralGene,Adeno-AssociatedViruscap
YasuhiroTakeuchi1*,RichardMyers1,2,OlivierDanos1,3
1MedicalReserachCouncil(MRC)/UCLCentreforMedicalMolecularVirology,DivisionofInfectionandImmunology,UniversityCollegeLondon,London,UnitedKingdom,
2CentreforInfections,HealthProtectionAgency,London,UnitedKingdom,3InstitutNationaldelaSante′ etdelaRechercheMe′dicale (INSERM),U781,InstitutFe′de′ratif
deRechercheNeckerEnfantsMalades(IFR94),Ho?pitalNeckerEnfantsMalades,Paris,France
Abstract
Homologous recombination is a dominant force in evolution and results in genetic mosaics. To detect evidence of
recombination events and assess the biological significance of genetic mosaics, genome sequences for various viral
populationsofreasonablylargesizearenowavailableintheGenBank.Westudiedamulti-functionalviralgene,theadeno-
associatedvirus(AAV)capgene,whichcodesforthreecapsidproteins,VP1,VP2andVP3.VP1-3shareacommonC-terminal
domain corresponding to VP3, which forms the viral core structure, while the VP1 unique N-terminal part contains an
enzymatic domain with phospholipase A2 activity. Our recombinant detection program (RecI) revealed five novel
recombinationevents,fourofwhichhavetheircross-overpointsintheN-terminal,VP1andVP2uniqueregion.Comparison
of phylogenetic trees for different cap gene regions confirmed discordant phylogenies for the recombinant sequences.
Furthermore, differences in the phylogenetic tree structures for the VP1 unique (VP1u) region and the rest of cap
highlightedthemosaicnatureofcapgeneintheAAVpopulation:twodominantformsofVP1usequenceswereidentified
and these forms are linked to diverse sequences in the rest of cap gene. This observation together with the finding of
frequent recombination in the VP1 and 2 unique regions suggests that this region is a recombination hot spot.
RecombinationeventsinthisregionpreserveproteinblocksofdistinctivefunctionsandcontributetoconvergenceinVP1u
anddivergenceoftherestofcap.Add
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