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dc.contributor.authorOjosnegros Martos, Samuel-
dc.contributor.authorAgudo, Rubén-
dc.contributor.authorSierra García, Macarena-
dc.contributor.authorBriones, Carlos-
dc.contributor.authorSierra, Saleta-
dc.contributor.authorGonzález-López, Claudia-
dc.contributor.authorDomingo, Esteban-
dc.contributor.authorCristina, Juan-
dc.identifier.citationBMC Evolutionary Biology 2008, 8:207en_US
dc.descriptionAdditional files: Additional file 1: Neighbour-joining, maximum likelihood and maximum parsimony analysis of populations RAp35 and RA0p35. Additional file 2: Maximum likelihood phylogenetic analysis of mutagenized populations of FMDV. Additional file 3: Standard errors.en_US
dc.description.abstractBackground The molecular events and evolutionary forces underlying lethal mutagenesis of virus (or virus extinction through an excess of mutations) are not well understood. Here we apply for the first time phylogenetic methods and Partition Analysis of Quasispecies (PAQ) to monitor genetic distances and intra-population structures of mutant spectra of foot-and-mouth disease virus (FMDV) quasispecies subjected to mutagenesis by base and nucleoside analogues. Results Phylogenetic and PAQ analyses have revealed a highly dynamic variation of intrapopulation diversity of FMDV quasispecies. The population diversity first suffers striking expansions in the presence of mutagens and then compressions either when the presence of the mutagenic analogue was discontinued or when a mutation that decreased sensitivity to a mutagen was selected. The pattern of mutations found in the populations was in agreement with the behavior of the corresponding nucleotide analogues with FMDV in vitro. Mutations accumulated at preferred genomic sites, and dn/ds ratios indicate the operation of negative (or purifying) selection in populations subjected to mutagenesis. No evidence of unusually elevated genetic distances has been obtained for FMDV populations approaching extinction. Conclusion Phylogenetic and PAQ analysis provide adequate procedures to describe the evolution of viral sequences subjected to lethal mutagenesis. These methods define the changes of intra-population structure more precisely than mutation frequencies and Shannon entropies. PAQ is very sensitive to variations of intrapopulation genetic distances. Strong negative (or purifying) selection operates in FMDV populations subjected to enhanced mutagenesis. The quantifications provide evidence that extinction does not imply unusual increases of intrapopulation complexity, in support of the lethal defection model of virus extinction.en_US
dc.description.sponsorshipWork at Centro de Biología Molecular "Severo Ochoa" was supported by grants BFU2006-00863 from MEC, 36558/06 from FIPSE, and Fundación R.Areces. Work at Centro de Astrobiología was supported by INTA, MEC, CAM and UE. CIBERehd is funded by Instituto de Salud Carlos III. S.O. was supported by a predoctoral fellowship from the Ministerio de Educacion y Ciencia.en_US
dc.format.extent1725473 bytes-
dc.publisherBioMed Centralen_US
dc.relation.isversionofPublisher’s version-
dc.subjectPartition Analysis of Quasispeciesen_US
dc.titleTopology of evolving, mutagenized viral populations: quasispecies expansion, compression, and operation of negative selectionen_US
dc.description.peerreviewedPeer revieweden_US
dc.contributor.funderMinisterio de Educación y Ciencia (España)-
dc.contributor.funderFundación para la Investigación y la Prevención del Sida en España-
dc.contributor.funderFundación Ramón Areces-
dc.contributor.funderInstituto Nacional de Técnica Aeroespacial (España)-
dc.contributor.funderEuropean Commission-
dc.contributor.funderInstituto de Salud Carlos III-
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