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dc.contributor.authorFirth, Andrewen
dc.date.accessioned2014-10-06T13:36:50Z
dc.date.available2014-10-06T13:36:50Z
dc.date.issued2014-10-17en
dc.identifier.citationNucleic Acids Research 2014, 42 (20): 12425-12439. doi: 10.1093/nar/gku981en
dc.identifier.issn0305-1048
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/246124
dc.description.abstractIdentification of the full complement of genes and other functional elements in any virus is crucial to fully understand its molecular biology and guide the development of effective control strategies. RNA viruses have compact multifunctional genomes that frequently contain overlapping genes and non-coding functional elements embedded within protein-coding sequences. Overlapping features often escape detection because it can be difficult to disentangle the multiple roles of the constituent nucleotides via mutational analyses, while high-throughput experimental techniques are often unable to distinguish functional elements from incidental features. However, RNA viruses evolve very rapidly so that, even within a single species, substitutions rapidly accumulate at neutral or near-neutral sites providing great potential for comparative genomics to distinguish the signature of purifying selection. Computationally identified features can then be efficiently targeted for experimental analysis. Here we analyze alignments of protein-coding virus sequences to identify regions where there is a statistically significant reduction in the degree of variability at synonymous sites, a characteristic signature of overlapping functional elements. Having previously tested this technique by experimental verification of discoveries in selected viruses, we now analyze sequence alignments for ~700 RNA virus species to identify hundreds of such regions, many of which have not been previously described.
dc.description.sponsorshipThis work was supported by the Wellcome Trust [grant number 088789] and the U.K. Biotechnology and Biological Sciences Research Council [grant numbers BB/J007072/1 and BB/J015652/1].
dc.languageEnglishen
dc.language.isoenen
dc.publisherOxford Journals
dc.rightsAttribution 2.0 UK: England & Wales
dc.rightsCreative Commons Attribution License 2.0 UK
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/
dc.titleMapping overlapping functional elements embedded within the protein-coding regions of RNA virusesen
dc.typeArticle
dc.description.versionThis is the final published version. It first appeared at http://nar.oxfordjournals.org/content/42/20/12425.long.en
prism.endingPage12439
prism.publicationDate2014en
prism.publicationNameNucleic Acids Researchen
prism.startingPage12425
prism.volume42en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderBBSRC
dc.rioxxterms.projectid088789
dc.rioxxterms.projectidBB/J007072/1
dc.rioxxterms.projectidBB/J015652/1
rioxxterms.versionofrecord10.1093/nar/gku981en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2014-10-17en
dc.contributor.orcidFirth, Andrew [0000-0002-7986-9520]
dc.identifier.eissn1362-4962
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/J007072/1)
pubs.funder-project-idBBSRC (BB/J015652/1)
pubs.funder-project-idWellcome Trust (088789/Z/09/Z)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales