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dc.contributor.authorFARES, MARIOen
dc.date.accessioned2010-12-07T18:50:27Z
dc.date.available2010-12-07T18:50:27Z
dc.date.issued2010en
dc.date.submitted2010en
dc.identifier.citationCodoner, FM, Alfonso-Loeches, S, Fares, MA, Mutational dynamics of murine angiogenin duplicates, BMC Evolutionary Biology, 10, 1, 2010, 310en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/41243
dc.descriptionPUBLISHEDen
dc.description.abstractBackground: Angiogenin (Ang) is a protein involved in angiogenesis by inducing the formation of blood vessels. The biomedical importance of this protein has come from findings linking mutations in Ang to cancer progression and neurodegenerative diseases. These findings highlight the evolutionary constrain on Ang amino acid sequence. However, previous studies comparing human Angiogenin with homologs from other phylogenetically related organisms have led to the conclusion that Ang presents a striking variability. Whether this variability has an adaptive value per se remains elusive. Understanding why many functional Ang paralogs have been preserved in mouse and rat and identifying functional divergence mutations at these copies may explain the relationship between mutations and function. In spite of the importance of testing this hypothesis from the evolutionarily and biomedical perspectives, this remains yet unaccomplished. Here we test the main mutational dynamics driving the evolution and function of Ang paralogs in mammals. Results: We analysed the phylogenetic asymmetries between the different Ang gene copies in mouse and rat in the context of vertebrate Ang phylogeny. This analysis shows strong evidence in support of accelerated evolution in some Ang murine copies (mAng). This acceleration is not due to non-functionalisation because constraints on amino acid replacements remain strong. We identify many of the amino acid sites involved in signal localization and nucleotide binding by Ang to have evolved under diversifying selection. Compensatory effects of many of the mutations at these paralogs and their key structural location in or nearby important functional regions support a possible functional shift (functional divergence) in many Ang copies. Similarities between 3D-structural models for mAng copies suggest that their divergence is mainly functional. Conclusions: We identify the main evolutionary dynamics shaping the variability of Angiogenin in vertebrates and highlight the plasticity of this protein after gene duplication. Our results suggest functional divergence among mAng paralogs. This puts forward mAng as a good system candidate for testing functional plasticity of such an important protein while stresses caution when using mouse as a model to infer the consequences of mutations in the single Ang copy of humans.en
dc.description.sponsorshipThis work was supported by Science Foundation Ireland to M.A.F (04/YI1/ M518). F.M.C. was supported by Marie Curie European Reintegration Grant FP7 actions (238885). S.A.L. is supported by a FPI PhD grant from the Spanish Ministerio de Ciencia y Tecnologia.en
dc.format.extent310en
dc.language.isoenen
dc.relation.ispartofseriesBMC Evolutionary Biologyen
dc.relation.ispartofseries10en
dc.relation.ispartofseries1en
dc.rightsYen
dc.subjectAMYOTROPHIC-LATERAL-SCLEROSISen
dc.subjectSITE-DIRECTED MUTAGENESISen
dc.subjectDETECT SELECTIVE CONSTRAINTSen
dc.subjectRIBONUCLEASE-A SUPERFAMILYen
dc.subjectFUNCTIONAL DIVERGENCEen
dc.subjectSTRUCTURAL FEATURESen
dc.subjectMONOCLONAL-ANTIBODYen
dc.subjectTUMOR-GROWTHen
dc.subject.meshtest
dc.titleMutational dynamics of murine angiogenin duplicatesen
dc.typeJournal Articleen
dc.contributor.sponsorEuropean Commissionen
dc.contributor.sponsorScience Foundation Ireland (SFI)en
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/faresmen
dc.identifier.rssinternalid69919en
dc.identifier.doihttp://dx.doi.org/10.1186/1471-2148-10-310en
dc.relation.ecprojectidinfo:eu-repo/grantAgreement/EC/FP7/04/YI1/M518
dc.rights.ecaccessrightsOpenAccess
dc.rights.ecaccessrightsinfo:eu-repo/semantics/openAccessen
dc.contributor.sponsorGrantNumber238885en
dc.contributor.sponsorGrantNumber04/YI1/M518en
dc.subject.TCDThemeGenes & Societyen


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