Exon creation and establishment in human genes

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• dc.contributor.author Corvelo, Andréca
• dc.contributor.author Eyras Jiménez, Eduardoca
• dc.date.accessioned 2016-05-02T14:26:34Z
• dc.date.available 2016-05-02T14:26:34Z
• dc.date.issued 2008
• dc.description.abstract BACKGROUND: A large proportion of species-specific exons are alternatively spliced. In primates, Alu elements play a crucial role in the process of exon creation but many new exons have appeared through other mechanisms. Despite many recent studies, it is still unclear which are the splicing regulatory requirements for de novo exonization and how splicing regulation changes throughout an exon's lifespan. RESULTS: Using comparative genomics, we have defined sets of exons with different evolutionary ages. Younger exons have weaker splice-sites and lower absolute values for the relative abundance of putative splicing regulators between exonic and adjacent intronic regions, indicating a less consolidated splicing regulation. This relative abundance is shown to increase with exon age, leading to higher exon inclusion. We show that this local difference in the density of regulators might be of biological significance, as it outperforms other measures in real exon versus pseudo-exon classification. We apply this new measure to the specific case of the exonization of anti-sense Alu elements and show that they are characterized by a general lack of exonic splicing silencers. CONCLUSIONS: Our results suggest that specific sequence environments are required for exonization and that these can change with time. We propose a model of exon creation and establishment in human genes, in which splicing decisions depend on the relative local abundance of regulatory motifs. Using this model, we provide further explanation as to why Alu elements serve as a major substrate for exon creation in primates. Finally, we discuss the benefits of integrating such information in gene prediction.ca
• dc.description.sponsorship The authors would like to thank J Brosius for useful comments on the manuscript, M Plass (funded by the Spanish Health Institute Carlos III) for EST data handling and R Castelo (funded by the Spanish Ministry of Science) for the splice site position weight matrices. AC received support from the Graduate Program in Areas of Basic and Applied Biology (GABBA) and the Portuguese Foundation for Science and Technology. EE is supported by the Catalan Institution of Research and Advanced Studies (ICREA). This work is partly supported by the grant BIO2005-01287 from the Spanish Ministry of Science and by the project EURASNET from the European Commission.
• dc.format.mimetype application/pdfca
• dc.identifier.citation Corvelo A, Eyras E. Exon creation and establishment in human genes. Genome biology. 2008;9(9):R141. DOI: 10.1186/gb-2008-9-9-r141ca
• dc.identifier.doi http://dx.doi.org/10.1186/gb-2008-9-9-r141
• dc.identifier.issn 1474-7596
• dc.identifier.uri http://hdl.handle.net/10230/26232
• dc.language.iso engca
• dc.publisher BioMed Centralca
• dc.relation.ispartof Genome biology. 2008;9(9):R141
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PN/BIO2005-01287
• dc.rights © 2008 Corvelo and Eyras; licensee BioMed Central Ltd. /nThis is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.ca
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.rights.uri http://creativecommons.org/licenses/by/2.0ca
• dc.subject.other Evolució molecularca
• dc.subject.other Exonsca
• dc.title Exon creation and establishment in human genesca
• dc.type info:eu-repo/semantics/articleca
• dc.type.version info:eu-repo/semantics/publishedVersionca