Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human

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• dc.contributor.author McCartney, Ann M.
• dc.contributor.author Hyland, Edel M.
• dc.contributor.author Cormican, Paul
• dc.contributor.author Moran, Raymond J.
• dc.contributor.author Webb, Andrew E.
• dc.contributor.author Lee, Kate D.
• dc.contributor.author Hernández Rodríguez, Jéssica, 1983-
• dc.contributor.author Prado Martínez, Javier, 1987-
• dc.contributor.author Creevey, Christopher J.
• dc.contributor.author Aspden, Julie L.
• dc.contributor.author McInerney, James O.
• dc.contributor.author Marquès i Bonet, Tomàs, 1975-
• dc.contributor.author O'Connell, Mary J.
• dc.date.accessioned 2020-03-26T13:57:47Z
• dc.date.available 2020-03-26T13:57:47Z
• dc.date.issued 2019
• dc.description.abstract Gene fusion occurs when two or more individual genes with independent open reading frames becoming juxtaposed under the same open reading frame creating a new fused gene. A small number of gene fusions described in detail have been associated with novel functions, for example, the hominid-specific PIPSL gene, TNFSF12, and the TWE-PRIL gene family. We use Sequence Similarity Networks and species level comparisons of great ape genomes to identify 45 new genes that have emerged by transcriptional readthrough, that is, transcription-derived gene fusion. For 35 of these putative gene fusions, we have been able to assess available RNAseq data to determine whether there are reads that map to each breakpoint. A total of 29 of the putative gene fusions had annotated transcripts (9/29 of which are human-specific). We carried out RT-qPCR in a range of human tissues (placenta, lung, liver, brain, and testes) and found that 23 of the putative gene fusion events were expressed in at least one tissue. Examining the available ribosome foot-printing data, we find evidence for translation of three of the fused genes in human. Finally, we find enrichment for transcription-derived gene fusions in regions of known segmental duplication in human. Together, our results implicate chromosomal structural variation brought about by segmental duplication with the emergence of novel transcripts and translated protein products.
• dc.description.sponsorship The authors would like to thank the following funding agencies: Irish Research Council (IRC) to AMMC (RS/2012/466), Pierse Trust fund, and Orla Benson scholarships to A.M.M.C. 250 Great Minds University of Leeds Fellowship to M.J.O'.C.,IRC to R.J.M. (GOIPG/2014/306), and the Irish Centre for High End Computing (ICHEC) for computational resources. TMB is supported by BFU2017-86471-P (MINECO/FEDER, UE), U01 MH106874 grant, Howard Hughes International Early Career, Obra Social “La Caixa” and Secretaria d'Universitats i Recerca and CERCA Programme del Departament d'Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880).
• dc.format.mimetype application/pdf
• dc.identifier.citation McCartney AM, Hyland EM, Cormican P, Moran RJ, Webb AE, Lee KD, Hernandez-Rodriguez J, Prado-Martinez J, Creevey CJ, Aspden JL, McInerney JO, Marques-Bonet T, O'Connell MJ. Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human. Genome Biol Evol. 2019; 11(9):2678-90. DOI: 10.1093/gbe/evz163
• dc.identifier.doi http://dx.doi.org/10.1093/gbe/evz163
• dc.identifier.issn 1759-6653
• dc.identifier.uri http://hdl.handle.net/10230/44054
• dc.language.iso eng
• dc.publisher Oxford University Press
• dc.relation.ispartof Genome Biol Evol. 2019; 11(9):2678-90
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86471-P
• dc.rights © The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Great Ape Comparative genomics
• dc.subject.keyword Mechanisms of protein-coding evolution
• dc.subject.keyword Novel genes
• dc.subject.keyword Segmental duplication
• dc.subject.keyword Sequence similarity networks
• dc.subject.keyword Transcriptional readthrough
• dc.title Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion