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

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 P...

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Autores: McCartney, Ann M., Hyland, Edel M., Cormican, Paul, Moran, Raymond J., Webb, Andrew E., Lee, Kate D., Hernández Rodríguez, Jéssica, 1983-, Prado Martínez, Javier, 1987-, Creevey, Christopher J., Aspden, Julie L., McInerney, James O., Marquès i Bonet, Tomàs, 1975-, O'Connell, Mary J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/44054
Acceso en línea:http://hdl.handle.net/10230/44054
http://dx.doi.org/10.1093/gbe/evz163
Access Level:acceso abierto
Palabra clave:Great Ape Comparative genomics
Mechanisms of protein-coding evolution
Novel genes
Segmental duplication
Sequence similarity networks
Transcriptional readthrough
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spelling Gene fusions derived by transcriptional readthrough are driven by segmental duplication in humanMcCartney, Ann M.Hyland, Edel M.Cormican, PaulMoran, Raymond J.Webb, Andrew E.Lee, Kate D.Hernández Rodríguez, Jéssica, 1983-Prado Martínez, Javier, 1987-Creevey, Christopher J.Aspden, Julie L.McInerney, James O.Marquès i Bonet, Tomàs, 1975-O'Connell, Mary J.Great Ape Comparative genomicsMechanisms of protein-coding evolutionNovel genesSegmental duplicationSequence similarity networksTranscriptional readthroughGene 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.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).Oxford University Press202020202019info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/44054http://dx.doi.org/10.1093/gbe/evz163reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésGenome Biol Evol. 2019; 11(9):2678-90info:eu-repo/grantAgreement/ES/2PE/BFU2017-86471-P© 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.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/440542026-05-29T05:05:01Z
dc.title.none.fl_str_mv Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
title Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
spellingShingle Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
McCartney, Ann M.
Great Ape Comparative genomics
Mechanisms of protein-coding evolution
Novel genes
Segmental duplication
Sequence similarity networks
Transcriptional readthrough
title_short Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
title_full Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
title_fullStr Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
title_full_unstemmed Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
title_sort Gene fusions derived by transcriptional readthrough are driven by segmental duplication in human
dc.creator.none.fl_str_mv McCartney, Ann M.
Hyland, Edel M.
Cormican, Paul
Moran, Raymond J.
Webb, Andrew E.
Lee, Kate D.
Hernández Rodríguez, Jéssica, 1983-
Prado Martínez, Javier, 1987-
Creevey, Christopher J.
Aspden, Julie L.
McInerney, James O.
Marquès i Bonet, Tomàs, 1975-
O'Connell, Mary J.
author McCartney, Ann M.
author_facet McCartney, Ann M.
Hyland, Edel M.
Cormican, Paul
Moran, Raymond J.
Webb, Andrew E.
Lee, Kate D.
Hernández Rodríguez, Jéssica, 1983-
Prado Martínez, Javier, 1987-
Creevey, Christopher J.
Aspden, Julie L.
McInerney, James O.
Marquès i Bonet, Tomàs, 1975-
O'Connell, Mary J.
author_role author
author2 Hyland, Edel M.
Cormican, Paul
Moran, Raymond J.
Webb, Andrew E.
Lee, Kate D.
Hernández Rodríguez, Jéssica, 1983-
Prado Martínez, Javier, 1987-
Creevey, Christopher J.
Aspden, Julie L.
McInerney, James O.
Marquès i Bonet, Tomàs, 1975-
O'Connell, Mary J.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Great Ape Comparative genomics
Mechanisms of protein-coding evolution
Novel genes
Segmental duplication
Sequence similarity networks
Transcriptional readthrough
topic Great Ape Comparative genomics
Mechanisms of protein-coding evolution
Novel genes
Segmental duplication
Sequence similarity networks
Transcriptional readthrough
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/44054
http://dx.doi.org/10.1093/gbe/evz163
url http://hdl.handle.net/10230/44054
http://dx.doi.org/10.1093/gbe/evz163
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Genome Biol Evol. 2019; 11(9):2678-90
info:eu-repo/grantAgreement/ES/2PE/BFU2017-86471-P
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
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