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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Detalles Bibliográficos
Autores: McCartney, Ann M., Hyland, Edel M., Cormican, Paul, Moran, Raymond J., Webb, Andrew E., Lee, Kate D., Hernandez Rodriguez, Jessica, Prado-Martinez, Javier|||0000-0001-5402-2721, Creevey, Christopher J., Aspden, Julie L., McInerney, James O., Marquès i Bonet, Tomàs|||0000-0002-5597-3075, O'Connell, Mary J.
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:220419
Acceso en línea:https://ddd.uab.cat/record/220419
https://dx.doi.org/urn:doi:10.1093/gbe/evz163
Access Level:acceso abierto
Palabra clave:Sequence similarity networks
Novel genes
Segmental duplication
Mechanisms of protein-coding evolution
Great Ape Comparative genomics
Transcriptional readthrough
Descripción
Sumario: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.