The complete local genotype-phenotype landscape for the alternative splicing of a human exon

The properties of genotype-phenotype landscapes are crucial for understanding evolution but are not characterized for most traits. Here, we present a >95% complete local landscape for a defined molecular function-the alternative splicing of a human exon (FAS/CD95 exon 6, involved in the contr...

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Detalles Bibliográficos
Autores: Julien, Philippe, Miñana Gómez, Belén, Baeza Centurión, Pablo, 1989-, Valcárcel, J. (Juan), Lehner, Ben, 1978-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
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:10230/26794
Acceso en línea:http://hdl.handle.net/10230/26794
http://dx.doi.org/10.1038/ncomms11558
Access Level:acceso abierto
Palabra clave:Exons
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spelling The complete local genotype-phenotype landscape for the alternative splicing of a human exonJulien, PhilippeMiñana Gómez, BelénBaeza Centurión, Pablo, 1989-Valcárcel, J. (Juan)Lehner, Ben, 1978-ExonsThe properties of genotype-phenotype landscapes are crucial for understanding evolution but are not characterized for most traits. Here, we present a >95% complete local landscape for a defined molecular function-the alternative splicing of a human exon (FAS/CD95 exon 6, involved in the control of apoptosis). The landscape provides important mechanistic insights, revealing that regulatory information is dispersed throughout nearly every nucleotide in an exon, that the exon is more robust to the effects of mutations than its immediate neighbours in genotype space, and that high mutation sensitivity (evolvability) will drive the rapid divergence of alternative splicing between species unless it is constrained by selection. Moreover, the extensive epistasis in the landscape predicts that exonic regulatory sequences may diverge between species even when exon inclusion levels are functionally important and conserved by selection.Work in B.L.’s lab was supported by the European Research Council (Consolidator grant IR-DC, 616434), the Spanish Ministry of Economy and Competitiveness (MICINN, BFU2011-26206), the AXA Research Fund, FP7 Project 4DCellFate (277899), Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) and the EMBL-CRG Systems Biology Program. Work in J.V.’s lab was supported by Fundación Botín, by Banco de Santander through its Santander Universities Global Division and by Consolider RNAREG, MICINN and AGAUR. P.J. was supported by an EMBO long-term fellowship.Nature Publishing Group201620162016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/26794http://dx.doi.org/10.1038/ncomms11558reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésNature communications. 2016; 7: 11558info:eu-repo/grantAgreement/ES/3PN/BFU2011-26206info:eu-repo/grantAgreement/EC/FP7/277899info:eu-repo/grantAgreement/EC/FP7/277899© Nature Publishing Group. http://www.nature.com/ncomms/2016/160510/ncomms11558/pdf/ncomms11558.pdf/nThis work is licensed under a Creative Commons Attribution 4.0 International Licensehttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/267942026-05-29T05:05:01Z
dc.title.none.fl_str_mv The complete local genotype-phenotype landscape for the alternative splicing of a human exon
title The complete local genotype-phenotype landscape for the alternative splicing of a human exon
spellingShingle The complete local genotype-phenotype landscape for the alternative splicing of a human exon
Julien, Philippe
Exons
title_short The complete local genotype-phenotype landscape for the alternative splicing of a human exon
title_full The complete local genotype-phenotype landscape for the alternative splicing of a human exon
title_fullStr The complete local genotype-phenotype landscape for the alternative splicing of a human exon
title_full_unstemmed The complete local genotype-phenotype landscape for the alternative splicing of a human exon
title_sort The complete local genotype-phenotype landscape for the alternative splicing of a human exon
dc.creator.none.fl_str_mv Julien, Philippe
Miñana Gómez, Belén
Baeza Centurión, Pablo, 1989-
Valcárcel, J. (Juan)
Lehner, Ben, 1978-
author Julien, Philippe
author_facet Julien, Philippe
Miñana Gómez, Belén
Baeza Centurión, Pablo, 1989-
Valcárcel, J. (Juan)
Lehner, Ben, 1978-
author_role author
author2 Miñana Gómez, Belén
Baeza Centurión, Pablo, 1989-
Valcárcel, J. (Juan)
Lehner, Ben, 1978-
author2_role author
author
author
author
dc.subject.none.fl_str_mv Exons
topic Exons
description The properties of genotype-phenotype landscapes are crucial for understanding evolution but are not characterized for most traits. Here, we present a >95% complete local landscape for a defined molecular function-the alternative splicing of a human exon (FAS/CD95 exon 6, involved in the control of apoptosis). The landscape provides important mechanistic insights, revealing that regulatory information is dispersed throughout nearly every nucleotide in an exon, that the exon is more robust to the effects of mutations than its immediate neighbours in genotype space, and that high mutation sensitivity (evolvability) will drive the rapid divergence of alternative splicing between species unless it is constrained by selection. Moreover, the extensive epistasis in the landscape predicts that exonic regulatory sequences may diverge between species even when exon inclusion levels are functionally important and conserved by selection.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016
2016
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/10230/26794
http://dx.doi.org/10.1038/ncomms11558
url http://hdl.handle.net/10230/26794
http://dx.doi.org/10.1038/ncomms11558
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nature communications. 2016; 7: 11558
info:eu-repo/grantAgreement/ES/3PN/BFU2011-26206
info:eu-repo/grantAgreement/EC/FP7/277899
info:eu-repo/grantAgreement/EC/FP7/277899
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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
repository.name.fl_str_mv
repository.mail.fl_str_mv
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