The Molecular Clock in the Evolution of Protein Structures

The molecular clock hypothesis, which states that substitutions accumulate in protein sequences at a constant rate, plays a fundamental role in molecular evolution but it is violated when selective or mutational processes vary with time. Such violations of the molecular clock have been widely invest...

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Detalles Bibliográficos
Autores: Pascual-García, Alberto, Arenas, Miguel, Bastolla, Ugo
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/374558
Acceso en línea:http://hdl.handle.net/10261/374558
https://api.elsevier.com/content/abstract/scopus_id/85073668537
Access Level:acceso abierto
Palabra clave:Co-evolution
Molecular clock
Protein structure evolution
Selection
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spelling The Molecular Clock in the Evolution of Protein StructuresPascual-García, AlbertoArenas, MiguelBastolla, UgoCo-evolutionMolecular clockProtein structure evolutionSelectionThe molecular clock hypothesis, which states that substitutions accumulate in protein sequences at a constant rate, plays a fundamental role in molecular evolution but it is violated when selective or mutational processes vary with time. Such violations of the molecular clock have been widely investigated for protein sequences, but not yet for protein structures. Here, we introduce a novel statistical test (Significant Clock Violations) and perform a large scale assessment of the molecular clock in the evolution of both protein sequences and structures in three large superfamilies. After validating our method with computer simulations, we find that clock violations are generally consistent in sequence and structure evolution, but they tend to be larger and more significant in structure evolution. Moreover, changes of function assessed through Gene Ontology and InterPro terms are associated with large and significant clock violations in structure evolution. We found that almost one third of significant clock violations are significant in structure evolution but not in sequence evolution, highlighting the advantage to use structure information for assessing accelerated evolution and gathering hints of positive selection. Clock violations between closely related pairs are frequently significant in sequence evolution, consistent with the observed time dependence of the substitution rate attributed to segregation of neutral and slightly deleterious polymorphisms, but not in structure evolution, suggesting that these substitutions do not affect protein structure although they may affect stability. These results are consistent with the view that natural selection, both negative and positive, constrains more strongly protein structures than protein sequences. Our code for computing clock violations is freely available at https://github.com/ugobas/Molecular_clock.This work has been funded by the Spanish Ministry of Science [BIO2016-79043-P and BFU2012-40020]; the Spanish Government [RYC-2015-18241] and the Xunta de Galiciaž [ED431F 2018/08] to M.A.; the Simons Foundation [542381 to A.P.G., in part].Peer reviewedOxford University PressMinisterio de Economía y Competitividad (España)Xunta de GaliciaSimons FoundationPascual-García, Alberto [0000-0002-8444-3196]Arenas, Miguel [0000-0002-0516-2717]Bastolla, Ugo [0000-0001-9342-4678]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://hdl.handle.net/10261/374558https://api.elsevier.com/content/abstract/scopus_id/85073668537reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//BIO2016-79043-Pinfo:eu-repo/grantAgreement/MINECO//RYC-2015-18241https://doi.org/10.1093/sysbio/syz022Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3745582026-05-22T06:33:51Z
dc.title.none.fl_str_mv The Molecular Clock in the Evolution of Protein Structures
title The Molecular Clock in the Evolution of Protein Structures
spellingShingle The Molecular Clock in the Evolution of Protein Structures
Pascual-García, Alberto
Co-evolution
Molecular clock
Protein structure evolution
Selection
title_short The Molecular Clock in the Evolution of Protein Structures
title_full The Molecular Clock in the Evolution of Protein Structures
title_fullStr The Molecular Clock in the Evolution of Protein Structures
title_full_unstemmed The Molecular Clock in the Evolution of Protein Structures
title_sort The Molecular Clock in the Evolution of Protein Structures
dc.creator.none.fl_str_mv Pascual-García, Alberto
Arenas, Miguel
Bastolla, Ugo
author Pascual-García, Alberto
author_facet Pascual-García, Alberto
Arenas, Miguel
Bastolla, Ugo
author_role author
author2 Arenas, Miguel
Bastolla, Ugo
author2_role author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Xunta de Galicia
Simons Foundation
Pascual-García, Alberto [0000-0002-8444-3196]
Arenas, Miguel [0000-0002-0516-2717]
Bastolla, Ugo [0000-0001-9342-4678]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Co-evolution
Molecular clock
Protein structure evolution
Selection
topic Co-evolution
Molecular clock
Protein structure evolution
Selection
description The molecular clock hypothesis, which states that substitutions accumulate in protein sequences at a constant rate, plays a fundamental role in molecular evolution but it is violated when selective or mutational processes vary with time. Such violations of the molecular clock have been widely investigated for protein sequences, but not yet for protein structures. Here, we introduce a novel statistical test (Significant Clock Violations) and perform a large scale assessment of the molecular clock in the evolution of both protein sequences and structures in three large superfamilies. After validating our method with computer simulations, we find that clock violations are generally consistent in sequence and structure evolution, but they tend to be larger and more significant in structure evolution. Moreover, changes of function assessed through Gene Ontology and InterPro terms are associated with large and significant clock violations in structure evolution. We found that almost one third of significant clock violations are significant in structure evolution but not in sequence evolution, highlighting the advantage to use structure information for assessing accelerated evolution and gathering hints of positive selection. Clock violations between closely related pairs are frequently significant in sequence evolution, consistent with the observed time dependence of the substitution rate attributed to segregation of neutral and slightly deleterious polymorphisms, but not in structure evolution, suggesting that these substitutions do not affect protein structure although they may affect stability. These results are consistent with the view that natural selection, both negative and positive, constrains more strongly protein structures than protein sequences. Our code for computing clock violations is freely available at https://github.com/ugobas/Molecular_clock.
publishDate 2019
dc.date.none.fl_str_mv 2019
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/374558
https://api.elsevier.com/content/abstract/scopus_id/85073668537
url http://hdl.handle.net/10261/374558
https://api.elsevier.com/content/abstract/scopus_id/85073668537
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//BIO2016-79043-P
info:eu-repo/grantAgreement/MINECO//RYC-2015-18241
https://doi.org/10.1093/sysbio/syz022
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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