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Biological processes modulating longevity across primates: a phylogenetic genome-phenome analysis

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dc.contributor.author Muntané, Gerard
dc.contributor.author Farré, Xavier
dc.contributor.author Rodríguez Pérez, Juan Antonio, 1985-
dc.contributor.author Pegueroles Queralt, Maria Cinta
dc.contributor.author Hughes, David
dc.contributor.author Magalhães, João Pedro de
dc.contributor.author Gabaldón Estevan, Juan Antonio, 1973-
dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-
dc.date.accessioned 2018-09-27T07:17:16Z
dc.date.available 2018-09-27T07:17:16Z
dc.date.issued 2018
dc.identifier.citation Muntané G, Farré X, Rodríguez JA, Pegueroles C, Hughes DA, de Magalhães JP et al. Biological processes modulating longevity across primates: a phylogenetic genome-phenome analysis. Mol Biol Evol. 2018 Aug 1;35(8):1990-2004. DOI: 10.1093/molbev/msy105
dc.identifier.issn 0737-4038
dc.identifier.uri http://hdl.handle.net/10230/35510
dc.description.abstract Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan across primate species. We used two different approaches. First, we searched for parallel amino-acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino-acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as wound healing, blood coagulation, and cardiovascular disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the antagonistic pleiotropy theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the phylogenetic generalized least squares, we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling, and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity.
dc.description.sponsorship This work was supported by Ministerio de Ciencia e Innovación, Spain (BFU2012-38236 and BFU2015-68649-P (MINECO/FEDER, UE) to AN), by Direcció General de Recerca, Generalitat de Catalunya (2014SGR1311 and 2014SGR866 to A.N., and 2014BP-B00157 to G.M.), by the Spanish National Institute of Bioinfomatics of the Instituto de Salud Carlos III (PT13/0001/0026), by “Unidad de Excelencia María de Maeztu”, funded by the MINECO (ref: MDM-2014-0370), and by FEDER (Fondo Europeo de Desarrollo Regional)/FSE (Fondo Social Europeo)
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof Molecular Biology and Evolution. 2018 Aug 1;35(8):1990-2004
dc.rights © Gerard Muntané, Xavier Farré, Juan Antonio Rodríguez el al 2018. Published by Oxford University Press. This is an Open Access article distributed under the terms of a Creative Commons Attribution License
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.subject.other Evolució (Biologia)
dc.subject.other Longevitat
dc.subject.other Primats
dc.subject.other Genètica
dc.subject.other Envelliment
dc.title Biological processes modulating longevity across primates: a phylogenetic genome-phenome analysis
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1093/molbev/msy105
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-38236
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-68649-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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