Dynamics of DNA methylation in recent human and great ape evolution

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  • dc.contributor.author Hernando Herráez, Irene, 1985-ca
  • dc.contributor.author Prado Martínez, Javier, 1987-ca
  • dc.contributor.author Garg, Parasca
  • dc.contributor.author Fernández Callejo, Marcosca
  • dc.contributor.author Heyn, Holgerca
  • dc.contributor.author Hvilsom, Christinaca
  • dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-ca
  • dc.contributor.author Esteller, Manelca
  • dc.contributor.author Sharp, Andrew J.ca
  • dc.contributor.author Marquès i Bonet, Tomàs, 1975-ca
  • dc.date.accessioned 2015-04-20T07:05:31Z
  • dc.date.available 2015-04-20T07:05:31Z
  • dc.date.issued 2013ca
  • dc.description.abstract DNA methylation is an epigenetic modification involved in regulatory processes such as cell differentiation during development, X-chromosome inactivation, genomic imprinting and susceptibility to complex disease. However, the dynamics of DNA methylation changes between humans and their closest relatives are still poorly understood. We performed a comparative analysis of CpG methylation patterns between 9 humans and 23 primate samples including all species of great apes (chimpanzee, bonobo, gorilla and orangutan) using Illumina Methylation450 bead arrays. Our analysis identified 800 genes with significantly altered methylation patterns among the great apes, including 170 genes with a methylation pattern unique to human. Some of these are known to be involved in developmental and neurological features, suggesting that epigenetic changes have been frequent during recent human and primate evolution. We identified a significant positive relationship between the rate of coding variation and alterations of methylation at the promoter level, indicative of co-occurrence between evolution of protein sequence and gene regulation. In contrast, and supporting the idea that many phenotypic differences between humans and great apes are not due to amino acid differences, our analysis also identified 184 genes that are perfectly conserved at protein level between human and chimpanzee, yet show significant epigenetic differences between these two species. We conclude that epigenetic alterations are an important force during primate evolution and have been under-explored in evolutionary comparative genomics.en
  • dc.description.sponsorship TMB is supported by the European Research Council (ERC Starting Grant, StG_20091118) and the Spanish Government (BFU2011-28549). AJS is supported by NIH grants 1R01DA033660, 1R01HG006696, and a grant from the Alzheimer’s Association (2012ALZNIRG69983). IHH is supported by the European Social Fund, AGAUR (Generalitat de Catalunya, Spain) and the Spanish National Research Council (CSIC). We also thank the Spanish Government for the grant BFU2009-13409-C02-02 to AN and the Barcelona Zoo (Ajuntament de Barcelona) for an award to JPM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscripten
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Hernando-Herraez I, Prado-Martinez J, Garg P, Fernandez-Callejo M, Heyn H, Hvilsom C et al. Dynamics of DNA methylation in recent human and great ape evolution. PLoS Genetics. 2013;9(9):e1003763. DOI: 10.1371/journal.pgen.1003763ca
  • dc.identifier.doi http://dx.doi.org/10.1371/journal.pgen.1003763
  • dc.identifier.issn 1553-7390ca
  • dc.identifier.uri http://hdl.handle.net/10230/23444
  • dc.language.iso engca
  • dc.publisher Public Library of Science (PLoS)ca
  • dc.relation.ispartof PLoS Genetics. 2013;9(9):e1003763
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-28549
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-13409
  • dc.rights © 2013 Hernando-Herraez et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  • dc.rights.accessRights info:eu-repo/semantics/openAccessca
  • dc.subject.other Genètica animalca
  • dc.subject.other Goril·lesca
  • dc.title Dynamics of DNA methylation in recent human and great ape evolutionen
  • dc.type info:eu-repo/semantics/articleca
  • dc.type.version info:eu-repo/semantics/publishedVersionca