Epigenetic epistatic interactions constrain the evolution of gene expression

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  • dc.contributor.author Park, Solip
  • dc.contributor.author Lehner, Ben, 1978-
  • dc.date.accessioned 2024-10-21T06:20:34Z
  • dc.date.available 2024-10-21T06:20:34Z
  • dc.date.issued 2013
  • dc.description.abstract Reduced activity of two genes in combination often has a more detrimental effect than expected. Such epistatic interactions not only occur when genes are mutated but also due to variation in gene expression, including among isogenic individuals in a controlled environment. We hypothesized that these ‘epigenetic’ epistatic interactions could place important constraints on the evolution of gene expression. Consistent with this, we show here that yeast genes with many epistatic interaction partners typically show low expression variation among isogenic individuals and low variation across different conditions. In addition, their expression tends to remain stable in response to the accumulation of mutations and only diverges slowly between strains and species. Yeast promoter architectures, the retention of gene duplicates, and the divergence of expression between humans and chimps are also consistent with selective pressure to reduce the likelihood of harmful epigenetic epistatic interactions. Based on these and previous analyses, we propose that the tight regulation of epistatic interaction network hubs makes an important contribution to the maintenance of a robust, ‘canalized’ phenotype. Moreover, that epigenetic epistatic interactions may contribute substantially to fitness defects when single genes are deleted.
  • dc.description.sponsorship We thank JS Yang, J Semple and A Burga for helpful discussions, Itay Tirosh for sharing ED data of human genes. This work was funded by the European Research Council (ERC), MINECO Plan Nacional grants BFU2008‐00365 and BFU2011‐26206, ERASysBio+ ERANET project EUI2009‐04059 GRAPPLE, the European Molecular Biology Organization (EMBO) Young Investigator Program, EU Framework 7 project 277899 4DCellFate, and the EMBL/CRG Systems Biology Program.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Park S, Lehner B. Epigenetic epistatic interactions constrain the evolution of gene expression. Molecular Systems Biology. 2013 Jan;9(1):645. DOI: 10.1038/msb.2013.2
  • dc.identifier.doi http://dx.doi.org/10.1038/msb.2013.2
  • dc.identifier.issn 1744-4292
  • dc.identifier.uri http://hdl.handle.net/10230/68242
  • dc.language.iso eng
  • dc.publisher EMBO Press
  • dc.relation.ispartof Molecular Systems Biology. 2013 Jan;9(1):645
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/277899
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2008‐00365
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011‐26206
  • dc.rights Copyright © 2013 EMBO and Macmillan Publishers Limited. This is an open‐access article distributed under the terms of the Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-sa/3.0/
  • dc.subject.keyword Epigenetics
  • dc.subject.keyword Epistasis
  • dc.subject.keyword Evolution
  • dc.subject.keyword Gene expression
  • dc.subject.keyword Genetic interaction
  • dc.title Epigenetic epistatic interactions constrain the evolution of gene expression
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion