Harmonious genetic combinations rewire regulatory networks and flip gene essentiality
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- dc.contributor.author New, Aaron M.
- dc.contributor.author Lehner, Ben, 1978-
- dc.date.accessioned 2019-10-28T13:35:45Z
- dc.date.available 2019-10-28T13:35:45Z
- dc.date.issued 2019
- dc.description.abstract We lack an understanding of how the full range of genetic variants that occur in individuals can interact. To address this shortcoming, here we combine diverse mutations between genes in a model regulatory network, the galactose (GAL) switch of budding yeast. The effects of thousands of pairs of mutations fall into a limited number of phenotypic classes. While these effects are mostly predictable using simple rules that capture the 'stereotypical' genetic interactions of the network, some double mutants have unexpected outcomes including constituting alternative functional switches. Each of these 'harmonious' genetic combinations exhibits altered dependency on other regulatory genes. These cases illustrate how both pairwise and higher epistasis determines gene essentiality and how combinations of mutations rewire regulatory networks. Together, our results provide an overview of how broad spectra of mutations interact, how these interactions can be predicted, and how diverse genetic solutions can achieve 'wild-type' phenotypic behavior.
- dc.description.sponsorship This work was supported by a European Research Council (ERC) Consolidator grant (616434), the Spanish Ministry of Economy and Competitiveness (BFU2017–89488-P and SEV-2012–0208), the AXA Research Fund, the Bettencourt Schueller Foundation, Agencia de Gestio d’Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 1322.), and the CERCA Program/Generalitat de Catalunya. A.M. New was supported in part by fellowships from EMBO ALTF 505–2014 and the Spanish Ministry of Economy and Competitiveness Juan de la Cierva fund.
- dc.format.mimetype application/pdf
- dc.identifier.citation New AM, Lehner B. Harmonious genetic combinations rewire regulatory networks and flip gene essentiality. Nat Commun. 2019;10(1):3657. DOI: 10.1038/s41467-019-11523-z
- dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-11523-z
- dc.identifier.issn 2041-1723
- dc.identifier.uri http://hdl.handle.net/10230/42530
- dc.language.iso eng
- dc.publisher Nature Research
- dc.relation.ispartof Nature Communications. 2019;10(1):3657
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/616434
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-89488-P
- dc.rights © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Epistasis
- dc.subject.keyword Evolutionary biology
- dc.subject.keyword Genetics
- dc.subject.keyword Systems biology
- dc.title Harmonious genetic combinations rewire regulatory networks and flip gene essentiality
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion