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Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution

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dc.contributor.author Schaerli, Yolanda
dc.contributor.author Jiménez, Alba
dc.contributor.author Duarte, José M.
dc.contributor.author Mihajlovic, Ljiljana
dc.contributor.author Renggli, Julien
dc.contributor.author Isalan, Mark
dc.contributor.author Sharpe, James
dc.contributor.author Wagner, Andreas
dc.date.accessioned 2019-11-22T08:54:24Z
dc.date.available 2019-11-22T08:54:24Z
dc.date.issued 2018
dc.identifier.citation Schaerli Y, Jiménez A, Duarte JM, Mihajlovic L, Renggli J, Isalan M, Sharpe J, Wagner A. Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution. Mol Syst Biol. 2018; 14(9):e8102. DOI 10.15252/msb.20178102
dc.identifier.issn 1744-4292
dc.identifier.uri http://hdl.handle.net/10230/42935
dc.description.abstract Phenotypic variation is the raw material of adaptive Darwinian evolution. The phenotypic variation found in organismal development is biased towards certain phenotypes, but the molecular mechanisms behind such biases are still poorly understood. Gene regulatory networks have been proposed as one cause of constrained phenotypic variation. However, most pertinent evidence is theoretical rather than experimental. Here, we study evolutionary biases in two synthetic gene regulatory circuits expressed in Escherichia coli that produce a gene expression stripe-a pivotal pattern in embryonic development. The two parental circuits produce the same phenotype, but create it through different regulatory mechanisms. We show that mutations cause distinct novel phenotypes in the two networks and use a combination of experimental measurements, mathematical modelling and DNA sequencing to understand why mutations bring forth only some but not other novel gene expression phenotypes. Our results reveal that the regulatory mechanisms of networks restrict the possible phenotypic variation upon mutation. Consequently, seemingly equivalent networks can indeed be distinct in how they constrain the outcome of further evolution.
dc.description.sponsorship We thank Elke Karaus Wyer for carrying out preliminary experiments and Joshua L. Payne for critical reading. We thank the Sanger Sequencing team from Microsynth for their support. YS, JMD and LM acknowledge support by the Swiss National Science Foundation (PZ00P3‐148235 and 31003A_175608 to YS); AW acknowledges support by Swiss National Science Foundation grant 31003A_146137, by ERC Advanced Grant 739874, by an EpiphysX RTD grant from SystemsX.ch and by the University Priority Research Program in Evolutionary Biology at the University of Zurich. MI is funded by a Wellcome Trust UK New Investigator Award (WT102944) and by the Volkswagen Foundation. AJ and JS acknowledge the Spanish Ministry of Economy, Industry and Competitiveness (MINECO), BFU2010‐16428, the European Union's Horizon 2020 research and innovation program under Grant Agreement No. 670555, the European Union Seventh Framework Program (FP7/2007‐2013) under grant agreement 601062; the Spanish Ministry of Economy, Industry and Competitiveness “Centro de Excelencia Severo Ochoa 2013–2017”, SEV‐2012‐0208 and the Cerca Programme/Generalitat de Catalunya.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley-Blackwell
dc.relation.ispartof Mol Syst Biol. 2018; 14(9):e8102
dc.rights 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution 4.0 License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Synthetic circuits reveal how mechanisms of gene regulatory networks constrain evolution
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.15252/msb.20178102
dc.subject.keyword Constrained evolution
dc.subject.keyword Epistasis
dc.subject.keyword Gene regulatory networks
dc.subject.keyword Regulatory mechanisms
dc.subject.keyword Synthetic circuits
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/739874
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2010‐16428
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/670555
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/601062
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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