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Robustness and innovation in synthetic genotype networks

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dc.contributor.author Santos-Moreno, Javier
dc.contributor.author Tasiudi, Eve
dc.contributor.author Kusumawardhani, Hadiastri
dc.contributor.author Stelling, Joerg
dc.contributor.author Schaerli, Yolanda
dc.date.accessioned 2023-09-21T07:01:43Z
dc.date.available 2023-09-21T07:01:43Z
dc.date.issued 2023
dc.identifier.citation Santos-Moreno J, Tasiudi E, Kusumawardhani H, Stelling J, Schaerli Y. Robustness and innovation in synthetic genotype networks. Nat Commun. 2023;14:2454. DOI: 10.1038/s41467-023-38033-3
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/57933
dc.description.abstract Genotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. They facilitate evolutionary innovation by enabling the exploration of different neighborhoods in genotype space. Genotype networks, first suggested by theoretical models, have been empirically confirmed for proteins and RNAs. Comparative studies also support their existence for gene regulatory networks (GRNs), but direct experimental evidence is lacking. Here, we report the construction of three interconnected genotype networks of synthetic GRNs producing three distinct phenotypes in Escherichia coli. Our synthetic GRNs contain three nodes regulating each other by CRISPR interference and governing the expression of fluorescent reporters. The genotype networks, composed of over twenty different synthetic GRNs, provide robustness in face of mutations while enabling transitions to innovative phenotypes. Through realistic mathematical modeling, we quantify robustness and evolvability for the complete genotype-phenotype map and link these features mechanistically to GRN motifs. Our work thereby exemplifies how GRN evolution along genotype networks might be driving evolutionary innovation.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2023;14:2454
dc.rights © The Author(s) 2023. 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.uri http://creativecommons.org/licenses/by/4.0/
dc.title Robustness and innovation in synthetic genotype networks
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41467-023-38033-3
dc.subject.keyword Evolvability
dc.subject.keyword Regulatory networks
dc.subject.keyword Robustness
dc.subject.keyword Synthetic biology
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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