article published yes Claudia Igler author 46613666-F248-11E8-B48F-1D18A9856A870000-0001-7777-546X Mato Lagator author 345D25EC-F248-11E8-B48F-1D18A9856A87 Gasper Tkacik author 3D494DCA-F248-11E8-B48F-1D18A9856A870000-0002-6699-1455 Jonathan P Bollback author 2C6FA9CC-F248-11E8-B48F-1D18A9856A870000-0002-4624-4612 Calin C Guet author 47F8433E-F248-11E8-B48F-1D18A9856A870000-0001-6220-2052 CaGu department GaTk department JoBo department International IST Postdoc Fellowship Programme project Selective Barriers to Horizontal Gene Transfer project Design principles underlying genetic switch architecture project Gene regulatory networks evolve through rewiring of individual components—that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor–DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor–DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution. https://research-explorer.ista.ac.at/download/67/7830/2018_NatureEcology_Igler.pdf application/pdfno Nature Publishing Group2018 eng 00044794760002110.1038/s41559-018-0651-y 2101633 - 1643 https://research-explorer.ista.ac.at/record/5585 https://research-explorer.ista.ac.at/record/6371 C. Igler, M. Lagator, G. Tkačik, J.P. Bollback, C.C. Guet, Nature Ecology and Evolution 2 (2018) 1633–1643. Igler, C., Lagator, M., Tkačik, G., Bollback, J. P., &#38; Guet, C. C. (2018). Evolutionary potential of transcription factors for gene regulatory rewiring. <i>Nature Ecology and Evolution</i>. Nature Publishing Group. <a href="https://doi.org/10.1038/s41559-018-0651-y">https://doi.org/10.1038/s41559-018-0651-y</a> Igler, Claudia, Mato Lagator, Gašper Tkačik, Jonathan P Bollback, and Calin C Guet. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” <i>Nature Ecology and Evolution</i>. Nature Publishing Group, 2018. <a href="https://doi.org/10.1038/s41559-018-0651-y">https://doi.org/10.1038/s41559-018-0651-y</a>. C. Igler, M. Lagator, G. Tkačik, J. P. Bollback, and C. C. Guet, “Evolutionary potential of transcription factors for gene regulatory rewiring,” <i>Nature Ecology and Evolution</i>, vol. 2, no. 10. Nature Publishing Group, pp. 1633–1643, 2018. Igler, Claudia, et al. “Evolutionary Potential of Transcription Factors for Gene Regulatory Rewiring.” <i>Nature Ecology and Evolution</i>, vol. 2, no. 10, Nature Publishing Group, 2018, pp. 1633–43, doi:<a href="https://doi.org/10.1038/s41559-018-0651-y">10.1038/s41559-018-0651-y</a>. Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. 2018. Evolutionary potential of transcription factors for gene regulatory rewiring. Nature Ecology and Evolution. 2(10), 1633–1643. Igler C, Lagator M, Tkačik G, Bollback JP, Guet CC. Evolutionary potential of transcription factors for gene regulatory rewiring. <i>Nature Ecology and Evolution</i>. 2018;2(10):1633-1643. doi:<a href="https://doi.org/10.1038/s41559-018-0651-y">10.1038/s41559-018-0651-y</a> 672018-12-11T11:44:27Z2026-07-15T22:30:34Z