Evolutionary potential of transcription factors for gene regulatory rewiring

Igler, Claudia, Lagator, Mato, Tkačik, Gasper, Bollback, Jonathan P ORCID: 0000-0002-4624-4612 and Guet, Calin C
(2018) Evolutionary potential of transcription factors for gene regulatory rewiring. NATURE ECOLOGY & EVOLUTION, 2 (10). pp. 1633-1643.

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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.

Item Type: Article
Uncontrolled Keywords: Evolutionary genetics, Evolvability, Experimental evolution, Molecular evolution, Robustness
Depositing User: Symplectic Admin
Date Deposited: 14 Sep 2018 08:46
Last Modified: 19 Jan 2023 01:17
DOI: 10.1038/s41559-018-0651-y
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3026254