TY - JOUR
T1 - Evolutionary potential of transcription factors for gene regulatory rewiring
AU - Igler, Claudia
AU - Lagator, Mato
AU - Tkacik, Gasper
AU - Bollback, Jonathan P.
AU - Guet, Calin C.
N1 - Funding Information:
We thank S. Abedon, R. Grah, K. Jain, C. Nizak, T. Paixão, M. Pleska, E. Reichhart and S. Sarikas for helpful discussions. This work was supported by the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. [291734] to M.L., and European Research Council under the Horizon 2020 Framework Programme (FP/2007-2013) / ERC grant agreement no. [648440] to J.P.B. C.I. is the recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences) Fellowship of the Austrian Academy of Sciences.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
KW - Evolutionary genetics
KW - Evolvability
KW - Experimental evolution
KW - Molecular evolution
KW - Robustness
UR - https://livrepository.liverpool.ac.uk/3026254/
UR - http://www.scopus.com/inward/record.url?scp=85053529530&partnerID=8YFLogxK
UR - http://www.mendeley.com/research/evolutionary-potential-transcription-factors-gene-regulatory-rewiring
U2 - 10.1038/s41559-018-0651-y
DO - 10.1038/s41559-018-0651-y
M3 - Article
SN - 2397-334X
VL - 2
SP - 1633
EP - 1643
JO - Nature Ecology & Evolution
JF - Nature Ecology & Evolution
IS - 10
ER -