Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution.

Nature Communications
Chieh HsuAttila Becskei

Abstract

During evolution, genetic networks are rewired through strengthening or weakening their interactions to develop new regulatory schemes. In the galactose network, the GAL1/GAL3 paralogues and the GAL2 gene enhance their own expression mediated by the Gal4p transcriptional activator. The wiring strength in these feedback loops is set by the number of Gal4p binding sites. Here we show using synthetic circuits that multiplying the binding sites increases the expression of a gene under the direct control of an activator, but this enhancement is not fed back in the circuit. The feedback loops are rather activated by genes that have frequent stochastic bursts and fast RNA decay rates. In this way, rapid adaptation to galactose can be triggered even by weakly expressed genes. Our results indicate that nonlinear stochastic transcriptional responses enable feedback loops to function autonomously, or contrary to what is dictated by the strength of interactions enclosing the circuit.

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Citations

Oct 30, 2014·Nucleic Acids Research·Marie Mi BondeAttila Becskei
Oct 16, 2015·Nature·Antoine Baudrimont, Attila Becskei
Feb 4, 2014·FEMS Microbiology Reviews·Michaela ConradJohan M Thevelein
Dec 30, 2014·Trends in Biotechnology·Domitilla Del Vecchio
Oct 31, 2014·PLoS Computational Biology·Munia AminOrkun S Soyer
Aug 9, 2016·Journal of Molecular Biology·Chieh HsuAttila Becskei
Aug 29, 2016·Advanced Drug Delivery Reviews·I Cody MacDonald, Tara L Deans
Mar 24, 2017·ACS Synthetic Biology·Mumun GencogluAttila Becskei
Oct 21, 2014·Molecular BioSystems·Sarah R StockwellScott A Rifkin
Jan 31, 2017·Integrative Biology : Quantitative Biosciences From Nano to Macro·Vincent JaquetAttila Becskei
Sep 24, 2014·Nature Communications·Yolanda SchaerliMark Isalan
Sep 2, 2018·Biotechnology Journal·Venkatesh Endalur Gopinarayanan, Nikhil U Nair
Nov 14, 2017·Nature Methods·Evelina TutucciRobert H Singer
Mar 28, 2018·Nature Communications·Venkatesh Endalur Gopinarayanan, Nikhil U Nair
Sep 2, 2015·Molecular Systems Biology·Caleb GonzálezGábor Balázsi
Jan 18, 2018·Molecular Systems Biology·Magali RichardGaël Yvert
Dec 16, 2017·International Journal of Molecular Sciences·Takeo Wada, Attila Becskei
Sep 28, 2018·BMC Systems Biology·Xinyue LuoMurat Acar
Jul 15, 2017·Science Advances·Antoine BaudrimontAttila Becskei
Nov 26, 2015·Physical Biology·Imre MájerAttila Becskei
Mar 23, 2021·Frontiers in Genetics·Kholoud ShabanKrassimir Yankulov

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Methods Mentioned

BETA
PCR
flow cytometry

Software Mentioned

MATLAB

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