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Stochastic signalling rewires the interaction map of a multiple feedback network during yeast evolution
Chieh Hsu, Simone Scherrer, Antoine Buetti-Dinh, Prasuna Ratna, Julia Pizzolato, Vincent Jaquet & Attila Becskei
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Nature Communications 3, Article number: 682 doi:10.1038/ncomms1687
Received 20 July 2011 Accepted 17 January 2012 Published 21 February 2012
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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Subject terms: Biological sciences Biotechnology Evolution Microbiology
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