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Biophys. J. BioFAST: First Published July 28, 2006. doi:10.1529/biophysj.105.077420
© 2006 by the Biophysical Society.


A more recent version of this article appeared on October 15, 2006.
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BIOPHYSICAL THEORY AND MODELING

In silico evolved lac operons exhibit bistability for artificial inducers, but not for lactose

Milan van Hoek 1* and Paulien Hogeweg 1

1 Utrecht University

* To whom correspondence should be addressed. E-mail: m.j.a.vanhoek{at}bio.uu.nl.

Submitted on November 8, 2005
Revised on January 31, 2006
Accepted on 11 July 2006


   Abstract
Bistability in the lac operon of Escherichia coli has been widely studied, both experimentally and theoretically. Experimentally, bistability has been observed when Escherichia coli is induced by an artificial, non-metabolizable, inducer. However, if the lac operon is induced with lactose, the natural inducer, bistability has not been demonstrated. We derive an analytical expression which can predict the occurrence of bistability both for artificial inducers and lactose. We find very different conditions for bistability in the two cases. Indeed, for artificial inducers bistability is predicted, but for lactose the condition for bistability is much more difficult to satisfy. Moreover we demonstrate that in silico evolution of the lac operon generates an operon that avoids bistability with respect to lactose, but does exhibit bistability with respect to artificial inducers. Indeed the activity of this evolved operon strikingly resembles the experimentally observed activity of the operon. Thus our computational experiments suggest that the wild-type lac operon, which regulates lactose metabolism, is not a bistable switch. Nevertheless, for engineering purposes, this operon can be used as a bistable switch with artificial inducers.

Key Words: analytical model, computational model, evolution, gene regulation, genetic switch, hysteresis




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Copyright © 2006 by the Biophysical Society.