Letter

Nature 436, 588-592 (28 July 2005) | doi:10.1038/nature03842; Received 11 April 2005; Accepted 19 May 2005

Optimality and evolutionary tuning of the expression level of a protein

Erez Dekel1 & Uri Alon1

  1. Department of Molecular Cell Biology and Department of Physics of Complex Systems, The Weizmann Institute of Science, Rehovot 76100, Israel

Correspondence to: Uri Alon1 Correspondence and requests for materials should be addressed to U.A. (Email: urialon@weizmann.ac.il).

Different proteins have different expression levels. It is unclear to what extent these expression levels are optimized to their environment. Evolutionary theories suggest that protein expression levels maximize fitness1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, but the fitness as a function of protein level has seldom been directly measured. To address this, we studied the lac system of Escherichia coli, which allows the cell to use the sugar lactose for growth12. We experimentally measured the growth burden13, 14 due to production and maintenance of the Lac proteins (cost), as well as the growth advantage (benefit) conferred by the Lac proteins when lactose is present. The fitness function, given by the difference between the benefit and the cost, predicts that for each lactose environment there exists an optimal Lac expression level that maximizes growth rate. We then performed serial dilution evolution experiments at different lactose concentrations. In a few hundred generations, cells evolved to reach the predicted optimal expression levels. Thus, protein expression from the lac operon seems to be a solution of a cost–benefit optimization problem, and can be rapidly tuned by evolution to function optimally in new environments.

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