Optimality and evolutionary tuning of the expression level of a protein

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Abstract

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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Figure 1: The lac operon of E. coli and the experimental design in the present study.
Figure 2: Cost and benefit functions of lac expression in wild-type E. coli.
Figure 3: 3 Predicted relative growth rate of cells (the fitness function) as a function of Lac protein expression.
Figure 4: Experimental evolutionary adaptation of E. coli cells to different concentrations of lactose.

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Acknowledgements

We thank M. Elowitz, R. Kishony, G. Sela, B. Shraiman and all members of our laboratory for discussions. We thank the NIH, ISF and Minerva for support. E.D. thanks the Clore postdoctoral fellowship for support.

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Correspondence to Uri Alon.

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Supplementary Data

This details additional data on the experiments and calculation presented in the main text. It also contains Supplementary Figure S1-S8 and Supplementary Tables S1 and S2. (PDF 239 kb)

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Dekel, E., Alon, U. Optimality and evolutionary tuning of the expression level of a protein. Nature 436, 588–592 (2005) doi:10.1038/nature03842

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