Originally published as Genetics Published Articles Ahead of Print on February 3, 2008.

Genetics, Vol. 178, 1653-1660, March 2008, Copyright © 2008
doi:10.1534/genetics.107.085399

The Cost of Expression of Escherichia coli lac Operon Proteins Is in the Process, Not in the Products

Daniel M. Stoebel*,1, Antony M. Dean{dagger} and Daniel E. Dykhuizen*

* Department of Ecology and Evolution, Stony Brook University, Stony Brook, New York 11794 and {dagger} Department of Ecology, Evolution and Behavior and the BioTechnology Institute, University of Minnesota, St. Paul, Minnesota 55108

1 Corresponding author: Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, University of Dublin, Dublin 2, Ireland.
E-mail: daniel.stoebel{at}tcd.ie

Transcriptional regulatory networks allow bacteria to express proteins only when they are needed. Adaptive hypotheses explaining the evolution of regulatory networks assume that unneeded expression is costly and therefore decreases fitness, but the proximate cause of this cost is not clear. We show that the cost in fitness to Escherichia coli strains constitutively expressing the lactose operon when lactose is absent is associated with the process of making the lac gene products, i.e., associated with the acts of transcription and/or translation. These results reject the hypotheses that regulation exists to prevent the waste of amino acids in useless protein or the detrimental activity of unnecessary proteins. While the cost of the process of protein expression occurs in all of the environments that we tested, the expression of the lactose permease could be costly or beneficial, depending on the environment. Our results identify the basis of a single selective pressure likely acting across the entire E. coli transcriptome.