Lactose isn't present in our guts all the time. To ingest it and other occasional sources of nutrition, Escherichia coli (see figure) must detect the molecules and then make the proteins that help harvest them. That process of on-demand protein production is called gene regulation. It's the subject of a new quantitative analysis by physicists Ulrich Gerland of the University of Munich, Germany and Terence Hwa of the University of California, San Diego. E. coli uses two modes of gene regulation. In (+ +) control, proteins called transcription factors float freely in the cell. When a TF molecule meets its molecular target--lactose, say--it locks onto the appropriate region of the bacterium's DNA and triggers the production of the appropriate protein. In (− −) control, the TF is usually bound to the DNA and blocks protein production until TF's molecular target arrives to detach the TF and lift the block. Both modes are equally effective. When does evolution favor one over the other? The answer, according to Gerland and Hwa, depends on a tug of war between two competing selection principles. The use-it-or-lose-it principle favors (+ +) control during feasts and (− −) control during famines, whereas the wear-and-tear principle favors the opposite. Both selection principles mitigate the adverse effects of genetic mutation but, as Gerland and Hwa found, whether one prevails over the other depends on the size and age of the colony and on how rapidly the food supply fluctuates. Besides quantifying gene regulation, Gerland and Hwa's analysis might help pharmacologists understand and combat the resistance of bacteria to antibiotics. One strain of E. coli, called mar, is resistant to tetracycline, an otherwise potent antibiotic, due to the working of two transcription factors. (U. Gerland, T. Hwa, Proc. Natl. Acad. Sci. USA 106, 8841, 2009.) —Charles Day
