The physical basis and practical consequences of biological promiscuity.

Proteins interact with metabolites, nucleic acids, and other proteins to orchestrate the myriad catalytic, structural and regulatory functions that support life from the simplest microbes to the most complex multicellular organisms. These molecular interactions are often exquisitely specific, but never perfectly so. Adventitious "promiscuous" interactions are ubiquitous due to the thousands of macromolecules and small molecules crowded together in cells. Such interactions may perturb protein function at the molecular level, but as long as they do not compromise organismal fitness, they will not be removed by natural selection. Although promiscuous interactions are physiologically irrelevant, they are important because they can provide a vast reservoir of potential functions that can provide the starting point for evolution of new functions, both in nature and in the laboratory.