Design principles for elementary gene circuits: Elements, methods, and examples

The control of gene expression involves complex circuits that exhibit enorm ous variation in design. For years the most convenient explanation for thes e variations was historical accident. According to this view, evolution is a haphazard process in which many different designs are generated by chance ; there are many ways to accomplish the same thing, and so no further meani ng can be attached to such different but equivalent designs. In recent year s a more satisfying explanation based on design principles has been found f or at least certain aspects of gene circuitry. By design principle we mean a rule that characterizes some biological feature exhibited by a class of s ystems such that discovery of the rule allows one not only to understand kn own instances but also to predict new instances within the class. The centr al importance of gene regulation in modern molecular biology provides stron g motivation to search for more of these underlying design principles. The search is in its infancy and there are undoubtedly many design principles t hat remain to be discovered. The focus of this three-part review will be th e class of elementary gene circuits in bacteria. The first part reviews sev eral elements of design that enter into the characterization of elementary gene circuits in prokaryotic organisms. Each of these elements exhibits a v ariety of realizations whose meaning is generally unclear. The second part reviews mathematical methods used to represent, analyze, and compare altern ative designs. Emphasis is placed on particular methods that have been used successfully to identify design principles for elementary gene circuits. T he third part reviews four design principles that make specific predictions regarding (1) two alternative modes of gene control, (2) three patterns of coupling gene expression in elementary circuits, (3) two types of switches in inducible gene circuits, and (4) the realizability of alternative gene circuits and their response to phased environmental cues. In each case, the predictions are supported by experimental evidence. These results are impo rtant for understanding the function, design, and evolution of elementary g ene circuits. (C) 2001 American Institute of Physics.