Molecular evolution: A theory approaches experiments

Applied Molecular evolution, especially in vitro techniques developed in the last few years have revolutionized the design of functional biopolymers. SELEX techniques for example have become particularly popular. These methods have been enormously successful, yet this success is not trivial: the huge number of sequences being searched, the low concentrations of individual species and the bias and noise inherent in the techniques would seem to make these experiments very difficult. The theory presented here will give a comprehensive description of directed molecular evolution of RNA molecules in detail and biopolymers in general. Essential for an understanding is an adequate genotype-phenotype relationship. This relationship exhibits neutral properties which explain the success of these experimental methods. Influences of the initial library, the error rate, the cycle length and other parameters on the experiments are characterized. New problems arise in extending the concept of evolutionary optimization of biopolymers in a Darwinian scenario to complex reaction networks. (C) 1998 Elsevier Science B.V. All rights reserved.