Evolutionary biotechnology-theory, facts and perspectives

Molecular evolution has recently been applied in biotechnology which consist of the development of evolutionary strategies in the design of biopolymers with predefined properties and functions. At the heart of this new technology are the in vitro replication and random synthesis of RNA or DNA molecules, producing large libraries of genotypes that are subjected to selection techniques following DARWIN's principle. By means of these evolutionary methods, RNA molecules were derived which specifically bind to predefined target molecules. Ribozymes with new catalytic functions were obtained as well as RNA molecules that are resistant to cleavage by specific RNases. In addition, the catalytic specificities of group I introns, a special class of ribozymes, were modified by variation and selection. Efficient applications of molecular evolution to problems in biotechnology require a fundamental and detailed understanding of the evolutionary process. Two basic questions are of primary importance: (i) How can evolutionary methods be successful as the numbers of possible genotypes are so large that the chance of obtaining a particular sequence by random processes is practically zero, and (ii) how can populations avoid being caught in evolutionary traps corresponding to local fitness optima? This review is therefore concerned with an abridged account of the theory of molecular evolution, as well as its application to biotechnology. We add a brief discussion of new techniques for the massively parallel handling and screening of very small probes as is required for the spatial separation and selection of genotypes. Finally, some imminent prospects concerning the evolutionary design of biopolymers are presented.