Evolution in silico and in vitro: the RNA model

Theoretical concepts and experiments dealing with the evolution of molecules in vitro reached a state that allows for direct applications to the design of biomolecules with predefined properties. RNA evolution in vitro represents a basis for the development of a new and comprehensive model of evolution, focusing on the phenotype and its fitness relevant properties. Relations between genotypes and phenotypes are described by mappings from genotype space onto a space of phenotypes, which are many-to-one and thus give ample room for neutrality as expressed by the existence of extended neutral networks in genotype space. The RNA model reduces genotype-phenotype relations to mappings from sequences into secondary structures of minimal free energies and allows for derivation of otherwise inaccessible quantitative results. Continuity and discontinuity in evolution are defined through a new notion of accessibility in phenotype space that provides a basis for straight forward interpretation of computer simulations on RNA optimization; furthermore, it reveals the constructive role of random genomic drift in the search for phenotypes of higher fitness. The effects of population size on the course of evolutionary optimization can be predicted quantitatively by means of a simple stochastic model based on a birth-anddeath process with immigration.