Schuster P
1 Institut für Theoretische Chemie und Molekulare Strukturbiologie, Universität Wien, Austria.
Biol Chem. 2001 Sep;382(9):1301-14. doi: 10.1515/BC.2001.162.
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.
有关体外分子进化的理论概念和实验已发展到能够直接应用于设计具有预定特性的生物分子的阶段。体外RNA进化是发展一种全新且全面的进化模型的基础,该模型聚焦于表型及其与适应性相关的特性。基因型与表型之间的关系通过从基因型空间到表型空间的映射来描述,这种映射是多对一的,因此在基因型空间中存在扩展的中性网络所体现的中性提供了充足的空间。RNA模型将基因型 - 表型关系简化为从序列到最小自由能二级结构的映射,并允许推导其他难以获得的定量结果。进化中的连续性和不连续性通过表型空间中可及性的新概念来定义,这为直接解释RNA优化的计算机模拟提供了基础;此外,它揭示了随机基因组漂变在寻找更高适应性表型过程中的建设性作用。通过基于具有迁入的生死过程的简单随机模型,可以定量预测种群大小对进化优化过程的影响。