Evolution of RNA Ecologies and Functional Networks

The goal of the proposal is to study RNA-hybridization systematically and to use it as a tool to investigate coevolution. Hybridization complexes will be studied first on the level of secondary structures and later on extended by consideration of tertiary interactions. The systematic study will be based on the concept of understanding the cofolding of two RNA molecules as a mapping from the combined sequence space of both molecules into a shape space of RNA hybrids. As previously done with single RNA molecules the investigations will be performed at three levels: (i) folding all sequences of short chain length and exhaustive enumeration of structures, (ii) statistics of short derived from intermediate and long chains, and '(iii) development of a mathematical model for the mapping based on random graph theory.

Coevolution will be studied by means of a flowreactor model simulating an assay of functionally interacting RNA molecules. The computer implementation of the flowreactor model has been used already to study evolution of independently replicating RNA molecules and optimization of RNA folding. The simplest application will be template-induced and catalyzed RNA synthesis. In this case we plan also to perform full qualitative analysis of the underlying kinetic differential equations.

The model for functionally coupled organizations of ecologies of RNA molecules will be studied by computer simulation. Catalytic functions are assumed to be properties of model ribozymes. A model ribozyme has to meet both, structural conditions and sequence requirements. The catalytic activities of RNA such as template action, cleavage, ligation, and assistence in replication will be mediated through structural criteria applied to the hybridization complexes of the two cofolded molecules. Computer simulation will be complemented by a model based on a kind of metadynamics which combines stochastic and deterministic aspects of coevolution.