Evolution of RNA Structure

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

Evolutionary patterns and processes are imprinted in the three-dimensional (3D) structure of nucleic acid molecules. In this project, an approach that embeds structure and function directly into phylogenetic analysis is used to search for these patterns and processes in the structure of several functional RNA. Structural features are treated as ordered multi-state cladistic characters, and the transformation from one character state to another is 'polarized' by invoking an evolutionary tendency towards molecular order. This novel approach allows reconstruction of evolutionary histories directly from topological, thermodynamic and statistical features in molecules. This makes possible a 'direct' evolutionary tracing of functional properties linked to structural characteristics. The project addresses basic questions such as the origin and diversification of life and the genetic code, and the role of lateral gene transfer in evolution. Its ultimate goal is the identification of processes driving the evolution of RNA structure. Specific objectives include (1) phylogenetic analysis of RNA at different evolutionary levels in molecules such as transfer (tRNA) and ribosomal RNA (rRNA); (2) evolutionary tracing of geometric and statistical characters describing functional and statistical mechanical properties; (3) phylogenomic analysis of RNA structure using a molecular morphospace that describes the architecture and biophysics of RNA at a universal level; and (4) development of evolutionary models inferred from patterns of character change. The goal of the project is to establish direct evolutionary links between structure and function in macromolecules, focusing on RNA. This knowledge should provide manifold benefits for the biological sciences. RNA molecules are important catalysts and play crucial roles in cellular processes, such as the modulation of gene expression by noncoding RNA molecules, the translational tagging of proteins, and the targeted degradation of mRNA. RNA structure is also crucial for sequence selection in antisense targeting applications. Understanding the evolution of RNA will ultimately help investigators to understand the history of our natural world and to address issues concerning its future.