Evolution of RNA Structure and Origins of Modern Chemistry

University Of Illinois At Urbana-Champaign, Urbana IL

Investigators

Abstract

Evolutionary patterns and processes are imprinted in the 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 non-protein coding RNA (ncRNA). Structural features are treated as ordered multi-state phylogenetic characters, and the transformation from one character state to another 'polarized' by invoking an evolutionary tendency towards molecular order. In an effort at synthesis, the approach is here used to integrate the information found in RNA structure with that in the phylogenomics of protein architecture, exploring the evolution of the protein biosynthetic machinery in light of other cellular processes. The project provides global evolutionary views of ncRNA at the structural and substructural levels and explores the origins of modern biochemistry. Major objectives include the following: (1) Global analysis of ncRNA structure: A molecular morphospace that describes the architecture and biophysics of RNA at global level is used to compare different classes of ncRNA molecules (from small RNA to large RNA ensembles) and produce pan-molecular phylogenies of structure. These phylogenies generate timelines of molecular diversification and tools for evolutionary classification. (2) Global analysis of ncRNA substructures: Phylogenetic trees of molecular substructures in molecules and molecular repertoires are generated together with evolutionary heat maps that map ancestries onto two- and three-dimensional molecular representations. The approach establishes evolutionary origins for the structures of ncRNAs examined and relative timelines of substructural diversification in molecules, molecular ensembles, and the evolved ncRNA world. (3) Models of structural evolution for ncRNAs: Matrices of character transformation costs and models of evolution defined by trees of substructures are used to reveal processes driving the evolution of RNA structure. (4) Synthesis of knowledge derived from RNA structure and protein architecture: Phylogenetic information embedded in trees of RNA molecules and substructures are integrated with phylogenomic information in trees of protein folds, fold superfamilies, and domain combinations. Timelines of protein and ncRNA evolution are linked to timelines of general biological processes. (5) Evolution of the protein biosynthetic machinery: The generation of trees of molecules and substructures is coupled to phylogenetic constraint analyses and interaction maps that compare evolution of functional substructures in different molecules, revealing diversification patterns and structural co-variation in components of the translation machinery. Synthesis is an essential component of scientific inquiry. This project is novel and integrates research related to the evolution of the modern protein and RNA worlds using molecular survey, history reconstruction, and computational analysis. It also provides a unique and phylogenetically-deep view of biology. Linking macromolecular structure and function is key to understanding cellular functions and how these evolve. This knowledge provides manifold benefits. RNA molecules are important catalysts and play crucial roles in cellular processes. They are, for example, used in RNA interference and antisense targeting applications that are economically important. However, the expanding repertoire of known functional RNA demands efforts to catalogue and classify RNA structures comparable to those in proteins. Finally, translational research is needed to interpret the fruits of functional and structural genomics. Evolutionary bioinformatics offers here unprecedented opportunities to address fundamental issues in the history of our natural world. Insights from the project are shared with the community through scientific meetings and short workshops. In addition, the research benefits society by providing unique educational opportunities, including research participation by undergraduate students belonging to groups underrepresented in science and the involvement of middle school teachers in the development of educational tools and other activities.