RNA as an Interface to the Environment: From Ancient to Modern Ciliate RNAs

Abstract

The RNA world hypothesis [23] proposes that early life once relied on RNA as both its central informational and catalytic macromolecule. In order for RNA to truly stand on its own prior to the evolution of DNA and proteins, it would also have to have a robust capability to sense and respond to environmental change. RNA's complex folds require divalent cations for stability and often catalysis; Mg2+ and Ca2+ are two of the most prevalent ions in Earth's oceans and have a dynamic interplay with RNA structure. In this thesis I use Tetrahymena thermophila's catalytic group I intron [34] as a model system to both quantify how this ribozyme displays a dynamic fitness to Mg2+ and Ca2+ and I further mathematically model this phenomenon, displaying how a ribozyme's strategy of cation use confers evolutionary fitness in the context of ancient life. RNA's ability to respond to environmental change is further corroborated by its prominence as a regulatory element in modern life. In the final section of this thesis I seek to uncover novel functional RNA motifs that may regulate gene expression in Oxytricha trifallax. The overarching aim is to examine the RNA world hypothesis by testing RNA's versatility in the context of the early Earth's chemistry as well as in the context of a complex modern genome.