(Georgia Institute of Technology, 2022-05-02)
Haynes, Jay William
Translation and the ribosome are universal and necessary components of biology. Testing the predictions of models that detail the evolution of translation and the ribosome can provide us with a fundamental understanding of the nature of life processes. This dissertation discusses work focused on some predictions based in evolutionary models and the tools used to test predictions.
We develop a software tool for processing of melting data. This tool allows the user to see the effects of adjusting processing parameters in real time. Aims of this tool include aiding the experimentalist by shortening data processing timelines and enhancing the development of intuition regarding the effects of processing parameters on results.
We survey possibility of mutualistic interactions between RNA and a plausible prebiotic protein ancestor, depsipeptides, is explored. We see that RNA and cationic depsipeptides can form direct interactions. We also see that these interactions result in increased thermal stability of folded RNA structure and increased lifetimes for depsipeptides. The findings imply that the interdependencies of RNA and protein extends to the earliest stages in the development of life.
We observe the interchangeability of divalent metals within the translation system. Divalent metals, principally Mg2+, is a critical cofactor in many translation components. Other similar metals like Fe2+ and Mn2+ were once more abundant and may have played similar biological roles. We find that Fe2+¬ and Mn2+ can maintain translation structures and mediate translation itself in a manner comparable to Mg2+, implicating all three metals as cofactors in early stages of ribosomal evolution.
We resurrect ancestral states of the ribosome that represent the earliest catalytic core, the PTC. Motifs of ribosomal evolution are used to design and recapitulate the rRNA fragments that make up the PTC. Structural characterization of these fragments provides evidence for an evolutionary trajectory characterized by stepwise growths in ribosomal structures with concomitant conservation of preexisting structure.