Template Directed Ligation of RNA Oligomers

Abstract

The key to the RNA world hypothesis is the ribozyme, an information and catalytic agent that preceded proteins and DNA. Prior to ribozymes the sequences of RNA needed to build up to a length that could potentially be a ribozyme. This research focuses on computational modelling of hydrolysis, polymerization, and template-directed ligation to determine sequence patterns and characteristics that may have emerged due to these simple processes. A model containing L- and D-chirality monomers is used that incorporates the advantage of being a uniform chirality to achieve chiral symmetry breaking. Another chirality model is used where being uniform provides no advantage and a symmetry breaking still occurs. Beyond chirality we look at nucleobase models where we use a two letter alphabet containing adenine and uracil to determine symmetry breaking in sequence space. This results in self-complementary sequences dominating this model at all ligation rates but under certain initial conditions including high concentration, other types of sequences can be dominant. If a third base, guanine is added to this model a wobble base is created. In these models the self-complementary sequences containing uracil are the most prevalent due to uracil’s ability to pair with both adenine and guanine. Finally, upon adding a fourth base to the model guanine also becomes a wobble pair and the sequences containing uracil and guanine dominate the system for low ligation rates but at higher rates the uniform uracil and guanine sequences dominate. For each model a version is run with the templating reaction scaling linearly with the number of binding sites and without, where all templates are equally good. Generally, the scaling causes symmetry breakings at lower ligation values for each model.