This research will study how gradual mutation accumulation can bring about sudden and dramatic changes to a simple genetic system. We are studying a ribonucleic acid (RNA) that can propagate genetically, but which also is able to act as an RNA enzyme, to chemically convert (cut or splice) other RNA fragments. The form that is most active in RNA cutting and the form that is most active in RNA splicing are genetically and chemically similar; they are separated by less than 20 mutations. We will study the biochemical properties of all the intermediary forms to see how activity of an RNA enzyme changes into its opposite. In some of the non-scientific critique of the evolutionary concepts, the very existence of such sudden changes in evolution have been cast into doubt, and we expect that the dissemination of the results of this research will help facilitate a discussion of how scientific experiments can address difficult questions in evolutionary biology. This research will bring together a graduate trainee in biomolecular sciences and a computational biologist, and these researchers will also participate in this univeristy's programs that are aimed at broadening the participation of groups underrepresented in science, mathematics, engineering and technology.
The activities of this research will reconstruct and evaluate the evolutionary pathways between two RNA molecules with two distinct structures and functions. RNA molecules are chosen because they allow analysis of both mutational changes and their functional consequences in high-throughput using modern sequencing technology. About one million intermediate forms between these two starting molecules will be constructed in the lab. Each of these intermediate sequences will be tested for their ability to perform each of the two functions. The results will be used to construct two ?fitness landscapes? that overlap. All possible pathways between peaks within and between the two landscapes will be explored computationally to predict how evolution could be aided or hindered by the structure of these landscapes, and to determine under what scenarios this type of evolutionary innovation is possible.
