Fitness Landscapes of Ribozymes

Evolutionary outcomes are difficult, if not impossible, to predict, largely because the effect of any possible mutation is unknown. In other words, understanding evolution requires detailed knowledge of the relationship between sequence and activity, or the fitness landscape. Molecules explore the fitness landscape in sequence space during evolution, much as proteins explore the folding landscape in conformational space. Inspired by the RNA World theory of early life, in which RNA would carry information and also perform catalytic functions, we study the emergence and evolution of functional RNAs. Our experimental efforts focus on mapping complete fitness landscapes of ribozyme activity. We also study how confinement in a vesicle affects RNA activity and structure. These studies inform our understanding of the likelihood of emergence of function and the roles of chance vs. natural selection in prebiotic evolution.