Fig. 1. Experimental and computational pipeline for a guided exploration of the F1*U ribozyme fitness landscape.

a Fitness landscape of a ribozyme is sparsely populated where peaks of activities are separated by extensive valleys of deleterious genotypes. Therefore, evolutionary escape from a local optimum towards a distant peak can be challenging. b Outline of ribozyme library assay and evolution process using deep sequencing with in silico selection, recombination, and mutation. Sequences in generation 8 were evolved using a deep-learning classification model.