Fig. 6: Evolutionary pathways for increasing activity on different substrates.

Each circular ‘pie’ represents a single sequence, whose catalytic enhancement for each substrate is shown by sector shading according to the heat map legend. For each family, the wild-type and the ribozymes having the six highest catalytic enhancements for each substrate are included. The wild-type sequence in each family is highlighted by a blue circle; the most active sequence for each substrate is indicated by a green sector outline for the substrate. Among the set of high-activity sequences, every pair of sequences for which Hamming distance d = 2 was examined to identify intervening sequences (d = 1 to both sequences of the pair) having substantial overall activity (\({\sum }_{X}{r}_{s}^{{BXO}} > 30\)). The intervening sequences are also shown in the plot. Lines connect sequences where d = 1. Sequences and catalytic enhancement values are given in Supplementary Table 3. Source data are provided as a Source Data file.