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Fig. 8 | Genome Biology

Fig. 8

From: Non-base-contacting residues enable kaleidoscopic evolution of metazoan C2H2 zinc finger DNA binding

Fig. 8

Correlation of kaleidoscopic evolution with DNA-binding affinity of non-base-contacting residues. a Bar graphs showing evolutionary rates for C2H2-ZFs with varying DBF scores (left, non-base contacting; right, base-contacting). Extant C2H2-ZFs that have a single amino acid transition at the base-contacting residues and a different motif relative to their inferred ancestor (Pearson similarity < 0.1) are included. The normalized rate of kaleidoscopic evolution is defined as the ratio of mutation rate in base-contacting residues relative to the rest of the C2H2-ZF sequence. P values are based on Fisher’s transformation of Pearson correlation between rate of kaleidoscopic evolution and DBF score. b Change in DBF score of base-contacting residues of extant C2H2-ZFs relative to their ancestors, with bins corresponding to DNA-binding strength of non-base-contacting residues. P value calculations are the same as in (a). c Comparison of DBF scores for ancient vs. recent metazoan C2H2-ZFs. The first bin corresponds to C2H2-ZFs from high-confidence pedigrees with conserved base-contacting residues that originated in the last common ancestor of metazoans. The second bin corresponds to C2H2-ZFs from high-confidence pedigrees with base-contacting residues that date back to the ancestor of chordates or more recent. Error bars represent the standard error. The P value is based on Student’s t-test. d Average frequency of base-contacting residue combinations, plotted in bins of DBF score of base-contacting residue combinations themselves (x-axis), and maximum DBF score of their first-degree neighbors, i.e. other combinations that are only different at a single residue (y-axis). For example, a base-contacting residue combination with a DBF score of 0–0.2 that can be generated by a single mutation from another combination with a DBF score of 0.8–1 is found, on average, in 7.8 C2H2-ZFs. e The rate of kaleidoscopic evolution for C2H2-ZFs neighboring C2H2-ZFs of varying DBF score or (f) in varying C2H2-ZF array length. P values are based on Fisher’s transformation of Pearson correlations

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