The extent of change in activity is positively correlated with the number of nonsynonymous mutations the P450 has undergone relative to the neutral evolution parent. Each column shows the Pearson correlation between the number of nonsynonymous mutations and the absolute value of the logarithm of the fold change in activity for a different substrate, computed over all 34 P450 variants. The final column (ALL) is the correlation among the 6 × 34 pooled data points for all six substrates. The P-values are shown in parentheses; none of the correlations for the individual substrates are significant at a 1% level (due to the small number of data points), but the overall correlation for all substrates is highly significant. Substrate abbreviations are as defined in the legend to Figure 2.