FIGURE 1 

Two possible relationships in mutation space between additive mutations (shown in green) and experimentally identifiable and beneficial sets of mutations (pink and yellow). In (A), most of the identifiable, beneficial mutations are nearly additive. In this case, the experimental techniques that focus only on the identification of additive mutations (pink) will reveal most of the identifiable beneficial mutations. In (B), only a small subset of all of the identifiable sets of mutations is identified. However, the results in Yoshikuni et al show that even if case (B) is the natural reality, the subspace of identifiable, beneficial, and additive mutations (pink) is of sufficient size to effect potent changes in enzymatic activity.