From our consensus shuffling error rate data (Figure 3 ), we estimate the MutS selectivity factor M to be $2.2. Figure 5 shows some predictions that emerge from this model assuming typical length (2 kb), fragment sizes (200 bp) and error rates (1.8 errors/kb). Consensus shuffling is predicted to be most effective with smaller fragment sizes ( Figure 5A ). As mentioned above, smaller fragment sizes could be obtained by controlled digestion with DNase I (21) . In addition, multiple iterations of MutS filtering can have dramatic results on populations with few correct sequences ( Figure 5B ), although the model does not account for the differing specificity of MutS toward the various types of mismatches. The model also predicts that even modest improvements in the MutS selectivity factor through optimization of the MutS-DNA binding conditions and/or the use of a combination of MutS homologs with varying mismatch specificity (29) could dramatically improve the consensus shuffling protocol ( Figure 5C ). Coincidence filtering (N = S) is predicted to be effective for populations with low error rates per clone ( Figure 5D ) but becomes ineffective when the majority of re-hybridized duplexes contain mismatches.