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Table 1 A hypothetical example MSA that illustrates the problem of uneven site conservation.

From: Identification of specificity determining residues in peptide recognition domains using an information theoretic approach applied to large-scale binding maps

Sequence/Site 1 2 3 4
I A V A C
II A V C D
III T Y D E
IV T Y E C
  1. Sites 1 and 2 are truly covarying, while sites 3 and 4 are random and unrelated. However, as sites 3 and 4 have higher entropy values than sites 1 and 2, the resulting mutual information between sites 3 and 4 is also higher than that between sites 1 and 2 (see main text for the calculations).