Sequence conservation corresponds to intolerant positions. (Top) Sequence logo representation (Schneider and Stephens 1990) of the LacI multiple alignment for positions 5–38, a region involved in binding DNA. At each position, the stack of letters indicates which amino acids appear in the alignment, and the total height of the stack is a measure of conservation. (Bottom) Number of substitutions deleterious to LacI function at the corresponding positions (Markiewicz et al. 1994; Suckow et al. 1996). Positions with high conservation, such as 19–23, do not tolerate substitutions. Positions with low conservation, such as 26–28, can tolerate most substitutions. Positions 17 and 18 appear diverse in the alignment but cannot tolerate most substitutions. The side chains of these residues are involved in DNA-specific recognition (Chuprina et al. 1993) that is not conserved among the paralogous sequences.
