Protein sequence alignments substitution tables

PAM Point Accepted Mutation. The PAM matrix is a frequency table representing substitution rates for closely related proteins at the particular evolutionary distance represented by multiple sequence alignments. 

Kelch and WD repeats consist of repeated sequence motifs with hallmark residues spaced at regular intervals (Fig. 1). In each case, only a handful of residues arc consistently conserved (bold residues in Fig. 1 sequence alignments) and even these positions can tolerate substitutions, making the identification of all repeats by sequence scanning algorithms alone difficult. In a number of cases, additional repeats present in a protein were only recognized after structural determination (Table 1). 

The relationships between nucleotide substitution rates in eoding sequences and predicted (on the basis of a consensus of flve methods) secondary structures of encoded proteins were investigated by Chiusano et al. (1999) on 34 alignments, each one of which comprised sequences belonging to at least four mammalian orders. The rates of synonymous and nonsynonymous substitutions were found not to be signifleantly diflerent in aperiodic and o-helix, whereas they were significantly lower in /3-strand, the most hydrophobic structure, compared to the other two structures (see Table 10.1). Expeetedly, in all cases nonsynonymous rates were lower than synonymous rates. 

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