Figure 1

Relationship of the observed-to-expected numbers of mutations in different evolutionary rate categories. (A) Disease-associated mutations, DAMs (red). (B) Non-synonymous SNPs (blue), nSNPs. (C) Synonymous SNPs, sSNPs (black). The mid-values of the position rate categories are given in the X-axis (see also Table 1). The expected number of mutations at the amino acid positions belonging to a given rate index category, i, was computed as E_i = (n_i/N) × M, where n_i is the number of amino acid positions belonging to the i th category, N is the total number of amino acid positions, and M is the total number of disease mutations (or SNPs) used in the analysis. The significance of the deviations of the observed values from the expected was evaluated by a χ² test. The significance of the deviations from the random expectations for DAMs was P << 0.01 (χ² = 1318, df = 7), for non-synonymous SNPs was P << 0.01 (χ² = 1586, df = 7); and for synonymous SNPs was P > 0.05 (χ² = 7.2, df = 7). The observed correlations are significant at a 1% level for DAMs (R² = 0.95) and nSNPs (R² = 0.92), and the correlation is insignificant for synonymous SNPs (R² = 0.21).