Average biochemical distances between the amino acid residues found in the normal and disease humans and in other species. (A) Relationship between the average Grantham distances estimated for the DAMs (red) and the time of onset of diseases (obtained from ). The numbers of genes are given in the parenthesis. Error bars show the standard error of the mean. (B) Correlation between the evolutionary rate and the average Grantham distance of the inter-specific amino acid substitutions (R2 = 0.88, P < 0.01) (green). The average Grantham distance was estimated by including all the changes (with respect to the human proteins) that occurred in the amino acid positions of the non-human proteins belonging to various rate indices. Only six rate index categories were included, as the two categories include only the invariable amino acid positions. Error bars show the standard error of the mean.