SIFT matrix validation. A. The number of SIFT intolerant mutations in each conserved positions (X axis) are plotted vs. their corresponding pair-wise mismatches count of the positional conservation score calculation. Except the large differences in five positions (49, 123, 149, 185 and 262 marked in circles) there is a high agreement between the two methods (r = 0.73 P < 10-5). (B) The number of SIFT intolerant mutations (X axis) in each of 245 human OR pseudogenes are plotted against the number of coding frame disruptions in their sequences (filled squares) Overall, a high positive correlation is observed even when only frame disruptions between TM1-TM7 are considered (empty circles) (r = 0.75 P < 10-5, r = 0.73 P < 10-5 respectively). Thus, the data in these plots suggests that the SIFT matrix is a good indicator for deviation from selective constraints.