Identification of significant conservative and variable regions in homologous protein sequences.

A set of aligned homologous protein sequences is divided into 2 groups consisting of m and n sequences. Each group contains sequences from the most related species. Value of the position variability of homologous proteins sequences is defined as a number of failures to coincide in comparison of all possible m.n pairs of amino acid residues (each from a different group) in that position divided by m.n. The variability value plotted vs the sequence position number with a window of 10 positions gives the intergroup variability profile (VP). Area of the figure included between the VP and its mean value line characterizes the overall irregularity of amino acid substitutions along the protein sequences. If the area value S is greater than the average area Sr for 1000 random VPs by more than 2 standard deviation units (sigma), the real VP extrema containing the surplus of area S-(Sr + 2 sigma) are cut off. The cut-off stretches are likely to be significant variable and conservative regions. Intergroup comparisons of protein sequences reveal high overall irregularity of amino acid substitutions and identify variable and conservative regions for all considered families of proteins: phospholipases A2, aspartate aminotransferases, alpha-subunits of Na+,K(+)-ATPase, L- and M-subunits of photosynthetic bacteria photoreaction centre, and human rhodopsins.