An evaluation of the relatedness of proteins based on comparison of amino acid sequences

A procedure based on comparing amino acid residues was developed to examine the statistical consequences of practices commonly applied in sequence comparisons. A simple numerical method was devised to group amino acids into “homology sets” which allow consistent rather than ad hoc assignments of similar amino acids throughout polypeptide chains. By comparing sequences generated from random number tables it was possible to examine quantitatively the change in expectations contributed by the introduction of gaps into sequences. This method was also used to evaluate possibilities of gene duplication and recurring sequences resulting from convergent evolution for particular structural or functional requirements. Several specific proteins were investigated as illustrative examples. Rules of thumb were developed to indicate significant relatedness of two sequences beyond the expectations of chance.