Similarity analysis of sequences belonging to some protein families indicates the existence of highly variable positions. In this work, a method of interpretation of variability at these positions is presented. The proposed method extends out of the Dot-Matrix method with the possibility of making new analysis of similarity and consideration of physicochemical aspects of variability. These analyses have been made at two consideration levels, i.e. the amino-acid level and codon level. To make this possible, semihomologization and desemihomologization mechanisms have been introduced. As a result, the method of selection of sequences, which best represents the given protein family, has been proposed. A higher frequency of six-codon amino-acids at the highly variable positions has been identified, which can indicate that one-point mutation is the main mechanism of amino-acid codon evolution.