Study of double and triple simultaneous substitutions of amino acids in cytochromes C.

A statistical analysis aimed at obtaining some informations on a possible correlation between simultaneous amino acid substitutions is proposed. This method is applied to a set of cytochrome C, at the level of tandem and triple substitutions separated along the peptide chain by 1 to 15 peptide bonds. Monte-Carlo simulations are performed and the results are compared. We find a significant occurrence of three adjacent amino acid substitutions in which the first replacement requires a two nucleotide substitution. A possible explanation of this fact is proposed on the basis of covarions.