On the PAM matrix model of protein evolution

The internal consistency of the PAM matrix model of protein evolution ishere investigated. The 1 PAM matrix has been constructed from amino acidreplacements observed in closely related sequences. Such replacements areof two types, those that do not require an intermediate amino acidreplacement and those that do. The second type of replacement mustgenerally be produced by a repetition of the first. This allows data on thefirst type to be used in predicting data on the second type so that someelements of the 1 PAM matrix may be used to predict others. A discrepancyof more than two orders of magnitude is found between the predictions andthe data when this is carried out. This is partly accounted for by an errorin constructing the matrix. However, it also seems necessary that the basicmodel be modified. Several possibilities are considered. One of these is toincorporate a site-dependent spectrum of mutabilities associated with eachamino acid.