in the 1970s. This matrix is calculated by observing the differences in closely related proteins. Because the use of very closely related homologs, the observed mutations are not expected to significantly change the common functions of the proteins. Thus the observed substitutions (by point mutations) are considered to be accepted by natural selection.

One PAM unit is defined as 1% of the amino acid positions that have been changed. To create a PAM1 substitution matrix, a group of very closely related sequences with mutation frequencies