Substitution matrix: Difference between revisions

Revision as of 01:53, 9 June 2021

Revision as of 04:46, 18 June 2021

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One of the first amino acid substitution matrices, the PAM ''([[Point accepted mutation|Point Accepted Mutation]])'' matrix was developed by [[Margaret Oakley Dayhoff|Margaret Dayhoff]] 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 corresponding to one PAM unit is chosen. Based on collected mutationaldatamutational data from this group of sequences, a substitution matrix can be derived. This PAM1 matrix estimates what rate of substitution would be expected if 1% of the amino acids had changed. The PAM1 matrix is used as the basis for calculating other matrices by assuming that repeated mutations would follow the same pattern as those in the PAM1 matrix, and multiple substitutions can occur at the same site. Using this logic, Dayhoff derived matrices as high as PAM250. Usually the [[PAM30|PAM 30]] and the PAM70 are used.

A matrix for more distantly related sequences can be calculated from a matrix for closely related sequences by taking the second matrix to a power. For instance, we can roughly approximate the WIKI2 matrix from the WIKI1 matrix by saying <math>W_2 = W_1^2</math> where <math>W_1</math> is WIKI1 and <math>W_2</math> is WIKI2. This is how the PAM250 matrix is calculated.