PAM MATRICES

PAM stands for ‘Point Accepted Mutations’

PAM matrices are developed based on the PAM model of evolution. This model assumes that the evolutionary changes occur according to Markov Model which states that residue mutations are independent of previous mutations.

PAM is a unit of evolutionary divergence in which 1% of the amino acids had changed. This doesn’t mean that after 100 PAM’s all the aminoacids are different.

The PAM (Point Accepted Mutation) matrices were developed by Margaret Dayhoff in the 1970s. The basi for their approach is to obtain substitution data from alignments between very similar proteins, allowing for the evolutionary relationships of the protein families, and then extrapolate this information to longer evolutionary distances. They constructed hypothetical hylogenetic trees using Parsiminy method.

The similarity scores are obtained by taking the natural logarithms of the frequencies. Thus they have constructed the PAM1 Matrix. The 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 PAM 30 and the PAM70 are used.

A matrix for divergent 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 matrix2 from the matrix1 by saying 'Matrix2 Is Equal To The Square Of Matrix1'. This is how the PAM250 matrix is calculated.

Problems with PAM Matrices:

1) Evolutionary rates vary greatly with in a protein
2) Each position has its own 3-D environment
3) Environment changes over evolutionary time.