20] Mutation data matrix and its uses

Abstract

This chapter describes the mutation data matrix (MDM) and its application for comparing protein sequences. Basic to all sequence comparison is the concept of an alignment that defines the relationship between sequences on a residue-by-residue basis. Sequence comparison methods use a scoring matrix that assigns a value to each possible pair of aligned amino acids. One of the most widely used similarity measures is the mutation data matrix (MDM) developed by Dayhoff and colleagues. The first MDM, published in 1968, was derived from over 400 accepted point mutations between present-day sequences and inferred ancestral sequences. Within the Markovian model, the MDM is derived from a transition probability matrix in which each matrix element gives the probability that amino acid A will be replaced by amino acid B in one unit of evolutionary change. The diagonal elements give the probabilities that the amino acids will remain unchanged. The probability of an amino acid being replaced is estimated as its relative mutability, which is calculated as the ratio of the number of observed changes of an amino acid to its total exposure to change.