SynPAM—A Distance Measure Based on Synonymous Codon Substitutions

Measuring evolutionary distances between DNA or protein sequences forms the basis of many applications in computational biology and evolutionary studies. Of particular interest are distances based on synonymous substitutions since these substitutions are considered to be under very little selection pressure and therefore assumed to accumulate in an almost clock-like manner. SynPAM, the method presented here, allows the estimation of distances between coding DNA sequences based on synonymous codon substitutions. The problem of estimating an accurate distance from the observed substitution pattern is solved by maximum likelihood with empirical codon substitution matrices employed for the underlying Markov model. Comparisons with established measures of synonymous distance indicate that SynPAM has less variance and yields useful results over a longer time range.