Superiority of a mechanistic codon substitution model even for protein sequences in Phylogenetic analysis

Sanzo Miyazawa

Nucleotide and amino acid substitution tendencies are characteristic of each species, organelle, and protein family. Hence, various empirical amino acid substitution rate matrices have needed to be estimated for phylogenetic analysis: JTT, WAG, and LG for nuclear proteins, mtREV for mitochondrial proteins, cpREV10 and cpREV64 for chloroplast-encoded proteins, and FLU for influenza proteins. On the other hand, in a mechanistic codon substitution model, in which each codon substitution rate is proportional to the product of a codon mutation rate and the ratio of fixation depending on the type of amino acid replacement, mutation rates and the strength of selective constraint on amino acids can be tailored to each protein family with additional 11 parameters. As a result, in the evolutionary analysis of codon sequences it outperforms codon substitution models equivalent to empirical amino acid substitution matrices. Is it superior even for amino acid sequences, among which synonymous substitutions cannot be identified?