Sequence divergence among orthologous proteins was characterized with 34 amino acid replacement matrices, sequence context analysis, and a phylogenetic tree. The model was trained on very large datasets of aligned protein sequences drawn from 15 organisms including protists, plants, Dictyostelium, fungi, and animals. Comparative tests with models currently used in phylogeny, i.e., with JTT+Γ±F and WAG+Γ±F, made on a test dataset of 380 multiple alignments containing protein sequences from all five of the major taxonomic groups mentioned, indicate that our model should be preferred over the JTT+Γ±F and WAG+Γ±F models on datasets similar to the test dataset. The strong performance of our model of orthologous protein sequence divergence can be attributed to its ability to better approximate amino acid equilibrium frequencies to compositions found in alignment columns. [ABSTRACT FROM AUTHOR]