Information-theoretic indices and an approximate significance test for testing the molecular clock hypothesis with genetic distances

Abstract

Distance-based phylogenetic methods are widely used in biomedical research. However, distance-based dating of speciation events and the test of the molecular clock hypothesis are relatively underdeveloped. Here I develop an approximate test of the molecular clock hypothesis for distance-based trees, as well as information-theoretic indices that have been used frequently in model selection, for use with distance matrices. The results are in good agreement with the conventional sequence-based likelihood ratio test. Among the information-theoretic indices, AICu is the most consistent with the sequence-based likelihood ratio test. The confidence in model selection by the indices can be evaluated by bootstrapping. I illustrate the usage of the indices and the approximate significance test with both empirical and simulated sequences. The tests show that distance matrices from protein gel electrophoresis and from genome rearrangement events do not violate the molecular clock hypothesis, and that the evolution of the third codon position conforms to the molecular clock hypothesis better than the second codon position in vertebrate mitochondrial genes. I outlined evolutionary distances that are appropriate for phylogenetic reconstruction and dating.