A simple method to detect the heterogeneity of nucleotide substitution processes by measuring asymmetry in paired comparison.

A simple method is presented, which uses a chi2 statistic to measure asymmetry of the substitution matrix between two DNA sequences in order to test a homogeneity hypothesis of the substitution processes. In theory, this chi2 test holds irrespective of whether there is among-site (i) heterogeneity in substitution rates, (ii) correlation in evolutionary rates/models, and (iii) variation in substitution models. Computer simulations showed that the chi2 test is powerful under a variety of models of sequence evolution. Comparison of the eleven sequenced arthropod mtDNAs by using this test revealed that most of the observed evolutionary models were homogeneous between the two mosquitoes but not between Daphnia pulex or Artemia franciscan and the other arthropods, probably due to shifts to a high AT content. A comparison to Kumar and Gadagkar's test by computer simulation as well as empirical data analysis is also given.