RNA sequence evolution with secondary structure constraints: Comparison ofsubstitution rate models using maximum-likelihood methods

We test models for the evolution of helical regions of RNA sequences, where the base pairing constraint leads to correlated compensatory substitutions occurring on either side of the pair. These models are of three types: 6-s tate models include only the four Watson-Crick pairs plus GU and UG; 7-stat e models include a single mismatch state that combines all of the 10 possib le mismatches; 16-state models treat all mismatch states separately. We ana lyzed a set of eubacterial ribosomal RNA sequences with a well-established phylogenetic tree structure. For each model, the maximum-likelihood values of the parameters were obtained. The models were compared using the Akaike information criterion, the likelihood-ratio test, and Cox's test. With a hi gh significance level, models that permit a nonzero rate of double substitu tions performed better than those that assume zero double substitution rate . Some models assume symmetry assumption performed slightly better, but the tests did not all agree on the significance level. The most general time-r eversible model significantly outperformed any of the simplifications. We c onsider the relative merits of all these models for molecular phylogenetics .