Evolutionary analyses of DNA sequences subject to constraints of secondary structure

Evolutionary models appropriate for analyzing nucleotide sequences that are subject to constraints on secondary structure are developed. The models consider the evolution of pairs of nucleotides, and they incorporate the effects of base-pairing constraints on nucleotide substitution rates by introducing a new parameter to extensions of standard models of sequence evolution. To illustrate some potential uses of the models, a likelihood-ratio test is constructed for the null hypothesis that two (prespecified) regions of DNA evolve independently of each other. The sampling properties of the test are explored via simulation. The test is then incorporated into a heuristic method for identifying the location of unknown stems. The test and related procedures are applied to data from ribonuclease P RNA sequences of bacteria.