Coevolution In RNA Molecules Driven By Elective Constraints

Understanding intra-molecular coevolution can help elucidate various structural andfunctional constraints acting on molecules and can be useful in predicting molecular structureand interactions. In this study, we used5S rRNA as a template to investigate how selectiveconstraints have shaped RNA evolution. The nonrandom occurrence of paired differencesalong the phylogenetic trees, the high rate of compensatory evolution, and the high TIR scores(the ratio of the numbers of terminal to intermediate states) we observed indicate thatsignificant positive selection has driven the evolution of coevolutionary interactions. Wefound three mechanisms of compensatory evolution: the main mechanism was theWatson-Crick interaction, followed by complex interactions between multiple sites andinteractions of stems and loops. Coevolutionary interactions between sites were observed tobe highly dependent on the structural and functional environment in which they occurred.Coevolution appeared to occur mostly between sites that are close to loops or bulges withinstructurally or functionally important helices, which may be under weaker selectiveconstraints than other stem positions. Breaking these pairs would directly increase the size ofthe adjoining loop or bulge, causing a partial or total structural rearrangement. Taken together,our results indicate that sequence coevolution was a direct result of maintaining optimalstructural and functional integrity.