Neutral Networks of Interacting RNA Secondary Structures

RNA molecules interact by forming inter-molecular base pairs that compete with the intra-molecular base pairs of their secondary structures. We investigate the patterns of neutral mutations in RNAs whose function is the interaction with other RNAs, i.e. the co-folding with one or more other RNA molecules. We find that (i) the degree of neutrality is much smaller in interacting RNAs compared to RNAs that just have to coform to a single externally prescribed target structure, and (ii) strengthening this contraint to the conservation of the co-folded structure with two or more partners essentially eliminates neutrality. It follows that RNAs whose function depends on the formation of a specific interaction complex with a target RNA molecule will evolve much more slowly than RNAs with a function depending only on their own structure.