Evolutionary lock-in and the origin of modularity in RNA structure

Modularity is a hallmark of biological organization and a important source of evo-lutionary novelty1–3. Yet, the origin of modules remains a problem for evolutionary biology, even in the case of the most basic protein or RNA domains4. Biological mod-ularity has been defined on many levels including genetic, morphological and develop-mental. The task of creating a general theory for the origins, ubiquity and function of modularity requires the synthesis of these perspectives. The first step in understanding the causes and consequences of modularity is to define it. The second step is to formulate methods of detecting it. The third is to build models and design experiments to study its origins and evolutionary implications. In this chapter we offer a rigorous definition of modularity in RNA. It is the parti-tioning of molecules into subunits that are simultaneously independent with respect to their thermodynamic environment, genetic context, and folding kinetics. On the varia-tional level, the module consists of a stretch (or stretches) of contiguous ribonucleotides held together by a covalent backbone. On the functional level, the relevant interactions include the covalent bonds of adjacent ribonucleotides and hydrogen bonds betwee