Using small samples to estimate neutral component size and robustness in the genotype–phenotype map of RNA secondary structure

Abstract

In genotype–phenotype (GP) maps, the genotypes that map to the same phenotype are usually not randomly distributed across the space of genotypes, but instead are predominantly connected through one-point mutations, forming network components that are commonly referred to as neutral components (NCs). Because of their impact on evolutionary processes, the characteristics of these NCs, like their size or robustness, have been studied extensively. Here, we introduce a framework that allows the estimation of NC size and robustness in the GP map of RNA secondary structure. The advantage of this framework is that it only requires small samples of genotypes and their local environment, which also allows experimental realizations. We verify our framework by applying it to the exhaustively analysable GP map of RNA sequence length L = 15, and benchmark it against an existing method by applying it to longer, naturally occurring functional non-coding RNA sequences. Although it is specific to the RNA secondary structure GP map in the first place, our framework can probably be transferred and adapted to other sequence-to-structure GP maps.