SHAPE MATTERS: EFFECT OF POINT MUTATIONS ON RNA SECONDARY STRUCTURE

Abstract

A suitable model to dive into the properties of genotype-phenotype landscapes is the relationship between RNA sequences and their corresponding minimum free energy secondary structures. Relevant issues related to molecular evolvability and robustness to mutations have been studied in this framework. Here, we analyze the one-mutant neighborhood of the predicted secondary structure of 46 different RNAs, including tRNAs, viroids, larger molecules such as Hepatitis-δ virus, and several random sequences. The probability distribution of the effect of point mutations in linear structural motifs of the secondary structure is well fit by Pareto or Lognormal probability distributions functions, independent of the origin of the RNA molecule. This extends previous results to the case of natural sequences of diverse origins. We introduce a new indicator of robustness, the average weighted length of linear motifs (AwL) and demonstrate that it correlates with the average effect of point mutations in RNA secondary structures. Structures with a high AwL value display the highest structural robustness and cluster in particular regions of sequence space.