Genetic robustness of let-7 miRNA sequence-structure pairs

Genetic robustness, the preservation of evolved phenotypes against genotypic mutations, is one of the central concepts in evolution. In recent years a large body of work has focused on the origins, mechanisms, and consequences of robustness in a wide range of biological systems. In particular, research on ncRNAs studied the ability of sequences to maintain folded structures against single-point mutations. In these studies, the structure is merely a reference. However, recent work revealed evidence that structure itself contributes to the genetic robustness of ncRNAs. We follow this line of thought and consider sequence-structure pairs as the unit of evolution and introduce the spectrum of inverse folding rates (IFR-spectrum) as a measurement of genetic robustness. Our analysis of the miRNA let-7 family captures key features of structure-modulated evolution and facilitates the study of robustness against multiple-point mutations.