Bioinformatic analysis of the neutrality of RNA secondary structure elements across genotypes reveals evidence for direct evolution of genetic robustness in HCV.

The properties and origin of genetic robustness have recently been investigated in several works that examined microRNA stem-loop structures, and a variety of conclusions have been reached without agreement. Considering that this is a universal phenomenon that is not restricted to miRNAs, we recall the original work on this topic that began from looking at viral RNAs of several types. We provide a link to this work by examining the neutrality of HCV structural elements, performing a detailed bioinformatic analysis using RNA secondary structure predictions across genotypes. This study provides supporting evidence for direct evolution of genetic robustness that is not limited to noncoding RNAs participating in gene regulation, but includes functionally important structural elements of the hepatitis C virus (HCV) that show excess of robustness beyond the intrinsic robustness of their stem-loop structure. These findings further support the adaptive behavior of genetic robustness in functional RNAs of various types that seem to have evolved with selection pressure towards increased robustness.