In Silico Genetic Robustness Analysis of Secondary Structural Elements in the miRNA Gene

Abstract

Genetic robustness, insensitivity of the phenotype facing genetic mutations, is a fundamental and ubiquitously observed property of biological systems. In this study, we investigate the genetic robustness of the structural elements within native miRNA genes on a genome-wide scale. MicroRNAs (miRNAs) are a large family of endogenous noncoding RNAs that regulate gene expression at the posttranscriptional level. We examine the neutrality of the structural element in 1082 native pre-miRNAs from six species and demonstrate that the structural elements in native pre-miRNAs exhibit a significantly higher level of genetic robustness in comparison with structural elements within random pseudo pre-miRNAs. Hence, this excess robustness of structural elements in pre-miRNAs goes beyond the intrinsic robustness of the stem-loop structure. Furthermore, we show that it is not a by-product of a base composition bias. Interestingly, our data also demonstrate a difference in increased levels of average neutrality between structural elements. Remarkably, differential genetic robustness between structural elements is observed in both native and pseudo pre-miRNAs. Our results are much in agreement with previous experimental observations, and suggest that the genetic robustness of secondary structural elements in native pre-miRNAs, under different evolutionary selection pressures, may evolve due to its own selective advantage.