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

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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.

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Acknowledgments

The authors would like to thank the reviewers and the editors of the paper for their constructive comments, which contributed to an improved presentation. The authors would also like to thank the Super Biomed Computation Center at Beijing Institute of Health Administration and Medicine Information for providing computing resources. This work was supported by grants from the National High Technology Research and Development Program of China (No. 2007AA02Z311 and No. 2006AA02Z304) and Grants from the National Nature Science Foundation of China (No. 30700139 and No. 30600120).

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Correspondence to Xiaochen Bo or Shengqi Wang.

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The authors wish it to be known that, in their opinion, the authors Wenjie Shu and Ming Ni should be regarded as joint first authors.

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Shu, W., Ni, M., Bo, X. et al. In Silico Genetic Robustness Analysis of Secondary Structural Elements in the miRNA Gene. J Mol Evol 67, 560–569 (2008). https://doi.org/10.1007/s00239-008-9174-5

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  • DOI: https://doi.org/10.1007/s00239-008-9174-5

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