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MBE Advance Access originally published online on September 4, 2008
Molecular Biology and Evolution 2008 25(11):2483-2492; doi:10.1093/molbev/msn195
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© The Author 2008. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Research Articles

Analyzing the Evolution of RNA Secondary Structures in Vertebrate Introns Using Kimura's Model of Compensatory Fitness Interactions

Robert Piskol and Wolfgang Stephan

Department of Biology II, Section of Evolutionary Biology, Ludwig-Maximilians-University, Munich, Germany

E-mail: piskol{at}bio.lmu.de.

Accepted for publication August 26, 2008.

Previous studies have shown that splicing efficiency, and thus maturation of pre-mRNA, depends on the correct folding of the RNA molecule into a secondary or higher order structure. When disrupted by a mutation, aberrant folding may result in a lower splicing efficiency. However, the structure can be restored by a second, compensatory mutation. Here, we present a logistic regression approach to analyze the evolutionary dynamics of RNA secondary structures. We apply our approach to a set of computationally predicted RNA secondary structures in vertebrate introns. Our results are consistent with the hypothesis of a negative influence of the physical distance between pairing nucleotides on the occurrence of covariations, as predicted by Kimura's model of compensatory evolution. We also confirm the hypothesis that longer local secondary structure elements (helices) can accommodate a larger number of covariations, wobbles, and mismatches. Furthermore, we find that wobbles and mismatches are more frequent in the middle of a helix, whereas covariations occur preferentially at the helix ends. The GC content is a major determinant of this pattern.

Key Words: RNA secondary structure • covariation • compensatory mutation • introns

Hideki Innan, Associate Editor


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