MBE Advance Access published online on September 4, 2008
Molecular Biology and Evolution, doi:10.1093/molbev/msn195
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Research Article |
Analyzing the Evolution of RNA Secondary Structures in Vertebrate Introns Using Kimura's Model of Compensatory Fitness Interactions
1 Section of Evolutionary Biology, Ludwig-Maximilians-University, Munich, Germany
* Corresponding author, Robert Piskol, Section of Evolutionary Biology, LMU BioCenter, Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany, Phone: +49 89 2180 74 106, Fax: +49 89 2180 74 104, mail: piskol{at}bio.lmu.de
Received for publication July 1, 2008. Revision received August 18, 2008. Accepted for publication August 26, 2008.
Previous studies have shown that splicing efficiency, and thus maturation of premRNA, 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 (Kimura 1985). 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