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

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 b...

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Bibliographic Details
Published in:Molecular biology and evolution 2008-11, Vol.25 (11), p.2483-2492
Main Authors: Piskol, Robert, Stephan, Wolfgang
Format: Article
Language:English
Subjects:
Animals
Base Composition
Base Pair Mismatch
Base Pairing
Evolution, Molecular
Evolutionary biology
Humans
Introns
Models, Genetic
Molecular biology
Mutation
Nucleic Acid Conformation
Regression Analysis
Ribonucleic acid
RNA
RNA - chemistry
Vertebrates
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Summary: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.
ISSN:0737-4038
1537-1719
DOI:10.1093/molbev/msn195