Related Experiment Video
Updated: Jul 4, 2026
10:34
Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
Published on: December 9, 2022
Compensatory evolution in RNA secondary structures increases substitution rate variation among sites
Jennifer L Knies1, Kristen K Dang, Todd J Vision
1Department of Biology, University of North Carolina, Chapel Hill, USA. Jennifer_Knies@brown.edu
Molecular Biology and Evolution
|June 7, 2008
Summary
Molecular interactions limit evolution. Our study shows the ratio of transition to transversion substitutions (kappa) is higher at interacting RNA sites, supporting evolutionary models. This finding may aid in evaluating RNA secondary structures.
Area of Science:
- Molecular Biology
- Evolutionary Biology
- Bioinformatics
Background:
- Biological molecule interactions (RNA-RNA, protein-protein, RNA-protein) influence molecular evolution rates and trajectories.
- Kimura's model of compensatory evolution provides a framework for understanding evolution at interacting sites.
Purpose of the Study:
- To extend Kimura's model to predict the ratio of transition to transversion substitutions (kappa) at interacting sites.
- To test the model's prediction that kappa is higher at interacting sites compared to independent sites using RNA secondary structures.
Main Methods:
- Phylogenetic analysis of 10 RNA secondary structures.
- Comparison of kappa estimates in paired (stems) and unpaired (loops) sites.
- Statistical analysis to evaluate model predictions against empirical data.
Main Results:
- Eight out of 10 RNA structures matched quantitative predictions, with kappa higher in paired sites (kappa(p) > kappa(u)).
- Nine out of 10 structures supported the qualitative prediction kappa(p) > kappa(u).
- The HIV Rev response element showed an exceptional pattern (kappa(p) < kappa(u)), potentially explained by APOBEC3 enzymes.
Conclusions:
- The ratio of transition to transversion substitutions (kappa) is a useful indicator of molecular interactions and evolutionary constraints.
- The findings support the role of molecular interactions in shaping evolutionary trajectories.
- Kappa may serve as a diagnostic tool for validating proposed RNA secondary structures.
Related Concept Videos
02:05Gene Evolution - Fast or Slow?
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
02:05Gene Evolution - Fast or Slow?
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
00:43Bacterial RNA Polymerase
Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
01:53RNA Stability
Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
02:23RNA Editing
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...