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Updated: Dec 25, 2025
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A Bioinformatics Pipeline for Investigating Molecular Evolution and Gene Expression using RNA-seq
Published on: May 28, 2021
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An Evolutionary Trace method defines functionally important bases and sites common to RNA families
Ilya B Novikov1, Angela D Wilkins2, Olivier Lichtarge2
1Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
Plos Computational Biology
|March 26, 2020
Summary
Phylogenetic analysis of functional non-coding RNAs (fncRNAs) reveals conserved nucleotide clusters crucial for molecular function. This evolutionary approach accurately predicts functional sites in RNA structures, similar to protein analysis.
Area of Science:
- Molecular Biology
- Bioinformatics
- Evolutionary Biology
Background:
- Functional non-coding RNAs (fncRNAs) are vital regulators of gene expression, genome stability, and cellular processes.
- Understanding the structure-function relationships of fncRNAs is crucial for deciphering their roles in health and disease.
- The evolutionary record offers insights into conserved functional elements within RNA sequences.
Purpose of the Study:
- To adapt the phylogenetic Evolutionary Trace (ET) paradigm, previously used for proteins, to identify functional determinants in RNA sequences.
- To map evolutionary important nucleotide clusters to specific functional regions within RNA structures.
- To assess the utility of ET analysis for predicting functional sites in RNA.
Main Methods:
- Applied the phylogenetic Evolutionary Trace (ET) paradigm to a dataset of 1070 functional RNAs, including ribosomal RNA.
- Assigned evolutionary importance ranks to individual bases based on sequence comparisons and phylogenetic analysis.
- Correlated the quantitative quality of evolutionary important nucleotide clusters with known functional regions.
Main Results:
- Identified clusters of top-ranked evolutionary important bases within the secondary and tertiary structures of functional RNAs.
- These clusters corresponded to functionally critical regions involved in catalysis, protein/drug binding, and post-transcriptional modification.
- The correlation between cluster quality and functional region identification improved the prediction of functional sites.
- Reported novel, potentially functional ET nucleotide clusters in the ribosome.
Conclusions:
- Phylogenetic analysis, using the ET paradigm, is a powerful tool for identifying functional determinants and sites in RNA sequences and structures.
- Evolutionary constraints on sequence, structure, and function are conserved between structured RNAs and proteins.
- RNA ET analysis provides valuable insights into the molecular mechanisms of RNA function and is applicable to various RNA types, including ribosomal RNA.
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