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RNA sequence evolution with secondary structure constraints: comparison of substitution rate models using

N J Savill1, D C Hoyle, P G Higgs

  • 1School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.

Genetics
|January 5, 2001
PubMed
Summary

We evaluated RNA sequence evolution models, finding that allowing double substitutions and using a general time-reversible model significantly improves phylogenetic analysis accuracy. These RNA models are crucial for understanding evolutionary relationships.

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Area of Science:

  • Evolutionary biology
  • Molecular biology
  • Bioinformatics

Background:

  • RNA helical regions evolve with base pairing constraints, leading to compensatory substitutions.
  • Existing models vary in complexity, from simple pairings to detailed mismatch states.

Purpose of the Study:

  • To compare the performance of different evolutionary models for RNA helical regions.
  • To determine the best model for analyzing eubacterial ribosomal RNA sequences in phylogenetics.

Main Methods:

  • Analysis of eubacterial ribosomal RNA sequences using established phylogenetic trees.
  • Testing of 6-state, 7-state, and 16-state models with varying assumptions (e.g., double substitutions, symmetry).
  • Model comparison using Akaike information criterion, likelihood-ratio test, and Cox's test.

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Main Results:

  • Models permitting a nonzero rate of double substitutions significantly outperformed those assuming zero rate.
  • Relaxing symmetry assumptions between base pairs slightly improved model performance.
  • The most general time-reversible model demonstrated superior performance over simplified models.

Conclusions:

  • The choice of evolutionary model significantly impacts phylogenetic accuracy for RNA sequences.
  • General time-reversible models that account for double substitutions offer the most robust framework for RNA phylogenetics.