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Structure Unveils Relationships between RNA Virus Polymerases.

Heli A M Mönttinen1, Janne J Ravantti1, Minna M Poranen1

  • 1Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Viikki Biocenter 1, P.O. Box 56 (Viikinkaari 9), 00014 Helsinki, Finland.

Viruses
|March 6, 2021
PubMed
Summary

Protein structure analysis reveals the evolutionary history of RNA viruses. This structure-based phylogeny of RNA-dependent RNA polymerases (RdRps) offers a new classification system for RNA viruses.

Keywords:
RNA virusRNA virus taxonomyRNA-dependent RNA polymeraseprotein evolutionprotein structurestructural alignmentstructural conservationstructure comparison

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Area of Science:

  • Virology
  • Structural Biology
  • Evolutionary Biology
  • Bioinformatics

Background:

  • RNA viruses evolve rapidly, leading to quick loss of sequence similarity.
  • Traditional sequence-based phylogenetic methods are limited for studying RNA virus evolution.
  • Protein structures evolve slower than sequences, retaining detectable similarity for evolutionary inference.

Purpose of the Study:

  • To reconstruct the evolutionary history of RNA viruses using protein structure comparison.
  • To investigate the evolutionary relationships among viral RNA-dependent RNA polymerases (RdRps).
  • To develop a structure-based classification system for RNA viruses.

Main Methods:

  • Utilized an automated structural comparison method, homologous structure finder.
  • Performed comprehensive structural comparisons of diverse viral RdRps.
  • Constructed a structure-based phylogenetic tree using a common RdRp structural core.

Main Results:

  • Identified a conserved structural core of 231 residues in all characterized viral RdRps.
  • RdRp phylogenetic tree topology reflects functional differentiation and transcription mechanisms.
  • Structure-based classification aligns with existing RdRp-based RNA virus taxonomy but suggests alternative phylum organization.

Conclusions:

  • Protein structure comparison provides a robust method for RNA virus phylogeny, overcoming sequence limitations.
  • The identified RdRp structural core is a unifying feature across diverse RNA virus groups.
  • A structure-based phylogenetic framework offers insights into RNA virus evolution and classification, potentially revising higher taxonomic ranks.