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Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency
Published on: June 16, 2011
Occurrence, function and evolutionary origins of '2A-like' sequences in virus genomes
Garry A Luke1, Pablo de Felipe1, Alexander Lukashev2
1Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
The Journal of General Virology
|March 18, 2008
Summary
Viral 2A sequences mediate polyprotein cleavage through ribosome skipping. These sequences have evolved multiple times independently across diverse virus families, indicating homoplasy.
Area of Science:
- Molecular Biology
- Virology
- Evolutionary Biology
Background:
- The 2A sequence is an oligopeptide known to induce ribosome skipping, resulting in the apparent cleavage of viral polyproteins.
- Initially identified in picornaviruses, 2A-like sequences are also present in various mammalian and insect viruses.
Purpose of the Study:
- To identify and characterize novel 2A-like sequences across different viral taxa.
- To investigate the functional activity of these newly identified sequences in mediating polyprotein cleavage.
- To explore the evolutionary origins and distribution of 2A-like sequences in viruses.
Main Methods:
- Database analysis using a conserved motif specific to 2A/2A-like sequences.
- Functional assessment of newly identified 2A-like sequences (30 amino acids) by insertion into a reporter polyprotein system.
- Phylogenetic analysis of 2A-like sequences and RNA-dependent RNA polymerases (RdRps).
Main Results:
- The study identified numerous novel 2A-like sequences.
- These sequences were categorized based on their cleavage efficiency: the majority exhibited high cleavage activity, while a subset showed lower efficiency, producing uncleaved polyprotein forms.
- Phylogenetic analyses suggested multiple independent acquisitions of 2A-like sequences throughout viral evolution.
Conclusions:
- 2A-like sequences have been acquired independently multiple times during virus evolution.
- While 2A sequences within a viral family are likely homologous, their presence across different families suggests homoplasy (convergent evolution).
- The functional diversity in cleavage efficiency highlights the varied roles and evolutionary trajectories of these sequences.
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