title: Occurrence, function and evolutionary origins of '2A-like' sequences in virus genomes.
abstract: 2A is an oligopeptide sequence mediating a ribosome 'skipping' effect, producing an apparent 'cleavage' of polyproteins. First identified and characterized in picornaviruses, '2A-like' sequences are found in other mammalian viruses and a wide range of insect viruses. Databases were analysed using a motif conserved amongst 2A/2A-like sequences. The newly identified 2A-like sequences (30 aa) were inserted into a reporter polyprotein to determine their cleavage activity. Our analyses showed that these sequences fall into two categories. The majority mediated very high (complete) cleavage to separate proteins and a few sequences mediated cleavage with lower efficiency, generating appreciable levels of the uncleaved form. Phylogenetic analyses of 2A-like sequences and RNA-dependent RNA polymerases (RdRps) indicated multiple, independent, acquisitions of these sequences at different stages during virus evolution. Within a virus family, 2A sequences are (probably) homologous, but diverge due to other evolutionary pressures. Amongst different families, however, 2A/2A-like sequences appear to be homoplasic.
authors.affiliation: Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
authors.forename: Garry A
authors.initials: GA
authors.lastname: Luke
authors.affiliation: Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
authors.forename: Pablo
authors.initials: P
authors.lastname: de Felipe
authors.affiliation: Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow 142782, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lukashev
authors.affiliation: Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
authors.forename: Susanna E
authors.initials: SE
authors.lastname: Kallioinen
authors.affiliation: Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Bruno
authors.affiliation: Centre for Biomolecular Sciences, School of Biology, Biomolecular Sciences Building, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Ryan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D016679:Genome, Viral; D006801:Humans; D008969:Molecular Sequence Data; D010849:Picornaviridae / Q000235:genetics* / Q000378:metabolism; D010850:Picornaviridae Infections / Q000821:virology*; D020815:Polyproteins / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D012270:Ribosomes / Q000378:metabolism; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D020815:Polyproteins; D014764:Viral Proteins; D003546:Cysteine Endopeptidases