Occurrence, function and evolutionary origins of '2A-like' sequences in virus genomes

J Gen Virol. 2008 Apr;89(Pt 4):1036-1042. doi: 10.1099/vir.0.83428-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biological Evolution
  • Cysteine Endopeptidases / genetics*
  • Cysteine Endopeptidases / metabolism*
  • Evolution, Molecular
  • Genome, Viral*
  • Humans
  • Molecular Sequence Data
  • Picornaviridae / genetics*
  • Picornaviridae / metabolism
  • Picornaviridae Infections / virology*
  • Polyproteins / genetics
  • Polyproteins / metabolism*
  • Protein Biosynthesis
  • Ribosomes / metabolism
  • Sequence Alignment
  • Viral Proteins / genetics*
  • Viral Proteins / metabolism*


  • Polyproteins
  • Viral Proteins
  • Cysteine Endopeptidases