Key result
Newly identified 2A-like sequences in virus genomes mediate varying levels of cleavage activity and appear to have been acquired independently multiple times during virus evolution.
2A-like sequences, which mediate ribosome skipping, appear to have evolved independently multiple times across different virus families.
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Does not yet alter clinical viral management; leaves open evolutionary and functional validation across virus families.
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.
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Luke et al. (2008) studied Viral genomes. 2A-like sequences was evaluated on Cleavage activity. Newly identified 2A-like sequences in virus genomes mediate varying levels of cleavage activity and appear to have been acquired independently multiple times during virus evolution.
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