Virus sequences were obtained from GenBank in May 2009, updated in October 2010, and processed using BLAST, EMBOSS and ClustalW (52) (53) (54) . The accession numbers of all sequences used are given in the Supplementary Data. Coding sequences were extracted, translated, aligned with ClustalW and back-translated to nucleotide sequence alignments, and manually adjusted in a few cases. For the synonymous site conservation plots, alignment columns in which the reference sequence ( Figure 4 ) contained gap characters were removed so that the plots are in reference sequence coordinates. RNA structures were predicted using a combination of Vienna RNA RNAfold and alidot, pknotsRG and manual inspection (55, 56) .