021 024 035 036 046 048 054 055 056 063 129 140 145 162 171 172 182 191 192 200 203 204 212 215 216 Gene Family Name EGF_Growth factor IL_18_BP (Bsh_D7L) Kelch_like_ (Cop_C2L) Unknown (Cop_C1L) Unknown (Cop_K7R) Apoptosis inhibitor (mitochondrial associated) Unknown (Cop_F6L) Unknown (Cop_F7L) Cytoplasmic protein (Cop_F8L) Unknown (Cop_F14L) Carbonic anhydrase Virion Core_protein (Cop_A4L) Membrane protein (Cop_A9L) RNA pol 132 (RPO132) Unknown (YMTV_120.5L) Unknown (Cop_A31R) Semaphorin Unknown (Cop_A47L) Thymidylate kinase Hemagglutinin Schlafen (Cop_B2R) Ankyrin (Cop_B4R) Ser_Thr_Kinase (Cop_B12R) IL_1_beta receptor Unknown (Cop_B17L) Category Host Response Modifier Host Response Modifier Host Response Modifier Unknown Entry/Exit Host Response Modifier Unknown Unknown Unknown Unknown Entry/Exit RNA metabolism Unknown Host Response Modifier Host Response Modifier Unknown DNA metabolism Host Response Modifier Host Response Modifier Unknown Unknown Host Response Modifier Unknown C2L C1L K7R F1L F6L F7L F8L F14L D8L A24R A30.5L A31R A39R A47L A48R A56R B2R B4R B12R B15R B17R VACV-Cop ORF C11R Specific Function EGF homolog with mitogenic activity Inhibition of IL-18 activity Structure/Assembly A4L Structure/Assembly A9L inhibitor of pattern recognition receptor signalling pathway localizes to mitochondria and inhibits apoptosis Cytoplasmic localization, unknown function Binds Chondroitin Sulfate on cell surface associated with virion core and membranes located on virion membrane, essential for morphogenesis Component of RNA polymerase Esteban and Hutchinson BMC Genomics 2011, 12:261 http://www.biomedcentral.com/1471-2164/12/261 Table 1 Genes under diversifying selection identified by both models ORF Number in DNA or RNA metabolism, as well as the majority of proteins used to assemble or form the structure of the virion (87%) are found in the virion. Focusing on the 25 genes identified by both models, host-response modifiers and genes of unknown function make up the largest proportions, 36% and 40%, respectively (Figure 3A). Of the 6 remaining genes, 5 are found in the virion (Thy- midine kinase is not found in the virion). Identification of specific residues under diversifying selection For each gene identified as experiencing diversifying selection, the posterior probabilities of each site falling into the three categories were calculated using a Bayes empirical Bayes (BEB) analysis [18]. For each gene, every codon was assigned to either the purifying, neutral or diversifying site classes. Two examples are shown: the Interleukin-18 binding protein (IL-18BP) (Figure 4A) and the mitochondrial associated apoptosis inhibitor (Figure 4B). As with most genes, most codons of the IL- 18BP gene are under purifying selection, with a small proportion under neutral or diversifying selection. For example, the posterior probabilities for site W124 are 0.000, 0.057, and 0.942 for purifying, neutral and diversi- fying selection, thus the site is highly likely to be under diversifying selection. A total of 8 specific sites are Unknown Unknown Unknown Unknown Unknown Unknown Unknown Induces IL-6 and IL-8 secretion from monocytes Unknown Thymidylate kinase activity prevents cell-cell fusion, present on EEV and cell surface Virulence factor in CMLV Unknown Unknown Unknown Inhibits IL-1 beta activity Page 4 of 12 Virion No No No No No No No No No No Yes Yes Yes Yes No Yes No No No Yes No No No No No