Earlier findings support positive selection at sites involved in receptor and antigen binding [11, 62] . Five of the 18 codons in HA proposed by Bush et al., [63] to be under positive selection were found to have changed in our HA dataset of H3N2 since 1999, namely: pos 145, 156, 186, 193 and 226. In our H3 dataset (n = 204) site 199 was influenced by positive selection as calculated by FEL analysis, but no positively selected sites were found applying the more conservative SLAC method. Position 199 may be involved in receptor binding and influence on the virus ability to grow in eggs [10] . In a similar study on a slightly larger dataset (n = 284) positions 220 and 229 were found to be positively selected [11] . Another study found positions 13 and 236 [62] ; however, suggested positively selected sites may vary by the dataset applied, method used and the significance level selected for a site to be classified as positively selected. REL analysis identified four sites (208, 211, 218 and 219) in M1 under positive selection pressure. REL analysis tends to give better estimates on small datasets than SLAC and FEL. Sites 211, 218, and 219 were still selected when the bayes factor cut-off was increased from 50 to 200. Further analysis would be needed to determine if these sites actually are positively selected.