Figure 6

Timeline of adaptation to human-to-human transmission for the influenza A PB2 protein. Using the H2H characteristic variant pattern (see Fig. 4), we produced signatures for each available human sequence isolated before 1970, and arranged them in chronological order. The signature columns show the residues observed at each of the characteristic sites, in the order given in Figure 4. Each signature is annotated with subtype, year and country of isolation, and isolate name. The first and the last pattern of the alignment are the consensus signatures for avian and human-to-human transmissible sequences respectively. Avian characteristic variants are shown on a dark blue background, human characteristic variants on a yellow background, and all other variants are on white. Red horizontal lines indicate the start of the 1957 and 1968 pandemics, which introduced the H2N2 and H3N2 subtypes respectively. The GenPept accession numbers for all sequences used are listed in Table S1 in Additional file 1.