As noted above, we condition the results presented here on a specific sequence alignment. As the question under consideration concerns the divergence of specific genes and proteins over a (presumably) long time scale, the capacity to generate reasonable alignments diminishes with increasing time of divergence between types, conditional on the rate of substitution. We find that for the hemagglutinin gene, a proportion of sequence alignments support the split of subtype B from subtype C after the split between subtypes A-H3N2 and B, in opposition to the topology enforced in our analysis. Hence, to some unknown degree, our analysis is necessarily biased by the choice of alignment. This suggests that improved dating can be found by integrating estimation procedures over an ensemble of alignments [19] .