Inferring pandemic growth rates from sequence data

de Silva, Eric; Ferguson, Neil M.; Fraser, Christophe

The model is seeded with a starting sequence of arbitrary length-in this case, the full-length HA gene of one of the first US H1N1 influenza virus isolates A/California/04/ 09. The seed sequence is generation 0 at time t ¼ 0 and its offspring comprise generation 1 and time, t ¼ T g and their offspring generation 2 and time t ¼ 2T g and so on, where T g is the generation time. Rambaut et al. [17] find the HA gene to have mean rate of evolutionary change to be 5.72e 23 nucleotide substitutions (sub) per site per year (the highest of all the proteins, unsurprisingly, given its function in avoiding the immune system). This equals 1.57e 25 sub per site per day, which for a generation time of 2.6 days is 4.1e 25 sub per site per generation. In our simulation, we choose a mutation rate of 1.83e 24 sub per site per generation, faster than the estimate of Rambaut et al., as the substitution rate for many pathogens is expected to be faster at short time scales owing to the long-term effects of purifying selection [18] . Our findings were not very sensitive to the mutation rate (analysis not shown).