  Most antigenically novel and evolutionarily successful strains of seasonal
influenza A (H3N2) originate in East, South, and Southeast Asia. To understand
this pattern, we simulated the ecological and evolutionary dynamics of
influenza in a host metapopulation representing the temperate north, tropics,
and temperate south. Although seasonality and air traffic are frequently used
to explain global migratory patterns of influenza, we find that other factors
may have a comparable or greater impact. Notably, a region's basic reproductive
number ($R_0$) strongly affects the antigenic evolution of its viral population
and the probability that its strains will spread and fix globally: a 17-28%
higher $R_0$ in one region can explain the observed patterns. Seasonality, in
contrast, increases the probability that a tropical (less seasonal) population
will export evolutionarily successful strains but alone does not predict that
these strains will be antigenically advanced. The relative sizes of different
host populations, their birth and death rates, and the region in which H3N2
first appears affect influenza's phylogeography in different but relatively
minor ways. These results suggest general principles that dictate the spatial
dynamics of antigenically evolving pathogens and offer predictions for how
changes in human ecology might affect influenza evolution.
