Changes in genetic diversity and the McDonald-Kreitman related index (MKR) for varying strengths of strain competition and antigenic mutation rates.

<p><b>(A)</b> Mean pairwise genetic diversity π is measured as the mean distance, measured in years, for the coalescence of random pairs of contemporaneous samples in a tree. Diversity measurement is capped by twice the simulation run length which amounts to 240 years. <b>(B)</b> The MKR is measured as the ratio between the trunk antigenic mutation rate (fixed) and the sidebranches antigenic mutation rate. Evidence of positive selection is observed when the MKR index is significantly above one, and negative selection when it is significantly below one. Areas of strong positive selection are associated with lower genetic diversity as a small subset of the population contributes to long term viral evolution. Strong negative selection is associated with disruptive selection maintained by existing strains. <b>(C)</b> Diversity for varying strengths and directions of selection as measured by the MKR index. Diversity decreases with stronger positive selection <i>ρ</i> = −0.85 (Pearson's correlation right of dotted line), and increases for stronger negative selection <i>ρ</i> = −0.28. The harmonic mean of the prevalence is also strongly correlated with genetic diversity <i>ρ</i> = 0.76 (heat map). <b>(D)</b> Typical trees for varying strengths of strain competition and antigenic mutation rate. Effective competition combined with a limited availability of antigenic mutations results in narrower trees with lower pairwise diversity. This figure was parameterized to use R0 = 3 and a population size of 50M to limit stochastic extinctions for a large parameter range (see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1003104#s4" target="_blank">methods</a> for full description of epidemiological parameters).