Fig. 3.

Herpesvirus latent peptides that bind HLA have increased population differentiation. Estimates of F_ST were compared between latent and nonlatent genes and between HLA binding and nonbinding sites in each herpesvirus protein using a linear mixed model to determine differences in F_ST. (A) The posterior distribution for F_ST in genes expressed during latency or not is plotted for each virus. (B) Normalized F_ST, where virus-specific effects on F_ST were removed from F_ST estimates for each herpesvirus gene (Materials and Methods), was plotted for HLA binding and nonbinding regions of latent or nonlatent herpesvirus genes using either synonymous or nonsynonymous polymorphism. Significance was assessed by the proportion of MCMC iterations that overlap zero for the posterior distribution of the interaction effect between HLA binding and latent expression (${\beta }_{\mathit{HLA}:\mathit{Latent}}$ in SI Appendix, Eq. 2). (C) The difference between F_ST in HLA binding vs. nonbinding regions of each herpesvirus gene (ΔF_ST) was calculated for every herpesvirus protein:HLA allotype combination. All EBV and VZV latency proteins included in the model and the 10 HCMV latency proteins with the highest ΔF_ST values are plotted, with box color corresponding to ΔF_ST. Allotypes were clustered based on similarity in ΔF_ST values across latent genes. (D) Plotted is the posterior distribution of the difference between $u_{\mathit{Gene}:\mathit{HLA}}$ and $u_{\mathit{Gene}}$, which reflects the impact of HLA presentation on population structure of individual genes. Those with the 90% highest posterior density intervals that do not overlap zero are shaded with color. *P < 0.05; **P < 0.01.