Networks of genetic similarity reveal non-neutral processes shape strain structure inPlasmodium falciparum

Abstract

AbstractPathogens compete for hosts through patterns of cross-protection conferred by immune responses to antigens. InPlasmodium falciparummalaria, thevarmultigene family encoding for the major blood-stage antigenPfEMP1 has evolved enormous genetic diversity through ectopic recombination and mutation. With 50-60vargenes per genome, it is unclear whether immune selection can act as a dominant force in structuringvarrepertoires of local populations. The combinatorial complexity of thevarsystem remains beyond the reach of existing strain theory, and previous evidence for non-random structure cannot demonstrate immune selection without comparison to neutral models. We develop two neutral models that encompass malaria epidemiology but exclude competitive interactions between parasites. These models, combined with networks of genetic similarity, reveal non-neutral strain structure in both simulated systems and an extensively sampled population in Ghana. The unique population structure we identify underlies the large transmission reservoir characteristic of highly endemic regions in Africa.