Qixin, Shai, and Mercedes’ new paper with collaborators Kathryn Tiedje and Karen Day at the University of Melbourne has just been published in Frontiers in Ecology and Evolution in the section Models in Ecology and Evolution. The paper shows how Plasmodium falcipuram malaria transmission systems can be more persistent when strains are under negative frequency dependent selection compared to neutrality.
In regions which have highly endemic malaria transmission, local populations of the Plasmodium falcipuram parasite exhibit a high diversity of var genes that encode the major surface antigen. Each parasite contains multiple copies from this large pool of var genes. This large combinatorial antigenic diversity enables the parasite to evade the host immune system. In previous work, Mercedes and her colleagues showed that negative frequency-dependent selection (NFDS) mediated by the acquisition of specific immunity by hosts structures the diversity of var gene repertoires, or strains, in a pattern of limiting similarity that is both non-random and non-neutral. They used a combination of stochastic agent-based models and network analyses to develop and test theoretical approaches for these complex adaptive systems.
In this paper, they compare how this malaria system responds to intervention efforts under two different scenarios. In the first scenario, strain diversity is assembled under (competition-based) selection with hosts having specific immunity to previously encountered strains. In the second scenario, strain diversity is assembled under a form of neutrality, where immunity depends only on the number but not the genetic identity of previous infections.
Mercedes and her colleagues find that the transmission system is considerably more persistent under negative frequency dependent selection, exhibiting a lower extinction probability despite comparable prevalence during intervention. For simulations that survive intervention, prevalence under specific immunity is lower than under neutrality, because the recovery of diversity is considerably slower than that of prevalence and decreased var gene diversity reduces parasite transmission. Despite lower overall diversity, NFDS is quickly restored after intervention constraining strain structure and maintaining patterns of limiting similarity important to parasite persistence.
These results suggest that intervention efforts will likely require longer times than the usual practice to eliminate P. falciparum populations in these highly endemic regions where strain diversity is shaped by negative frequency dependent selection. These results may also have implications for other ecological communities with non-neutral assembly processes involving frequency-dependence.
The paper can be found on the Frontiers in Ecology and Evolution website.