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

Qixin He, Shai Pilosof, Kathryn E. Tiedje, Shazia Ruybal-Pesántez, Yael Artzy-Randrup, Edward B. Baskerville, Karen P. Day and Mercedes Pascual ()
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Qixin He: University of Chicago
Shai Pilosof: University of Chicago
Kathryn E. Tiedje: Bio21 Institute/University of Melbourne
Shazia Ruybal-Pesántez: Bio21 Institute/University of Melbourne
Yael Artzy-Randrup: University of Amsterdam
Edward B. Baskerville: University of Chicago
Karen P. Day: Bio21 Institute/University of Melbourne
Mercedes Pascual: University of Chicago

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Pathogens compete for hosts through patterns of cross-protection conferred by immune responses to antigens. In Plasmodium falciparum malaria, the var multigene family encoding for the major blood-stage antigen PfEMP1 has evolved enormous genetic diversity through ectopic recombination and mutation. With 50–60 var genes per genome, it is unclear whether immune selection can act as a dominant force in structuring var repertoires of local populations. The combinatorial complexity of the var system remains beyond the reach of existing strain theory and previous evidence for non-random structure cannot demonstrate immune selection without comparison with 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.

Date: 2018
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DOI: 10.1038/s41467-018-04219-3

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