Journal article

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

Qixin He, Shai Pilosof, Kathryn E Tiedje, Shazia Ruybal-Pesantez, Yael Artzy-Randrup, Edward B Baskerville, Karen P Day, Mercedes Pascual



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 mod..

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Awarded by Fogarty International Center at the National Institutes of Health


Funding Acknowledgements

This research was supported by the Fogarty International Center at the National Institutes of Health [Program on the Ecology and Evolution of Infectious Diseases (EEID), Grant number: R01-TW009670]. S.P. was supported by a James S. McDonnell Foundation 21st Century Science Initiative-Postdoctoral Program in Complexity Science-Complex Systems Fellowship Award and by a Fulbright Fellowship from the U.S. Department of State. We thank the participants, communities, and the Ghana Health Service in BD, Ghana, for their willingness to participate in this study. We also thank the personnel at the Navrongo Health Research Centre for sample collection and parasitological assessment/expertise. We are grateful to Abraham R. Oduro, Anita Ghansah, and Kwadwo Koram for their helpful input related to the field study, to Gerry Tonkin-Hill for the development of the Illumina sequencing, cleaning, and clustering pipelines, and to Michael F. Duffy and Andrew P. Dobson for their insightful comments on an earlier version of the manuscript. We appreciate the support of the University of Chicago through computational resources of the Midway cluster.