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    Signatures of competition and strain structure within the major blood-stage antigen of Plasmodium falciparum in a local community in Ghana

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    Author
    Rorick, MM; Artzy-Randrup, Y; Ruybal-Pesantez, S; Tiedje, KE; Rask, TS; Oduro, A; Ghansah, A; Koram, K; Day, KP; Pascual, M
    Date
    2018-04-01
    Source Title
    Ecology and Evolution
    Publisher
    WILEY
    University of Melbourne Author/s
    Tiedje, Kathryn; Day, Karen
    Affiliation
    Microbiology and Immunology
    Metadata
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    Document Type
    Journal Article
    Citations
    Rorick, M. M., Artzy-Randrup, Y., Ruybal-Pesantez, S., Tiedje, K. E., Rask, T. S., Oduro, A., Ghansah, A., Koram, K., Day, K. P. & Pascual, M. (2018). Signatures of competition and strain structure within the major blood-stage antigen of Plasmodium falciparum in a local community in Ghana. ECOLOGY AND EVOLUTION, 8 (7), pp.3574-3588. https://doi.org/10.1002/ece3.3803.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/256159
    DOI
    10.1002/ece3.3803
    Abstract
    The concept of niche partitioning has received considerable theoretical attention at the interface of ecology and evolution of infectious diseases. Strain theory postulates that pathogen populations can be structured into distinct nonoverlapping strains by frequency-dependent selection in response to intraspecific competition for host immune space. The malaria parasite Plasmodium falciparum presents an opportunity to investigate this phenomenon in nature, under conditions of high recombination rate and extensive antigenic diversity. The parasite's major blood-stage antigen, Pf EMP1, is encoded by the hyperdiverse var genes. With a dataset that includes thousands of var DBLα sequence types sampled from asymptomatic cases within an area of high endemicity in Ghana, we address how var diversity is distributed within isolates and compare this to the distribution of microsatellite allelic diversity within isolates to test whether antigenic and neutral regions of the genome are structured differently. With respect to var DBLα sequence types, we find that on average isolates exhibit significantly lower overlap than expected randomly, but that there also exists frequent pairs of isolates that are highly related. Furthermore, the linkage network of var DBLα sequence types reveals a pattern of nonrandom modularity unique to these antigenic genes, and we find that modules of highly linked DBLα types are not explainable by neutral forces related to var recombination constraints, microsatellite diversity, sampling location, host age, or multiplicity of infection. These findings of reduced overlap and modularity among the var antigenic genes are consistent with a role for immune selection as proposed by strain theory. Identifying the evolutionary and ecological dynamics that are responsible for the nonrandom structure in P. falciparum antigenic diversity is important for designing effective intervention in endemic areas.

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