NYMC Faculty Publications
DOI
10.1073/pnas.1613018114
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
First Page
E4103
Last Page
E4111
Document Type
Article
Publication Date
5-1-2017
Department
Medicine
Abstract
Existing theory on competition for hosts between pathogen strains has proposed that immune selection can lead to the maintenance of strain structure consisting of discrete, weakly overlapping antigenic repertoires. This prediction of strain theory has conceptual overlap with fundamental ideas in ecology on niche partitioning and limiting similarity between coexisting species in an ecosystem, which oppose the hypothesis of neutral coexistence. For Plasmodium falciparum, strain theory has been specifically proposed in relation to the major surface antigen of the blood stage, known as PfEMP1 and encoded by the multicopy multigene family known as the var genes. Deep sampling of the DBLalpha domain of var genes in the local population of Bakoumba, West Africa, was completed to define whether patterns of repertoire overlap support a role of immune selection under the opposing force of high outcrossing, a characteristic of areas of intense malaria transmission. Using a 454 high-throughput sequencing protocol, we report extremely high diversity of the DBLalpha domain and a large parasite population with DBLalpha repertoires structured into nonrandom patterns of overlap. Such population structure, significant for the high diversity of var genes that compose it at a local level, supports the existence of "strains" characterized by distinct var gene repertoires. Nonneutral, frequency-dependent competition would be at play and could underlie these patterns. With a computational experiment that simulates an intervention similar to mass drug administration, we argue that the observed repertoire structure matters for the antigenic var diversity of the parasite population remaining after intervention.
Recommended Citation
Day, K., Artzy-Randrup, Y., Tiedje, K., Rougeron, V., Chen, D. S., Rask, T., Rorick, M., Migot-Nabias, F., Deloron, P., Luty, A., & Pascual, M. (2017). Evidence of Strain Structure in Plasmodium falciparum var Gene Repertoires in Children from Gabon, West Africa. Proceedings of the National Academy of Sciences of the United States of America, 114 (20), E4103-E4111. https://doi.org/10.1073/pnas.1613018114
Publisher's Statement
Originally published in Proceedings of the National Academy of Sciences of the United States of America, 114 (20), E4103-E4111.
Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.
