The maintenance of strain structure in populations of recombining infectious agents
- 1 April 1996
- journal article
- Published by Springer Science and Business Media LLC in Nature Medicine
- Vol. 2 (4), 437-442
- https://doi.org/10.1038/nm0496-437
Abstract
Using mathematical models that combine population genetic and epidemiological processes, we resolve the paradox that many important pathogens appear to persist as discrete strains despite the constant exchange of genetic material. We show that dominant polymorphic determinants (that is, those that elicit the most effective immune responses) will be organized into nonoverlapping combinations as a result of selection by the host immune system, thereby defining a set of discrete independently transmitted strains. By analysing 222 isolates of Neisseria meningitidis, we show that two highly polymorphic epitopes of the outer membrane protein PorA exist in nonoverlapping combinations as predicted by this general framework. The model indicates that dominant polymorphic determinants will be in linkage disequilibrium, despite frequent genetic exchange, even though they may be encoded by several unlinked genes. This suggests that the detection of nonrandom associations between epitope regions can be employed as a novel strategem for identifying dominant polymorphic antigens.Keywords
This publication has 37 references indexed in Scilit:
- Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytesCell, 1995
- The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of plasmodium falciparum-infected erythrocytesCell, 1995
- Antigenic diversity and the transmission dynamics of Plasmodium falciparum: The clonality/sexuality debate revisitedParasitology Today, 1994
- Theoretical studies of the effects of heterogeneity in the parasite population on the transmission dynamics of malariaProceedings Of The Royal Society B-Biological Sciences, 1994
- Antigenic Diversity and the Transmission Dynamics of Plasmodium falciparumScience, 1994
- Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypesAIDS, 1993
- How clonal are bacteria?Proceedings of the National Academy of Sciences of the United States of America, 1993
- Rapid switching to multiple antigenic and adhesive phenotypes in malariaNature, 1992
- A clonal theory of parasitic protozoa: the population structures of Entamoeba, Giardia, Leishmania, Naegleria, Plasmodium, Trichomonas, and Trypanosoma and their medical and taxonomical consequences.Proceedings of the National Academy of Sciences of the United States of America, 1990
- HUMAN IMMUNITY TO THE MENINGOCOCCUSThe Journal of Experimental Medicine, 1969