A study of genetic diversity in the gene encoding the circumsporozoite protein (CSP) of Plasmodium falciparum from different transmission areas - XVI. Asembo Bay Cohort Project

Ananias A. Escalante, Heather M. Grebert, Raul Isea, Ira F. Goldman, Leonardo Basco, Magda Magris, Sukla Biswas, Simon Kariuki, Altaf A. Lal

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

We have investigated the genetic diversity of the gene encoding the CS protein. A total of 75 complete and 96 partial sequences are studied. We find high levels of genetic polymorphisms as evidenced by 50 and 24 alleles at the Th2R and Th3R epitopes, respectively. Overall, we find that African isolates are more polymorphic as compared with parasites from other geographic regions. We conclude that the uneven geographic polymorphism may have an adverse impact on the effectiveness of vaccines based on this antigen alone. We find extensive polymorphism in the repeat allotypes, or RATs. In order to explore how the protein structure may impose restrictions in the number of repeats, we have simulated the stability of the structure of the tandem repeat region. Our analysis suggests that the protein structure may play an important role in the observed polymorphism in the number of CS repeats in Plasmodium falciparum. We explored the linkage and recombination events among the polymorphic sites. We found that putative recombination events overlap with linked sites. We discuss how this pattern is explained by the action of positive natural selection, where the recombination events detected are convergent mutations. We conclude that it is inappropriate to use linkage-recombination patterns on genes under positive selection for assessing the structure of parasite populations.

Original languageEnglish (US)
Pages (from-to)83-90
Number of pages8
JournalMolecular and Biochemical Parasitology
Volume125
Issue number1-2
DOIs
StatePublished - Jan 1 2002

Keywords

  • Circumsporozoite
  • Evolution repeats
  • Genetic diversity
  • Geographic variation
  • Intragenic recombination
  • Malaria
  • Plasmodium
  • Vaccine

ASJC Scopus subject areas

  • Parasitology
  • Molecular Biology

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