Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum, the malignant human malaria parasite

Gene. 1999 Apr 1;230(1):47-54. doi: 10.1016/s0378-1119(99)00069-4.

Abstract

The C-terminal, cysteine-rich 19kDa domain of merozoite surface protein-1 (MSP-1) of Plasmodium falciparum is a target of the host's humoral immunity and thus a malaria vaccine candidate. Although variation in the 19kDa domain is limited among parasite isolates, tertiary structure-dependent intramolecular associations between the 19kDa domain and other parts of MSP-1 are suggested to be involved in immune evasion by allowing competitive binding of protective and non-protective antibodies directed to their epitopes, which are conformationally in close proximity but separated at the primary structure. Since allelic recombination can account for the major variability of the Msp-1 gene, we examined whether linkage disequilibrium occurs between polymorphic loci in the 5'- and the 3'-region, the latter encoding the 19kDa domain. From 184 Thai field isolates, we selected 69 isolates with a single allelic type in six variable blocks of Msp-1 as determined by PCR-based allelic typing. All the isolates showed no evidence of recombination in blocks 6 to 16, whereas recombination was apparent in blocks 2 to 6. Sequencing of the 3'-region revealed two potential recombination sites in block 17. Strong linkage disequilibrium was seen between polymorphic loci in the 5'- and 3'-regions. The strength of this disequilibrium did not correlate with distance between loci. We discuss the possible role of epistatic selection on particular association types (haplotypes) of Msp-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Haplotypes
  • Humans
  • Linkage Disequilibrium / genetics*
  • Malaria / parasitology
  • Merozoite Surface Protein 1 / genetics*
  • Merozoite Surface Protein 1 / immunology
  • Molecular Sequence Data
  • Plasmodium falciparum / genetics*
  • Plasmodium falciparum / metabolism
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Recombination, Genetic / genetics
  • Thailand

Substances

  • Merozoite Surface Protein 1

Associated data

  • GENBANK/AB016616
  • GENBANK/AB016617
  • GENBANK/AB016618