Allelic recombination and linkage disequilibrium within Msp-1 of Plasmodium falciparum, the malignant human malaria parasite.
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.
Sakihama
N
N
Laboratory of Biology, Osaka Institute of Technology, Ohmiya, Asahi-ku, Osaka 535-8585, Japan.
Kimura
M
M
Hirayama
K
K
Kanda
T
T
Na-Bangchang
K
K
Jongwutiwes
S
S
Conway
D
D
Tanabe
K
K
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008288:Malaria / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic / Q000235:genetics; D013785:Thailand
D020066:Merozoite Surface Protein 1