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

• Main Authors: Naoko Sakihama, Masatsugu Kimura, Kenji Hirayama, Tozo Kanda, Kesara Na-Bangchang, Somchai Jongwutiwes, David Conway, Kazuyuki Tanabe
• Other Authors: Osaka Institute of Technology
• Format: Article
• Published: 2018
• Subjects: Biochemistry, Genetics and Molecular Biology
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/25345
• Institution: Mahidol University

The C-terminal, cysteine-rich 19 kDa 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 19 kDa domain is limited among parasite isolates, tertiary structure-dependent intramolecular associations between the 19 kDa 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 19 kDa 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.