Stable allele frequency distribution of the polymorphic region of SURFIN(4.2) in Plasmodium falciparum isolates from Thailand

Abstract

Plasmodium falciparum SURFIN₄.₂ (PFD1160w) is a polymorphic protein expressed on the surface of parasite-infected erythrocytes. Such molecules are expected to be under strong host immune pressure, thus we analyzed the nucleotide diversity of the N-terminal extracellular region of SURFIN₄.₂ using P. falciparum isolates obtained from a malaria hypoendemic area of Thailand. The extracellular region of SURFIN₄.₂ was divided into four regions based on the amino acid sequence conservation among SURFIN members and the level of polymorphism among SURFIN₄.₂ sequences; N-terminal segment (Nter), a cysteine-rich domain (CRD), a variable region 1 (Var1), and a variable region 2 (Var2). Comparison between synonymous and non-synonymous substitutions, Tajima's D test, and Fu and Li's D* and F* tests detected signatures of positive selection on Var2 and to a lesser extent Var1, suggesting that these regions were likely under host immune pressure. Strong linkage disequilibrium was detected for nucleotide pairs separated by a distance of more than 1.5 kb, and 7 alleles among 19 alleles detected in 1988-1989 still circulated 14 years later, suggesting low recombination of the analyzed surf₄.₂ sequence region in Thailand. The allele frequency distribution of polymorphic areas in Var2 did not differ between two groups collected in different time points, suggesting the allele frequency distribution of this region was stable for 14 years. The observed allele frequency distribution of SURFIN₄.₂ Var2 may be fixed in Thai P. falciparum population as similar to the observation for P. falciparum merozoite surface protein 1, for which a stable allele frequency distribution was reported.