Positive Diversifying Selection on the <i>Plasmodium falciparum</i> <i>surf_4.1</i> Gene in Thailand

ABSTRACT

<i>Plasmodium falciparum</i> SURFIN_4.1 is a type I transmembrane protein thought to locate on the merozoite surface and to be responsible for a reversible adherence to the erythrocyte before invasion. In this study, we evaluated <i>surf_4.1</i> gene segment encoding extracellular region for polymorphism, the signature of positive selection, the degree of linkage disequilibrium, and temporal change in allele frequency distribution in <i>P. falciparum</i> isolates from Thailand in 1988–89, 2003, and 2005. We found that SURFIN_4.1 is highly polymorphic, particularly at the C-terminal side of the variable region located just before a predicted transmembrane region. A signature of positive diversifying selection on the variable region was detected by multiple tests and, to a lesser extent, on conserved N-terminally located cysteine-rich domain by Tajima’s <i>D</i> test. Linkage disequilibrium between sites over a long distance (> 1.5 kb) was detected, and multiple SURFIN_4.1 haplotype sequences detected in 1988/89 still circulated in 2003. Few of the single amino acid polymorphism allele frequency distributions were significantly different between the 1988/89 and 2003 groups, suggesting that the frequency distribution of SURFIN_4.1 extracellular region remained stable over 14 years.