Population genetic analysis of the Plasmodium falciparum erythrocyte binding antigen-175 (eba-175) gene

The Plasmodium falciparum erythrocyte binding antigen-175 gene (eba-175) has highly divergent allelic segments (Cseg and Fseg) in one part of the gene (region III), but only a small number of single nucleotide polymorphisms (SNPs) in the rest of the sequence. Here, evidence for the possible importance of the Cseg/Fseg dimorphism was sought in a molecular population genetic analysis of the gene. First, allele frequency distributions were determined for the Cseg/Fseg dimorphism and five SNPs in a sample of five populations in Africa. The inter-population variance in frequencies was higher for Cseg/Fseg (F(ST)=0.18) than for the SNPs (F(ST) values from 0.03 to 0.10), but these values were entirely dependent on the inclusion of one particularly divergent population (Sudan). Second, linkage disequilibrium was measured among the intragenic loci. There was the expected trend of declining linkage disequilibrium with increasing molecular distance, but it is notable that the Cseg allele was in absolute linkage disequilibrium with the two flanking SNPs, whereas the Fseg allele was associated with a broader range of SNP haplotypes. Finally, there was no association between the Cseg/Fseg alleles of eba-175 in parasites and the M/N alleles of the glycophorin A erythrocyte receptor in the human subjects.