Patterns of polymorphism in genomic regions flanking three highly polymorphic surface antigens in Plasmodium falciparum

Many surface antigens of the human malaria parasite Plasmodium falciparum show extraordinary diversity, with different alleles being so divergent as to be unalignable in some coding regions. To better understand the population history and modes of selection on such loci, we sequenced genomic regions flanking the highly polymorphic genes merozoite surface protein-1, merozoite surface protein-2, and circumsporozoite protein, from reference isolates of P. falciparum. Diversity was much lower in genomic flanking regions than in the coding sequences. Average pairwise nucleotide diversity for these regions was 0.00088, similar to other genomic regions not thought to be evolving under balancing selection, suggesting against balancing selection acting on promoter regions of these genes. Most observed polymorphisms were singletons. A higher ratio of SNPs to indels than previously reported for P. falciparum was observed. An 11 bp repeat upstream of msp2 showed an intriguing pattern of polymorphism possibly suggestive of purifying selection on total allele length.