The extent of nucleotide polymorphism is highly variable across a 3-kb region on Plasmodium falciparum chromosome 2

Genomic nucleotide polymorphism in the virulent human malarial parasite Plasmodium falciparum was surveyed by sequencing a 3-kb region of chromosome 2 from 21 isolates, including the MSP4 and MSP5 genes. Extensive sequence polymorphism was observed in the coding regions of these genes and in the region downstream to MSP5, and the average pairwise divergence time of haplotypes in this region was estimated to be at least about 200,000 years. But nucleotide polymorphism was not found in the introns and was much reduced in the intergenic region. Over the entire region, nucleotide diversity was negatively correlated with a nucleotide content skewed toward thymine. Together with the previous evidence of limited nucleotide polymorphism in introns of P. falciparum, these data suggest the existence of a mechanism suppressing single-nucleotide polymorphism in regions of the P. falciparum genome with highly skewed nucleotide content.