Chromosome-wide SNPs reveal an ancient origin for Plasmodium falciparum

Abstract

The Malaria's Eve hypothesis, proposing a severe recent population bottleneck (about 3,000–5,000 years ago) of the human malaria parasite Plasmodium falciparum, has prompted a debate about the origin and evolution of the parasite^1,2,3,4,5,6. The hypothesis implies that the parasite population is relatively homogeneous, favouring malaria control measures. Other studies, however, suggested an ancient origin and large effective population size^5,7,8,9,10. To test the hypothesis, we analysed single nucleotide polymorphisms (SNPs) from 204 genes on chromosome 3 of P. falciparum. We have identified 403 polymorphic sites, including 238 SNPs and 165 microsatellites, from five parasite clones, establishing chromosome-wide haplotypes and a dense map with one polymorphic marker per ∼2.3 kilobases. On the basis of synonymous SNPs and non-coding SNPs, we estimate the time to the most recent common ancestor to be ∼100,000–180,000 years, significantly older than the proposed bottleneck. Our estimated divergence time coincides approximately with the start of human population expansion¹¹, and is consistent with a genetically complex organism able to evade host immunity and other antimalarial efforts.