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Genetic variation and the recent worldwide expansion of Plasmodium falciparum.


Plasmodium falciparum, the agent of human malignant malaria, diverged from Plasmodium reichenowi, the chimpanzee parasite, about the time the human and chimpanzee lineages diverged from each other. The absence of synonymous nucleotide variation at ten loci indicates that the world populations of P. falciparum derive most recently from one single strain, or 'cenancestor,' which lived a few thousand years ago. Antigenic genes of P. falciparum (such as Csp, Msp-1, and Msp-2) exhibit numerous polymorphisms that have been estimated to be millions of years old. We have discovered in these antigenic genes short repetitive sequences that distort the alignment of alleles and account for the apparent old age of the polymorphisms. The processes of intragenic recombination that generate the repeats occur at rates about 10(-3) to 10(-2), several orders of magnitude greater than the typical mutational process of nucleotide substitutions. We conclude that the antigenic polymorphisms of P. falciparum are consistent with a recent expansion of the world populations of the parasite from a cenancestor that lived in tropical Africa a few thousand years ago.

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