Malaria's Recent Origins

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Science  20 Jul 2001:
Vol. 293, Issue 5529, pp. 389
DOI: 10.1126/science.293.5529.389g


Despite the risk of hemopathology, mutations within the human gene encoding glucose-6-phosphate dehydrogenase are seen in more than 400 million African and Mediterranean people. The mutations have long been suspected to have become so common because the resulting hemolysis of mature red blood cells inhibits the establishment of the malaria parasite Plasmodium falciparum. Tishkoff et al. (p. 455; see the Perspective by Luzzatto and Notaro) have identified three highly variable markers at this locus that provide direct evidence of this relation and that date the origin of malaria to about 6500 years in Africa and to about 3300 years ago in the Mediterranean. Why is P. falciparum so variable in the protein sequences affected by host responses and drugs and yet shows almost no variation in housekeeping genes? Volkman et al. (p. 482; see the news story by Pennisi) sequenced 25 introns from housekeeping regions of eight parasite isolates, but only found eight single nucleotide polymorphisms, most of which were in regions of microsatellite polymorphism. These data hint not only to a recent, possibly single progenitor of P. falciparum, but also to a high mutation rate within the microsatellite repeats.