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Persistent. After attaching to red blood cells, Plasmodium falciparum (yellow) enters the cell, where it differentiates into a gametocyte that is ready to be taken up by the mosquito.

New Clues to Malaria's Origin

Malaria has always plagued humans. But the disease probably didn't really take off until hunter-gatherers settled down to a more pastoral life. A new analysis of genetic variation in Plasmodium falciparum, the parasite causing the deadliest form of malaria, suggests that its numbers exploded once people started farming. The study is published in the 20 July issue of Science.

The origins of malaria have been debated for decades. Recently, the debate has intensified, because DNA analyses to reconstruct the parasite's past have resulted in very different conclusions. One early report suggested it evolved from a bird parasite once humans became farmers. Later, a more comprehensive look at the parasite's family tree concluded it evolved from a chimp parasite about 8 million years ago, about the same time that prehumans branched off the primate lineage.

To try to resolve this controversy, molecular parasitologist Dyann Wirth of the Harvard School of Public Health in Boston and her colleagues looked at the noncoding regions of eight parasite genes. These regions, called introns, mutate readily without harming the parasite; as a result, they accumulate differences that can be used to assess genetic diversity.

The researchers sequenced 25 introns from eight strains of P. falciparum. They found that just three base pairs differed between the strains. From that, they calculated that modern P. falciparum all trace their ancestry to a single small population that began to flourish between 9500 and 23,000 years ago--about the time when early hunters set up farming communities. That agricultural revolution increased population densities and probably led to more stagnant pools in which mosquitoes can breed--two factors favoring the spread of malaria, Wirth says. The results match that of another study, published in Science last month (ScienceNOW, 25 June).

"The implication, which I find convincing, is that virtually all of the existing sequence variation is of recent origin," says David Conway, a molecular parasitologist at the London School of Hygiene and Tropical Medicine. Some other researchers are skeptical. Austin Hughes from the University of South Carolina, Columbia, for example, will report in an upcoming Proceedings of the Royal Society that plenty of variation exists in the 23 P. falciparum genes his team studied. Hughes thinks the parasite was already widespread 300,000 years ago.

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