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Phylogenetic Study Finds Human Malaria Originated In Chimps

NEW YORK (GenomeWeb News) – Based on their phylogenetic analysis, an international research team has concluded that the human malaria parasite Plasmodium falciparum originated from P. reichenowi, a species carried by chimpanzees.

The researchers found eight new P. reichenowi isolates in chimpanzees from Cameroon and the Ivory Coast and used phylogenetic analyses to compare these with malaria parasites from humans and other animals. Their results suggest that the human parasite P. falciparum is actually derived from the chimpanzee parasite — a finding that's at odds with the co-speciation hypothesis that says the parasites evolved from a common ancestor in parallel in chimps and humans.

"Instead of evolving together along individual lineages, as we previously hypothesized, we are debunking that hypothesis," co-author Brian Pike, director of laboratory sciences for the Global Viral Forecasting Initiative, told GenomeWeb Daily News. "Instead, it's clear that the human parasite is a derivative of the chimp parasite."

The research, which appeared online last night in the Proceedings of the National Academy of Sciences, suggests the malaria parasite jumped species from chimpanzees to humans in a single event that occurred between roughly 10,000 and a few million years ago.

P. falciparum is the most virulent and deadly human malaria parasite, causing roughly 85 percent of malaria cases.

Previous research demonstrated that the chimpanzee parasite P. reichenowi is more closely related to the P. falciparum than any other Plasmodium species, Pike explained. And some genetic studies appeared to support the idea that P. reichenowi and P. falciparum arose through co-speciation from a common ancestor.

But until now, just one P. reichenowi isolate was available, Pike and his co-authors noted, making it difficult to draw many conclusions about Plasmodium relationships.

For the latest study, he and his co-workers managed to track down eight more P. reichenowi isolates in Cameroon and the Ivory Coast after sampling roughly 100 animals at different animal sanctuaries. Because Plasmodium infection in chimpanzees is transient, as it is in humans, Pike explained, finding the isolates took time and persistence.

Next, the team amplified P. reichenowi sequences for the mitochondrial gene cytB, the apicoplast gene clpC, and a nuclear gene coding for 18S ribosomal DNA.

They then did separate phylogenetic analyses for each gene fragment, comparing the P. reichenowi isolates with four human malaria parasites (P. falciparum, P. vivax, P. malariae, and P. ovale), two African rodent parasites (P. berghei, P. yoelli), and a parasite that infects chickens (P. gallinaceum).

Their results suggest that P. reichenowi and P. falciparum form a monophyletic group that's distinct from the other Plasmodium species tested, with P. falciparum forming one branch of the P. reichenowi tree.

And in contrast to P. falciparum, which tends to have relatively few polymorphisms, the team found a great deal of genetic diversity within P. reichenowi, including many synonymous changes. That is consistent with the notion that P. falciparum evolved from P. reichenowi after the chimpanzee strain crossed into humans rather than springing up in parallel in each species.

While it's difficult to pin down exactly when this happened, the researchers estimated that the species diverged between about 10,000 years ago and two to three million years ago.

Despite the advances made so far, there's still a lot to be learned about the biology and evolutionary history of malaria parasites, Pike said. By continuing to find and compare human and chimpanzee parasites, the team hopes to gain insights into everything from host adaptation to potential targets for malaria treatments and vaccines. And, Pike noted, such studies may also reveal why P. falciparum is so malignant for humans.

Down the road, malaria genome sequencing may also be employed to gain a more complete view of the parasites' genetics. "In this day and age, [genome sequencing] is sort of the next logical step," Pike said.

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