The parasite that causes the deadliest form of malaria in humans was not transmitted by chimpanzees.
A wide-ranging study of malaria parasites in apes suggests that the species responsible for most cases of the disease in humans, Plasmodium falciparum, originated in gorillas — not, as was previously thought, in chimpanzees. Moreover, the researchers conclude, the parasite may have made the jump between species just once.
Of the five species of mosquito-borne parasite that cause malaria in humans, P. falciparum is by far the most common, causing hundreds of millions of cases of malaria and more than one million deaths per year. Understanding the parasite's origins will, researchers hope, help to inform medical strategies for tackling the disease.
Until now, scientists believed P. falciparum 's closest relative to be P. reichenowi, a parasite of chimpanzees (Pan troglodytes), but studies were limited to a few apes, many of them from captive populations. Whether wild populations were acting as natural reservoirs for Plasmodium species was not known.
The latest study, led by Beatrice Hahn of the University of Alabama at Birmingham and published today in Nature1, took in wild populations of chimpanzees, bonobos and gorillas from across sub-Saharan Africa to analyse the genes of ape parasites related to P. falciparum.
The team used faecal samples from specimen banks built up to investigate the evolution of HIV, including 1,827 from chimpanzees, 803 from gorillas and 107 from bonobos. They then sequenced the Plasmodium DNA found in the samples, looking particularly at DNA from mitochondria, the cells' energy factories.
They found high levels of malarial infection among chimpanzees and western gorillas (Gorilla gorilla), populations of which act as natural reservoirs for Plasmodium species, but no infections among eastern gorillas (Gorilla beringei) or bonobos (Pan paniscus).
The team used the mitochondrial DNA sequences to produce phylogenetic trees, which indicate relationships between organisms on the basis of DNA.
The researchers' analyses reveal that the apes were infected with at least nine species of Plasmodium, three of which are new to science. With one exception, the parasitic species were all very closely related, belonging to the subgenus Laverania, and were highly host-specific.
The P. falciparum samples from humans included in the study were most closely related to parasites that infected western gorillas in Cameroon, the Central African Republic and the Republic of the Congo, and is likely to have originated from a single transmission event.
Daniel Jeffares, an evolutionary biologist at University College London, describes the findings as "striking". He adds, "in terms of our understanding of parasites, this paper is a game-changer."
"It's a fascinating evolutionary question to ask where these human pathogens came from," says evolutionary biologist Paul Sharp of the University of Edinburgh, UK, who worked on the study. "We're now wondering whether a cross-species jump like this could happen again in the future."
However, Jeffares says that confirmation of a one-off event would require the analysis of more P. falciparum samples than were included in the study.
Sharp says that the group's samples are representative of the species as a whole because genetic diversity is low in P. falciparum compared with the diversity of Plasmodium species in apes. But Jeffares argues that low diversity in P. falciparum is a myth based on out-of-date references. "More recent papers show there is quite a lot of diversity in different areas. Maybe if you looked harder you would find multiple origins," he says.
If P. falciparum did make the jump to humans in a single event, this, and the other relationships revealed by the research, suggests that interspecies transmission is rare, which could bode well for attempts to eradicate malaria. If P. falciparum was successfully wiped out, Jeffares says, it could be hundreds of thousands of years before another parasite was transmitted from apes. However, Sharp wonders whether that would "simply open up a niche for another Plasmodium parasite to jump into humans".
The study could help scientists to pinpoint the genetic changes that allowed the parasite to infect humans. Jeffares says that it would be relatively simple and inexpensive to sample entire genomes of P. falciparum and its close relatives. "You could look throughout the whole genome and find out where rapid evolution has been taking place," he says.
Liu, W. et al. Nature 467, 420-425 (2010).
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Milton, J. Human malarial parasite came from gorillas. Nature (2010). https://doi.org/10.1038/news.2010.486