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Ape Parasite Genomes Suggest African Origin for Human Malaria-Causing Plasmodium Vivax

NEW YORK (GenomeWeb) – Plasmodium vivax parasites that infect humans have highly similar genomes to parasites that infect apes, according to a new analysis.

P. vivax causes more than 8 million cases of malaria in humans each year, mostly in Southeast Asia and South America. P. vivax was thought to have emerged in Asia until similar parasites were uncovered in wild chimpanzees and gorillas. This instead suggested an African origin for the parasite, even though P. vivax is largely absent from humans in Africa, due to a genetic variant present among people there.

"Chimpanzees, bonobos, and gorillas all harbor parasites that are close relatives of human P. vivax, but to date our knowledge of these parasites has been limited to a small number of gene fragments," co-senior author Beatrice Hahn from the University of Pennsylvania said in a statement.

She and her colleagues compared the coding regions of P. vivax-like parasites isolated from chimpanzees, gorillas, and humans. As they reported in the Proceedings of the National Academy of Sciences today, they found that P. vivax isolates from African apes and those found in humans from Asia and South America share nearly identical core genomes. This, they said, supports the notion that a P. vivax ancestor once infected both humans and apes in Africa.

The researchers used a nested PCR approach to screen for Plasmodium in leftover blood samples taken from chimpanzees during routine health checks at a center in Cameroon. From this, they identified, amplified, and sequenced the full genomes of two ape P. vivax parasites.

The researchers also amassed partial genome sequencing data from P. vivax isolated from two chimpanzees from Côte d'Ivoire and from a western lowland gorilla from Cameroon, as well as additional P. vivax reads they identified from a database of sequences found in apes with malaria.

When they compared the ape sequences to two human P. vivax reference genomes as well as seven other P. vivax strains isolated from humans, the researchers found that the chimpanzee strains were more genetically diverse. The two sequenced chimpanzee strains differed from each other at 0.6 percent of sites and from the two human references strains at an average 2.2 percent of sites.

Through a phylogenetic analysis, the researchers found the human P. vivax strains formed a monophyletic lineage that either falls within the ape lineage or as a sister group to the ape lineage.

Despite this close relationship, the researchers noted that the ape parasites have about 10 times the neutral genetic diversity as the human parasites, while the human parasites have increased numbers of nonsynonymous nucleotide polymorphisms. This could reflect that the human parasites experienced a severe genetic bottleneck, followed by population expansion. That bottleneck, the researchers said, could have occurred when an ancestral P. vivax made the leap from infecting apes to infecting humans or, if the ancestral parasite infected both, when P. vivax migrated out of Africa with humans and the population may have undergone rapid population growth as it spread outside Africa.

The researchers also found no host-specific barriers affecting red blood cell invasion. They did find that three reticulocyte-binding protein, or RBP, genes that underwent pseudogenization in the human-infecting parasites. But, a series of binding studies showed no differences in binding to human, chimpanzee, or gorilla erythrocytes, indicating that, perhaps, there are no host-specific barriers.

It's unclear, they added, whether the populations have become separate species, which could have ramifications for malaria eradication campaigns.

"Since parasites very similar to human P. vivax infect a large number of wild-living apes, we need to be aware that there could be spillover into humans," co-senior author Paul Sharp from the University of Edinburgh said in a statement.