Zoonotic origin of the human malaria parasite Plasmodium malariae from African apes

The human parasite Plasmodium malariae has relatives infecting African apes ( Plasmodium rodhaini ) and New World monkeys ( Plasmodium brasilianum ), but its origins remain unknown. Using a novel approach to characterise P. malariae -related sequences in wild and captive African apes, we found that this group comprises three distinct lineages, one of which represents a previously unknown, highly divergent species infecting chimpanzees, bonobos and gorillas across central Africa. A second ape-derived lineage is much more closely related to the third, human-infective lineage P. malariae , but exhibits little evidence of genetic exchange with it, and so likely represents a separate species. Moreover, the levels and nature of genetic polymorphisms in P. malariae indicate that it resulted from the zoonotic transmission of an African ape parasite, reminiscent of the origin of P. falciparum . In contrast, P. brasilianum falls within the radiation of human P. malariae , and thus reflects a recent anthroponosis. Plasmodium malariae is a cause of malaria in humans and related species have been identified in non-human primates. Here, the authors use genomic analyses to establish that human P. malariae arose from a host switch of an ape parasite whilst a species infecting New World monkeys can be traced to a reverse zoonosis.