The origin of Plasmodium falciparum in South America is controversial. Some studies suggest a recent introduction during the European colonizations and the transatlantic slave trade. Other evidence—archeological and genetic—suggests a much older origin. We collected and analyzed P. falciparum isolates from different regions of the world, encompassing the distribution range of the parasite, including populations from sub-Saharan Africa, the Middle East, Southeast Asia, and South America. Analyses of microsatellite and SNP polymorphisms show that the populations of P. falciparum in South America are subdivided in two main genetic clusters (northern and southern). Phylogenetic analyses, as well as Approximate Bayesian Computation methods suggest independent introductions of the two clusters from African sources. Our estimates of divergence time between the South American populations and their likely sources favor a likely introduction from Africa during the transatlantic slave trade.

Recent molecular exploration of the Plasmodium species circulating in great apes in Africa has revealed the existence of a large and previously unknown diversity of Plasmodium. For instance, gorillas were found to be infected by parasites closely related to Plasmodium falciparum, suggesting that the human malignant malaria agent may have arisen after a transfer from gorillas. Although this scenario is likely in light of the data collected in great apes, it remained to be ascertained whether P. falciparum-related parasites may infect other nonhuman primates in Africa. Using molecular tools, we here explore the diversity of Plasmodium species infecting monkeys in Central Africa. In addition to previously described Hepatocystis and Plasmodium species (Plasmodium gonderi and Plasmodium sp DAJ-2004), we have found one African monkey to be infected by a P. falciparum-related parasite. Examination of the nuclear and mitochondrial genomes of this parasite reveals that it is specific of nonhuman primates, indicating that P. falciparum-related pathogens can naturally circulate in some monkey populations in Africa. We also show that at least two distinct genetic entities of P. falciparum infect nonhuman primates and humans, respectively. Our discoveries bring into question the proposed gorilla origin of human P. falciparum.human malaria | laverania clade | parasite host transfer | cytochrome b | biological evolution U ntil very recently, only one species (Plasmodium reichenowi) was known to be a phylogenetic sister lineage of Plasmodium falciparum, the agent of malignant human malaria. These two species were the only known representatives of the subgenus Laverania (1). In 2009 and 2010, several studies have revealed the existence of a number of distinct phylogenetic species belonging to this subgenus and infecting chimpanzees, bonobos, and gorillas in Africa (2-6), drastically modifying our understanding of the evolution of the Laverania lineage, and P. falciparum in particular (7).Liu et al. (4) have proposed that the human strains of P. falciparum arose after a single gorilla-to-human transmission (4, 7). This scenario is based on the discovery of P. falciparum-related strains naturally circulating in lowland gorillas (2, 4, 6) that display greater genetic diversity than human strains (4). In contrast, no P. falciparum strains were found in wild chimpanzees or bonobos despite similar sampling efforts (4). Strains of P. falciparum had been found only in chimpanzees and bonobos living either in captivity or sanctuaries, with the possibility of a crossspecies infection from humans to them (2, 3). It, however, remains possible that P. falciparum-related strains circulate in wild chimpanzees and bonobos at a lower prevalence than in gorillas (8) and/or in geographic areas not yet explored. Given the propensity of Plasmodium parasites to switch hosts (e.g., the transfer of P. knowlesi from macaques to humans (9) and P. vivax and P. malariae between humans and New World monkeys; ref. 10), one cannot exclude that P. falciparum-r...