Abstract
BackgroundPlasmodium simium, a malaria parasite of non-human primates (NHP), was recently shown to cause zoonotic infections in humans in Brazil. We sequenced the P. simium genome to investigate its evolutionary history and to identify any genetic adaptions that may underlie the ability of this parasite to switch between host species.ResultsPhylogenetic analyses based on whole genome sequences of P. simium from humans and NHPs reveals that P. simium is monophyletic within the broader diversity of South American Plasmodium vivax, suggesting P. simium first infected NHPs as a result of a host switch of P. vivax from humans. The P. simium isolates show the closest relationship to Mexican P. vivax isolates. Analysis of erythrocyte invasion genes reveals differences between P. vivax and P. simium, including large deletions in the Duffy-binding protein 1 (DBP1) and reticulocyte-binding protein 2a genes of P. simium. Analysis of P. simium isolated from NHPs and humans revealed a deletion of 38 amino acids in DBP1 present in all human-derived isolates, whereas NHP isolates were multi-allelic.ConclusionsAnalysis of the P. simium genome confirmed a close phylogenetic relationship between P. simium and P. vivax, and suggests a very recent American origin for P. simium. The presence of the DBP1 deletion in all human-derived isolates tested suggests that this deletion, in combination with other genetic changes in P. simium, may facilitate the invasion of human red blood cells and may explain, at least in part, the basis of the recent zoonotic infections.
Highlights
Plasmodium simium, a malaria parasite of non-human primates (NHP), was recently shown to cause zoonotic infections in humans in Brazil
A phylogenetic tree constructed from 3181 of 1:1 orthologs of the annotated P. simium protein-coding genes with the orthologues of P. vivax, P. cynomolgi, P. coatneyi, P. knowlesi, P. malariae, P. falciparum, P. reichenowi and P. gallinaceum confirmed that P. simium is very closely related to P. vivax (Additional file 2: Figure S3)
Analysis of gene families revealed a P. simium gene repertoire largely similar to P. vivax (Additional file 1: Table S2; Additional file 2: Figure S4), the number of PIR genes in P. simium genome appear to be less than half the number of VIR genes in P. vivax
Summary
Plasmodium simium, a malaria parasite of non-human primates (NHP), was recently shown to cause zoonotic infections in humans in Brazil. There are currently eight species of malaria parasites known to cause disease in humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae (considered to be indistinguishable from P. brasilianum [1]), Plasmodium ovale curtisi, Plasmodium ovale wallikeri, Plasmodium knowlesi, Plasmodium cynomolgi and Plasmodium simium. The last three species are non-human primate (NHP) parasites that have recently been shown to infect humans [2,3,4]. Understanding how malaria parasites adapt to new hosts and new transmission environments allows the risks posed by novel zoonotic malaria outbreaks to be assessed
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