The genome of the zoonotic malaria parasite Plasmodium simium reveals adaptations to host-switching

Abstract

SummaryPlasmodium simium, a malaria parasite of non-human primates in the Atlantic forest region of Brazil was recently shown to cause zoonotic infections in humans. Phylogenetic analyses based on the whole genome sequences of six P. simium isolates from humans and two isolates from brown howler monkeys revealed that P. simium is monophyletic within the broader diversity of South American Plasmodium vivax, consistent with the hypothesis that P. simium first infected non-human primates as a result of a host-switch of P. vivax from humans. Very low levels of genetic diversity within P. simium and the absence of P. simium-P. vivax hybrids suggest that the P. simium population emerged recently with a subsequent period of independent evolution in Platyrrhini monkeys. We find that Plasmodium Interspersed Repeat (PIR) genes, Plasmodium Helical Interspersed Subtelomeric (PHIST) genes and Tryptophan-Rich Antigen (TRAg) genes in P. simium are divergent from P. vivax orthologues and are enriched for non-synonymous single nucleotide polymorphisms, consistent with the rapid evolution of these genes. Analysis of genes involved in erythrocyte invasion revealed several notable differences between P. vivax and P. simium, including large deletions within the coding region of the Duffy Binding Protein 1 (DBP1) and Reticulocyte Binding Protein 2a (RBP2a) genes of P. simium. Sequence analysis of P. simium isolates from non-human primates (NHPs) and zoonotic human infections revealed a deletion of 38 amino acids in DBP1 present in all human-derived isolates, whereas NHP isolates were multi-allelic at this locus. We speculate that these deletions in key erythrocyte invasion ligands along with other significant genetic changes may have facilitated zoonotic transfer to humans. NHPs are a reservoir of parasites potentially infectious to humans that must be considered in malaria eradication efforts. The P. simium genome is an important resource for understanding the mechanisms of malaria parasite zoonoses.