TY - JOUR T1 - The genome of the zoonotic malaria parasite <em>Plasmodium simium</em> reveals adaptations to host-switching JF - bioRxiv DO - 10.1101/841171 SP - 841171 AU - Tobias Mourier AU - Denise Anete Madureira de Alvarenga AU - Abhinav Kaushik AU - Anielle de Pina-Costa AU - Francisco J. Guzmán-Vega AU - Olga Douvropoulou AU - Qingtian Guan AU - Sarah Forrester AU - Filipe Vieira Santos de Abreu AU - Cesare Bianco Júnior AU - Julio Cesar de Souza Junior AU - Zelinda Maria Braga Hirano AU - Alcides Pissinatti AU - Silvia Bahadian Moreira AU - Maria de Fátima Ferreira-da-Cruz AU - Ricardo Lourenço de Oliveira AU - Stefan T. Arold AU - Daniel C. Jeffares AU - Patrícia Brasil AU - Cristiana Ferreira Alves de Brito AU - Richard Culleton AU - Cláudio Tadeu Daniel-Ribeiro AU - Arnab Pain Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/11/14/841171.abstract N2 - Plasmodium simium, a malaria parasite of non-human primates in the Atlantic forest region of Brazil was recently shown to cause zoonotic infection in humans in the region. Phylogenetic analyses based on the whole genome sequences of six P. simium isolates infecting 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 from humans carrying P. vivax. We provide molecular evidence that the current zoonotic infections of people have likely resulted from multiple independent host switches, each seeded from a different monkey infection. Very low levels of genetic diversity within P. simium genomes and the absence of P. simium-P. vivax hybrids suggest that the P. simium population emerged recently and has subsequently experienced a period of independent evolution in Platyrrhini monkeys. We further find that Plasmodium Interspersed Repeat (PIR) genes, Plasmodium Helical Interspersed Subtelomeric (PHIST) genes and Tryptophan-Rich Antigens (TRAg) genes in P. siumium are genetically divergent from P. vivax 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 in P. simium. Genotyping of P. simium isolates from non-human primates (NHPs) and zoonotic human infections showed that a precise deletion of 38 amino acids in DBP1 is exclusively present in all human infecting isolates, whereas non-human primate infecting isolates were polymorphic for the deletion. We speculate that these deletions in the parasite-encoded key erythrocyte invasion ligands and the additional rapid genetic changes have facilitated zoonotic transfer to humans. Non-human primate malaria parasites can be considered a reservoir of potential infectious human parasites that must be considered in any attempt of malaria elimination. The genome of P. simium will thus form an important basis for future functional characterizations on the mechanisms underlying malaria zoonosis. ER -