BACKGROUND: Plasmodium 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.
RESULTS: Phylogenetic 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.
CONCLUSIONS: Analysis 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.
Bibliographical noteFunding Information:
The work was supported financially by the King Abdullah University of Science and Technology (KAUST) through the baseline fund BRF1020/01/01 to AP and BAS/1/1056-01-01 to STA, and the Award No. URF/1/1976-25 from the Office of Sponsored Research (OSR). The field work in the Atlantic Forest and laboratory analysis in Brazil received financial support from the Secretary for Health Surveillance of the Ministry of Health through the Global Fund (agreement IOC-005-Fio-13), Programa Nacional de Excelência (PRONEX) and contract 407873/2018-0 of the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), the Fundação de Amparo à Pesquisa do Estado de Minas Gerais (Fapemig CBB-APQ-02620-15) and the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Faperj), Brazil. CNPq supports CFAB, CTDR, MFFC, PB and RLO, with a research productivity fellowship. CTDR (CNE: E-26/202.921/2018), MFFC, PB and RLO are also supported by Faperj as Cientistas do nosso estado. AdP-C was supported by a postdoctoral fellowship from the Faperj and DAMA by a fellowship from the CGZV-SVS (Brazilian Ministry of Health) TED 49/2018 grant. SF was supported by a Wellcome Seed Award in Science to DCJ (208965/Z/17/Z).
We thank Prof. Xin-zhuan Su at the National Institute of Allergy and Infectious Diseases, NIH, for invaluable help in obtaining the parasite gDNA from the BEI Resources; Sidnei Silva and Graziela Zanini, for assistance on the parasitological diagnosis of the human samples; Aline Lavigne and Larissa Gomes for undertaking the PCR for P vivax ; Alcides Pissinatti and Silvia Bahadian Moreira for the facilities provided at the Primate Centre of Rio de Janeiro; Orzinete Rodrigues Soares for non-human primates? blood slides?; Marcelo Quintela, Waldemir Paix?o Vargas, Carlos Alberto C. da Silva, Alexandre B. de Souza, Vicente Klonowski, Romenique L. Ara?jo, Luis R. Nogueira, Fernando Barreto, Ana L. Quijada, Luiz P.P. Silva, Gelson Medeiros, Adilson B. Ramos, Marcilene B. Ramos, Carlos A.A. J?nior, Paulo G. Barbosa, S?rgio F. Fragoso, Adilson R. Silva, Cec?lia Cronemberger, Marcelo Rheingantz, Leonardo Nascimento and Jo?o Marins for the field support; Grupo T?cnico de Vigil?ncia de Arboviroses (GT-Arbo ? Brazilian Ministry of Health) for field and material supports; and Cassio Leonel Peterka from The Brazilian Ministry of Health for malaria epidemiological data. The following reagent was obtained through BEI Resources, NIAID, NIH: Plasmodium simium , Strain Howler, MRA-353, contributed by William E. Collins. We thank Kieran Samuk for assistance with pixy, Richard Carter for invaluable discussion and comment on previous versions of this manuscript, and Tony Holder for critical reading of the manuscript.
© 2021, The Author(s).
- Comparative genomics
- Plasmodium simium
- Plasmodium vivax