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

Abstract

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.

Primate malarias as a model for cross-species parasite transmission

“…Historical DNA from pre-eradication Spain suggest a recent introduction and close relationship between historical Southern European P. vivax and modern South American P. vivax ( van Dorp et al, 2020 ). This is consistent with a host switch of historical P. vivax into howler monkeys to become what is today known as P. simium , supported by the low genetic diversity of P. simium and high similarity morphologically and genetically to P. vivax ( Escalante and Ayala, 1995 ; Lim et al, 2005 ; Mourier et al, 2021 ; de Oliveira et al, 2021 ). Since then, P. simium has built up a handful of genetic differences from P. vivax , perhaps through drift or adaptations to a new host ( Brasil et al, 2017 ; Mourier et al, 2021 ; de Oliveira et al, 2021 ).…”

“…This is consistent with a host switch of historical P. vivax into howler monkeys to become what is today known as P. simium , supported by the low genetic diversity of P. simium and high similarity morphologically and genetically to P. vivax ( Escalante and Ayala, 1995 ; Lim et al, 2005 ; Mourier et al, 2021 ; de Oliveira et al, 2021 ). Since then, P. simium has built up a handful of genetic differences from P. vivax , perhaps through drift or adaptations to a new host ( Brasil et al, 2017 ; Mourier et al, 2021 ; de Oliveira et al, 2021 ). Occasional cases of P. falciparum have also been reported in South American monkeys, though these cases are rare and largely unconfirmed ( Duarte et al, 2008 ; Yamasaki et al, 2011 ).…”

“…Genomic data provides some support for differentiation between P. simium and P. vivax ( Mourier et al, 2021 ; de Oliveira et al, 2021 ), but is weaker for P. brasilianum and P. malariae comparisons, which lack whole-genome data. Currently, most South American P. malariae cases are linked to international travel, but NHPs may serve as a reservoir for disease ( Figure 2 ).…”

“…Early genomic resources that derive from passage through monkeys are missing common RBP genes founds in human field isolates ( Hester et al, 2013 ), suggesting potential for host specificity. The first whole genomes from P. simium support a role for DBPs and RBPs in parasite evolution to new hosts or host specificity ( Mourier et al, 2021 ; de Oliveira et al, 2021 ). Without experimental studies to confirm function, caution is warranted.…”

Evolutionary history of Plasmodium vivax and Plasmodium simium in the Americas

“…The finding that only two SNPs distinguished the two species led some researchers to question the species status of P. simium [ 38 , 39 ]. The recent analysis of the first P. simium complete genomes from humans and from monkeys showed a clear genetic separation without genetic exchange (absence of genetic hybrids) between P. vivax and P. simium , a result in agreement with the existence of two distinct Plasmodium species [ 40 ].…”