Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria

Otto, Thomas D.; Gilabert, Aude; Crellen, Thomas; Böhme, Ulrike; Arnathau, Céline; Sanders, Mandy; Oyola, Samuel O.; Okouga, Alain Prince; Boundenga, Larson; Willaume, Eric; Ngoubangoye, Barthélémy; Moukodoum, Nancy Diamella; Paupy, Christophe; Durand, Patrick; Rougeron, Virginie; Ollomo, Benjamin; Renaud, François; Newbold, Chris; Berriman, Matthew; Prugnolle, Franck

doi:10.1038/s41564-018-0162-2

Cited by 133 publications

(141 citation statements)

References 79 publications

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“…2). As expected, the phylogeny was consistent with earlier reports using putatively neutral genes, genes encoding merozoite antigens, and/or mitochondrial genomes (27)(28)(29). Overall, the Laverania subgenus, which includes P. falciparum, formed a monophyletic group, as did P. vivax and its closely related nonhuman primate malaria parasites from SEA and all rodent malaria parasites.…”

Section: Resultssupporting

confidence: 89%

“…This investigation reports 10 new k13 orthologous gene sequences, obtained by nested PCR, from macaque and gibbon parasite strains and chimpanzees infected with Plasmodium reichenowi, Plasmodium billcollinsi, and Plasmodium gaboni. The sequences obtained here were aligned with those available in public databases (see Materials and Methods and Data Set S1 in the supplemental material) (27). The alignment constructed with the Plasmodium species orthologous k13 genes showed that the encoded protein is remarkably conserved across the genus.…”

Section: Resultsmentioning

confidence: 99%

“…The concordance statistic (S) showed that synonymous and nonsynonymous substitution rate changes over time were correlated (P Ͻ 0.5), suggesting that there was no pattern indicative of positive selection acting on this gene. The branch leading to P. falciparum (27,28) from the common ancestor with its closest sister taxon (Plasmodium praefalciparum) showed a synonymous substitution rate of 0.005 per codon per My, while the nonsynonymous substitution rate was 0.001 per codon per My.…”

Section: Resultsmentioning

confidence: 99%

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Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum

Pacheco

Kadakia

Chaudhary

et al. 2019

Antimicrob Agents Chemother

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Mutations in the Plasmodium falciparum k13 (Pfk13) gene are linked to delayed parasite clearance in response to artemisinin-based combination therapies (ACTs) in Southeast Asia. To explore the evolutionary rate and constraints acting on this gene, k13 orthologs from species sharing a recent common ancestor with P. falciparum and Plasmodium vivax were analyzed. These comparative studies were followed by genetic polymorphism analyses within P. falciparum using 982 complete Pfk13 sequences from public databases and new data obtained by next-generation sequencing from African and Haitian isolates. Although k13 orthologs evolve at heterogeneous rates, the gene was conserved across the genus, with only synonymous substitutions being found at residues where mutations linked to the delayed parasite clearance phenotype have been reported. This suggests that those residues were under constraint from undergoing nonsynonymous changes during evolution of the genus. No fixed nonsynonymous differences were found between Pfk13 and its orthologs in closely related species found in African apes. This indicates that all nonsynonymous substitutions currently found in Pfk13 are younger than the time of divergence between P. falciparum and its closely related species. At the population level, no mutations linked to delayed parasite clearance were found in our samples from Africa and Haiti. However, there is a high number of single Pfk13 mutations segregating in P. falciparum populations, and two predominant alleles are distributed worldwide. This pattern is discussed in terms of how changes in the efficacy of natural selection, affected by population expansion, may have allowed for the emergence of mutations tolerant to ACTs.

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Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum

Pacheco

Kadakia

Chaudhary

et al. 2019

Antimicrob Agents Chemother

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“…As the parasites of non-human primates have co-evolved with and adapted to their monkey hosts, it is impossible to predict their potential pathogenesis in zoonotic human infections. The virulence of P. falciparum , for example, has been attributed to its relatively recent emergence as a human pathogen 11 , which appears to have occurred following a single host transfer from a gorilla in Africa 5 .…”

Section: Introductionmentioning

confidence: 99%

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

Mourier

Alvarenga

Kaushik

et al. 2019

Preprint

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Oxford, Headington, Oxford, OX3 9DU, UK 41 42 §) Contributed equally, arranged alphabetically 43 †) Corresponding authors 44 45 46 Summary 47 48 Plasmodium simium, a malaria parasite of non-human primates in the Atlantic forest region of 49Brazil was recently shown to cause zoonotic infection in humans in the region. Phylogenetic 50 analyses based on the whole genome sequences of six P. simium isolates infecting humans 51 and two isolates from brown howler monkeys revealed that P. simium is monophyletic within 52 the broader diversity of South American Plasmodium vivax, consistent with the hypothesis 53 that P. simium first infected non-human primates as a result of a host-switch from humans 54 carrying P. vivax. We provide molecular evidence that the current zoonotic infections of 55 people have likely resulted from multiple independent host switches, each seeded from a 56 different monkey infection. Very low levels of genetic diversity within P. simium genomes 57 and the absence of P. simium-P. vivax hybrids suggest that the P. simium population emerged 58 recently and has subsequently experienced a period of independent evolution in Platyrrhini 59 monkeys. We further find that Plasmodium Interspersed Repeat (PIR) genes, Plasmodium 60Helical Interspersed Subtelomeric (PHIST) genes and Tryptophan-Rich Antigens (TRAg) 61 genes in P. siumium are genetically divergent from P. vivax and are enriched for non-62 synonymous single nucleotide polymorphisms, consistent with the rapid evolution of these 63 genes. Analysis of genes involved in erythrocyte invasion revealed several notable differences 64 between P. vivax and P. simium, including large deletions within the coding region of the 65 Duffy Binding Protein 1 (DBP1) and Reticulocyte Binding Protein 2a (RBP2a) genes in P. 66 simium. Genotyping of P. simium isolates from non-human primates (NHPs) and zoonotic 67 human infections showed that a precise deletion of 38 amino acids in DBP1 is exclusively 67 present in all human infecting isolates, whereas non-human primate infecting isolates were 68 polymorphic for the deletion. We speculate that these deletions in the parasite-encoded key 69 erythrocyte invasion ligands and the additional rapid genetic changes have facilitated zoonotic 70 transfer to humans. Non-human primate malaria parasites can be considered a reservoir of 71 potential infectious human parasites that must be considered in any attempt of malaria 72 elimination. The genome of P. simium will thus form an important basis for future functional 73 characterizations on the mechanisms underlying malaria zoonosis. 74 75 76 Introduction 77 78 There are currently eight species of malaria parasites known to cause disease in humans; 79 Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale 80 curtisi, Plasmodium ovale wallikeri, Plasmodium knowlesi, Plasmodium cynomolgi and 81 Plasmodium simium. The latter three species are more commonly parasitic on non-human 82 primates and have only relatively recently been shown to infect humans 1-3 . ...

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“…For instance, great apes, and even humans, can host several species of Plasmodia parasites (Prugnolle et al, 2010). EVs could mediate communication by facilitating horizontal transfer of genetic information between different Plasmodia species (Regev-Rudzki et al, 2013;Kawamura et al, 2017;Otto et al, 2018;Ben-Hur et al, 2019;Plenderleith et al, 2019). Several lines of evidence support this possibility.…”

Section: The Possible Role Of Evs In Evolution By Horizontal Gene Tramentioning

confidence: 99%

Extracellular Vesicles Could Carry an Evolutionary Footprint in Interkingdom Communication

Corrêa

Caballero

León

et al. 2020

Front. Cell. Infect. Microbiol.

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Extracellular vesicles (EVs) are minute particles secreted by the cells of living organisms. Although the functional role of EVs is not yet clear, recent work has highlighted their role in intercellular communication. Here, we expand on this view by suggesting that EVs can also mediate communication among interacting organisms such as hosts, pathogens and vectors. This inter-kingdom communication via EVs is likely to have important evolutionary consequences ranging from adaptation of parasites to specialized niches in the host, to host resistance and evolution and maintenance of parasite virulence and transmissibility. A potential system to explore these consequences is the interaction among the human host, the mosquito vector and Plasmodium parasite involved in the malaria disease. Indeed, recent studies have found that EVs derived from Plasmodium infected red blood cells in humans are likely mediating the parasite's transition from the asexual to sexual stage, which might facilitate transmission to the mosquito vector. However, more work is needed to establish the adaptive consequences of this EV signaling among different taxa. We suggest that an integrative molecular approach, including a comparative phylogenetic analysis of the molecules (e.g., proteins and nucleic acids) derived from the EVs of interacting organisms (and their closely-related species) in the malaria system will prove useful for understanding interkingdom communication. Such analyses will also shed light on the evolution and persistence of host, parasite and vector interactions, with implications for the control of vector borne infectious diseases.

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Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria

Cited by 133 publications

References 79 publications

Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum

Evolution and Genetic Diversity of the k13 Gene Associated with Artemisinin Delayed Parasite Clearance in Plasmodium falciparum

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

Extracellular Vesicles Could Carry an Evolutionary Footprint in Interkingdom Communication

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