Characterizing the genetic diversity of the monkey malaria parasite Plasmodium cynomolgi

Sutton, Patrick L.; Luo, Zunping; Divis, Paul Cliff Simon; Friedrich, Volney K; Conway, David J.; Singh, Balbir; Barnwell, John W.; Carlton, Jane M.; Sullivan, Steven A.

doi:10.1016/j.meegid.2016.03.009

Cited by 25 publications

(24 citation statements)

References 61 publications

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“…This was further confirmed by a recent study that analysed the diversity of several P . cynomolgi isolates 45 . Although the authors proposed to call the isolate M/B, we will use the M(ulligan) nomenclature for continuity.…”

Section: Resultsmentioning

confidence: 99%

An improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion

Pasini¹,

Böhme²,

Rutledge³

et al. 2017

Wellcome Open Res

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Background: Plasmodium cynomolgi, a non-human primate malaria parasite species, has been an important model parasite since its discovery in 1907. Similarities in the biology of P. cynomolgi to the closely related, but less tractable, human malaria parasite P. vivax make it the model parasite of choice for liver biology and vaccine studies pertinent to P. vivax malaria. Molecular and genome-scale studies of P. cynomolgi have relied on the current reference genome sequence, which remains highly fragmented with 1,649 unassigned scaffolds and little representation of the subtelomeres. Methods: Using long-read sequence data (Pacific Biosciences SMRT technology), we assembled and annotated a new reference genome sequence, PcyM, sourced from an Indian rhesus monkey. We compare the newly assembled genome sequence with those of several other Plasmodium species, including a re-annotated P. coatneyi assembly. Results: The new PcyM genome assembly is of significantly higher quality than the existing reference, comprising only 56 pieces, no gaps and an improved average gene length. Detailed manual curation has ensured a comprehensive annotation of the genome with 6,632 genes, nearly 1,000 more than previously attributed to P. cynomolgi. The new assembly also has an improved representation of the subtelomeric regions, which account for nearly 40% of the sequence. Within the subtelomeres, we identified more than 1300 Plasmodium interspersed repeat ( pir) genes, as well as a striking expansion of 36 methyltransferase pseudogenes that originated from a single copy on chromosome 9. Conclusions: The manually curated PcyM reference genome sequence is an important new resource for the malaria research community. The high quality and contiguity of the data have enabled the discovery of a novel expansion of methyltransferase in the subtelomeres, and illustrates the new comparative genomics capabilities that are being unlocked by complete reference genomes.

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Section: Resultsmentioning

confidence: 99%

An improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion

Pasini¹,

Böhme²,

Rutledge³

et al. 2017

Wellcome Open Res

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“…Experimental design. A case of severe and complicated malaria in an animal from a cohort of five Macaca mulatta (Indian rhesus macaques) experimentally infected with P. cynomolgi M/B strain 22 is presented here. A detailed description of the experimental procedures, animal housing, enrichment activities, clinical interventions, hematological parameters, and clinical outcomes has been reported previously.…”

Section: Methodsmentioning

confidence: 99%

Case Report: Severe and Complicated Cynomolgi Malaria in a Rhesus Macaque Resulted in Similar Histopathological Changes as Those Seen in Human Malaria

Joyner

Wood

Moreno

et al. 2017

The American Journal of Tropical Medicine and Hygiene

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Histopathological data collected from patients with severe malaria have been instrumental for studying malaria pathogenesis. Animal models of malaria are critical to complement such studies. Here, the histopathological changes observed in a rhesus macaque with severe and complicated malaria are reported. The animal presented with thrombocytopenia, severe anemia, and hyperparasitemia during the acute infection. The macaque was given subcurative antimalarial treatment, fluid support, and a blood transfusion to treat the clinical complications, but at the time of transfusion, kidney function was compromised. These interventions did not restore kidney function, and the animal was euthanized due to irreversible renal failure. Gross pathological and histological examinations revealed that the lungs, kidneys, liver, spleen, and bone marrow exhibited abnormalities similar to those described in patients with malaria. Overall, this case report illustrates the similarities in the pathophysiological complications that can occur in human malaria and cynomolgi malaria in rhesus macaques.

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“…where p is the frequency of the i th allele and n is the number of alleles sampled [26]. LIAN version 3.7 was used for analyzing overall multilocus linkage disequilibrium (LD) implementing a standardized index of association ( ).…”

Section: Measures Of Diversitymentioning

confidence: 99%

Polymorphic markers for identification of parasite population in Plasmodium malariae

Mathema

Nakeesathit

Pagornrat

et al. 2020

Preprint

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Background Molecular genotyping in Plasmodium serves many aims including providing tools for studying parasite population genetics and distinguishing recrudescence from reinfection. Microsatellite typing, insertion-deletion (INDEL) and single nucleotide polymorphisms is used for genotyping, but only limited information is available for Plasmodium malariae, an important human malaria species. This study aimed to provide a set of genetic markers to facilitate the study of P. malariae population genetics. Methods Markers for microsatellite genotyping and pmmsp1 gene polymorphisms were developed and validated in symptomatic P. malariae field isolates from Myanmar (N=37). Fragment analysis was used to determine allele sizes at each locus to calculate multiplicity of infections (MOI), linkage disequilibrium, genetic richness index, heterozygosity and construct dendrograms. Nucleotide diversity (π), number of haplotypes, and genetic diversity (Hd) were assessed and a phylogenetic tree was constructed. Genome-wide microsatellite maps with annotated regions of newly identified markers were constructed. Results Six microsatellite markers were developed and tested in 37 P. malariae isolates which showed sufficient heterozygosity (0.530-0.922), genetic richness index (0.050-0.250) and absence of linkage disequilibrium (IAS = 0.03, p-value > 0.05)(N=37). In addition, a tandem repeat (VNTR)-based pmmsp1 INDEL polymorphisms marker was developed and assessed in 27 P. malariae isolates showing a nucleotide diversity of 0.0976, haplotype gene diversity of 0.698 and identified 14 unique variants. The size of VNTR consensus repeat unit adopted as allele was 27 base pairs. The markers Pm12_426 andpmmsp1 showed greatest diversity with heterozygosity scores of 0.920 and 0.835, respectively. Using six microsatellites markers, the likelihood that any two parasite strains would have the same microsatellite genotypes was 8.46 × 10-4 and was further reduced to 1.66 × 10-4 when pmmsp1 polymorphisms were included. Conclusions Six novel microsatellites genotyping markers and a set of pmmsp1 VNTR-based INDEL polymorphisms markers for P. malariae were developed and validated. Each marker could be independently or in combination employed to access genotyping of the parasite. The newly developed markers may serve as a useful tool for investigating parasite diversity, population genetics, molecular epidemiology and for distinguishing recrudescence from reinfection in drug efficacy studies.

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Characterizing the genetic diversity of the monkey malaria parasite Plasmodium cynomolgi

Cited by 25 publications

References 61 publications

An improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion

An improved Plasmodium cynomolgi genome assembly reveals an unexpected methyltransferase gene expansion

Case Report: Severe and Complicated Cynomolgi Malaria in a Rhesus Macaque Resulted in Similar Histopathological Changes as Those Seen in Human Malaria

Polymorphic markers for identification of parasite population in Plasmodium malariae

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