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Abstract

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

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Most cited references 34

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A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses.

Neil Hall, Marianna Karras, J. Dale Raine … (2005)

Plasmodium berghei and Plasmodium chabaudi are widely used model malaria species. Comparison of their genomes, integrated with proteomic and microarray data, with the genomes of Plasmodium falciparum and Plasmodium yoelii revealed a conserved core of 4500 Plasmodium genes in the central regions of the 14 chromosomes and highlighted genes evolving rapidly because of stage-specific selective pressures. Four strategies for gene expression are apparent during the parasites' life cycle: (i) housekeeping; (ii) host-related; (iii) strategy-specific related to invasion, asexual replication, and sexual development; and (iv) stage-specific. We observed posttranscriptional gene silencing through translational repression of messenger RNA during sexual development, and a 47-base 3' untranslated region motif is implicated in this process.

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Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii.

Jane M-R Carlton, Samuel V. Angiuoli, Bernard B Suh … (2002)

Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease.

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Relapses of Plasmodium vivax infection usually result from activation of heterologous hypnozoites.

Mallika Imwong, Georges Snounou, Sasithon Pukrittayakamee … (2007)

Relapses originating from hypnozoites are characteristic of Plasmodium vivax infections. Thus, reappearance of parasitemia after treatment can result from relapse, recrudescence, or reinfection. It has been assumed that parasites causing relapse would be a subset of the parasites that caused the primary infection. Paired samples were collected before initiation of antimalarial treatment and at recurrence of parasitemia from 149 patients with vivax malaria in Thailand (n=36), where reinfection could be excluded, and during field studies in Myanmar (n=75) and India (n=38). Combined genetic data from 2 genotyping approaches showed that novel P. vivax populations were present in the majority of patients with recurrent infection (107 [72%] of 149 patients overall [78% of patients in Thailand, 75% of patients in Myanmar {Burma}, and 63% of patients in India]). In 61% of the Thai and Burmese patients and in 55% of the Indian patients, the recurrent infections contained none of the parasite genotypes that caused the acute infection. The P. vivax populations emerging from hypnozoites commonly differ from the populations that caused the acute episode. Activation of heterologous hypnozoite populations is the most common cause of first relapse in patients with vivax malaria.

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Author and article information

Journal

PubMed ID:: 18843361

PMC ID:: 2651158

DOI:: 10.1038/nature07327

ScienceOpen disciplines: Chemistry

Keywords: Amino Acid Motifs,Animals,Artemisinins,metabolism,pharmacology,Atovaquone,Cell Nucleus,genetics,Chromosomes,Conserved Sequence,Erythrocytes,parasitology,Evolution, Molecular,Genome, Protozoan,Genomics,Haplorhini,Humans,Isochores,Ligands,Malaria, Vivax,Multigene Family,Plasmodium vivax,drug effects,pathogenicity,physiology,Sequence Analysis, DNA,Species Specificity,Synteny

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ScienceOpen disciplines: Chemistry

Comments

Camila França wrote:

Malaria vaccine development collection topic 5) Identifying and developing the new generation of malaria vaccines - Making use of reverse vaccinology and serology information:

See https://www.scienceopen.com/collection/malariavaccine

The availability of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this parasite. Here the structure and regions of synteny are described for P. vivax chromosomes. Carlton and colleagues show how this parasite resembles other malaria parasites in gene content and metabolic potential, and describe novel gene families and potential alternative invasion pathways.

2018-10-08 18:14 UTC

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