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Genome sequence of the human malaria parasite Plasmodium falciparum
Open accessAbstract
The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria.
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“we calculated that 1 μg of P. falciparum DNA is equal to 4.067 × 107 genome copies or one genome copy in 24.6 fg of DNA.”
From Real-Time PCR for Detection and Identification of Plasmodium spp (2005) · cites this paper as [11]
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“The 18S rRNA gene was chosen as the target since it contains both highly conserved and variable regions, and at least five copies of the gene are dispersed on separate chromosomes of the Plasmodium genome (11, 20).”
From Real-Time PCR for Detection and Identification of Plasmodium spp (2005) · cites this paper as [11]
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“By targeting a gene with multiple copies dispersed throughout the Plasmodium genome (11), the sensitivity of this assay is greater than if a single-copy gene was chosen.”
From Real-Time PCR for Detection and Identification of Plasmodium spp (2005) · cites this paper as [11]
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Self-citationThe mRNA-bound proteome of the human malaria parasite Plasmodium falciparum
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“falciparum genome over a decade ago [4], much effort has been put into deciphering patterns of gene expression in the parasite, motivated by the notion that this will increase our understanding of parasite biology and reveal attractive targets for novel antimalarial drugs [5–7].”
BackgroundAntibodies against Plasmodium falciparum malaria at the molecular level
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Parasite Sensing of Host Nutrients and Environmental Cues
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Structural and evolutionary divergence of eukaryotic protein kinases in Apicomplexa
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“Recent whole-genome sequencing efforts have targeted a number of apicomplexan species [6-17].”
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“3 Mb in size and encodes over 5,400 genes (3).”
BackgroundSelf-citationRevisiting gametocyte biology in malaria parasites
Ngotho, P., Soares, A. B., Hentzschel, F., Achcar, F., Bertuccini, L., & Marti, M. (2019) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuz010 · Cited by 110
Malaria Parasites: The Great Escape
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“falciparum parasites possess ~60 var genes distributed over the 14 chromosomes of the parasite (37).”
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“It has previously been reported that the parasite does not possess any of the remaining genes in the branched-chain amino acid degradation pathway (2, 38, 46, 47), leaving the function of the enzyme complex an open question.”
BackgroundAdvances in microfluidics in combating infectious diseases
Tay, A. K. P., Pavesi, A., Yazdi, S. R., Lim, C. T., & Warkiani, M. E. (2016) · Biotechnology Advances · doi:10.1016/j.biotechadv.2016.02.002 · Cited by 103
“Malaria infection by Plasmodium protozoa through the intermediate host, Anopheles mosquito is currently most common (Gardner et al., 2002).”
A Network Approach to Analyzing Highly Recombinant Malaria Parasite Genes
Larremore, D. B., Clauset, A. J., & Buckee, C. O. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003268 · Cited by 107
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“Complete P. falciparum genome sequence analysis localized var gene members either to highly polymorphic chromosome ends or to central chromosome regions (Gardner et al., 2002).”
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Population genomic structure and adaptation in the zoonotic malaria parasite Plasmodium knowlesi
Assefa, S., Lim, C., Preston, M. D., Duffy, C. W., Nair, M. B., Adroub, S. A., Kadir, K. A., Goldberg, J. M., Neafsey, D. E., Divis, P. C. S., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1509534112 · Cited by 79
“knowlesi reference genome sequence (strain H) highlighted some unique features of the genome of this species (19), namely, schizont infected cell agglutination variant (SICAvar) and knowlesi interspersed repeat (KIR) variant antigen genes, which were widely dispersed instead of being predominantly localized in subtelo…”
BackgroundSelf-citationCo-transmission of Related Malaria Parasite Lineages Shapes Within-Host Parasite Diversity
Nkhoma, S. C., Trevino, S. G., Gorena, K. M., Nair, S., Khoswe, S., Jett, C., Garcia, R., Daniel, B. J., Dia, A., Terlouw, D. J., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.12.001 · Cited by 114
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Self-citationThe role of PfEMP1 adhesion domain classification in Plasmodium falciparum pathogenesis research
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Evolutionary analysis of the most polymorphic gene family in falciparum malaria
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“(2) A small proportion of sequence sharing that appears to originate from drug induced selective sweeps;”
BackgroundMethodSelf-citationThe genomic architecture of antimalarial drug resistance
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“falciparum genome is highly AT-rich and has common AT monomeric tracts [118], CNVs are an important mechanism of evolutionary adaptation [117, 119, 120].”
BackgroundGenome-wide Mapping of DNA Methylation in the Human Malaria Parasite Plasmodium falciparum
Ponts, N., Fu, L., Harris, E. Y., Zhang, J., Chung, D.-W. D., Cervantes, M. C., Prudhomme, J. G., Atanasova‐Pénichon, V., Zehraoui, E., Bunnik, E. M., et al. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.11.007 · Cited by 107
“falciparum consists of 14 chromosomes, encodes about 5,500 genes, and is the most AT-rich genome sequenced to date (more than 90% in intergenic regions; Gardner et al., 2002).”
BackgroundTonkin‐Hill, G. Q., Trianty, L., Noviyanti, R., Nguyen, H. H. T., Sebayang, B. F., Lampah, D. A., Marfurt, J., Cobbold, S. A., Rambhatla, J. S., McConville, M. J., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2004328 · Cited by 127
“Even with such large sequence diversity, var genes can be classified into three broad groups based on their upstream sequence (UPS; A, B, and C) [12,17].”
A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites
Guggisberg, A. M., Park, J., Edwards, R. L., Ken, M. L., Hodge, D. M., Tolia, N., & Odom, A. R. (2014) · Nature Communications · doi:10.1038/ncomms5467 · Cited by 89
“The P. falciparum strain used for FSM selection is derived from genome reference strain 3D7 45 .”
Single-cell genomics for dissection of complex malaria infectionsPreprint
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“The 3D7 (Gardner et al. 2002), Dd2, and Hb3 (Volkman et al. 2007) P. falciparum parasite lines are well-characterized, fully sequenced isolates that are readily grown in the laboratory.”
BackgroundInfluentialThe triumph of good over evil: protection by the sickle gene against malaria
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A plausible mechanism for the antimalarial activity of artemisinin: A computational approach
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“, 1998), with no type I FAS genes found in these organisms (Gardner et al., 2002).”
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“falciparum genome size is 23 mega bases [18] and on the assumption that the average weight of one mole of a base pair is 650 g, 1 ng of parasite genomic DNA corresponds to 40,000 copies of the target gene.”
BackgroundDeconvoluting heme biosynthesis to target blood-stage malaria parasites
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BackgroundPfAlbas constitute a new eukaryotic DNA/RNA-binding protein family in malaria parasites
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ATP Synthase Complex of Plasmodium falciparum
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“falciparum genome (15), transcriptome (4), and proteome (13) data as a starting point and screened the proteins in this data set based on four features: (i) late-schizont stage transcription, (ii) smaller gene size ( 2.”
BackgroundMethodMalaria life cycle intensifies both natural selection and random genetic drift
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Host Reticulocytes Provide Metabolic Reservoirs That Can Be Exploited by Malaria Parasites
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“We identified the following genes located in such ‘valleys’ of low diversity (number of SNP hits) in the genome-wide scan: (i) PFA0205w (2), (ii) PFA0220w (UBP1-homologue) (1), (iii) PFC0935c (2) (coding for a putative N-acetylglucosamine-1-phosphate transferase), (iv) PFC0940c (1), (v) PFE1210c (1), (vi) PFF1350c (13…”
Metadata
- Authors
- Gardner, M. J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R. W., Carlton, J. M., Pain, A., Nelson, K. E., Bowman, S., Paulsen, I. T., James, K., Eisen, J. A., Rutherford, K., Salzberg, S. L., Craig, A., Kyes, S., Chan, M.-S., Nene, V., Shallom, S. J., Suh, B., Peterson, J., Angiuoli, S., Pertea, M., Allen, J., Selengut, J., Haft, D., Mather, M. W., Vaidya, A. B., Martin, D. M. A., Fairlamb, A. H., Fraunholz, M. J., Roos, D. S., Ralph, S. A., McFadden, G. I., Cummings, L. M., Subramanian, G. M., Mungall, C., Venter, J. C., Carucci, D. J., Hoffman, S. L., Newbold, C., Davis, R. W., Fraser, C. M., & Barrell, B.
- Affiliations
- J. Craig Venter Institute (US)
- Corresponding author
- Gardner, Malcolm J.
- ORCID
- Gardner, Malcolm J.
- Hall, Neil
- Fung, Eula
- White, Owen
- Berriman, Matthew
- Hyman, Richard W.
- Carlton, Jane M.
- Pain, Arnab
- Paulsen, Ian T.
- Eisen, Jonathan A.
- Rutherford, Kim
- Salzberg, Steven L.
- Craig, Alister
- Nene, Vishvanath
- Pertea, Mihaela
- Allen, Jonathan
- Haft, Daniel
- Mather, Michael W.
- Vaidya, Akhil B.
- Martin, David M. A.
- Fairlamb, Alan H.
- Fraunholz, Martin J.
- Roos, David S.
- Ralph, Stuart A.
- McFadden, Geoffrey I.
- Mungall, Chris
- Venter, J. Craig
- Hoffman, Stephen L.
- Newbold, Chris
- Davis, Ronald W.
- Fraser, Claire M.
- Venue
- Nature
- Published
- 2002-10
- Volume
- 419
- Issue
- 6906
- Pages
- 498-511
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3836256
- OpenAlex
- W2019851585
- Cited by
- 4,407
- References
- 170
- Citations by year
- 2026: 68 · 2025: 107 · 2024: 112 · 2023: 107 · 2022: 154 · 2021: 151 · 2020: 148 · 2019: 140 · 2018: 150 · 2017: 160 · 2016: 183 · 2015: 166 · 2014: 213 · 2013: 191 · 2012: 211
- FWCI
- 272.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- Funders
- Burroughs Wellcome Fund
- Global Fund to Fight AIDS, Tuberculosis and Malaria
- Wellcome Trust (061524)
- Stanford Bio-X
- National Institute of Allergy and Infectious Diseases (R01AI028398)
- Medical Research and Materiel Command
- Naval Medical Research Center
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- Plasmodium falciparum, Plasmodium, genome sequence, nuclear genome, antigenic variation, subtelomeric regions, immune evasion, host-parasite interactions, apicoplast, isoprenoid metabolism, gene content, drug and vaccine targets
- MeSH terms
- Animals, DNA Repair, DNA Replication, Humans, Molecular Sequence Data, Plasmodium falciparum, Recombination, Genetic, Protozoan Proteins, DNA, Protozoan, Malaria, Falciparum, Sequence Analysis, DNA, Malaria Vaccines, Plastids, Genome, Protozoan, Evolution, Molecular, Proteome, Chromosome Structures, Membrane Transport Proteins
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