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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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“Several pharmaceutical agents have been designed to target enzymes in the mevalonate biosynthetic pathway as therapy for multiple conditions, including hypercholesterolemia, cardiovascular disease (69), osteoporosis (16), Alzheimer disease (70), several infectious diseases (17, 18, 71), and cancer (19).”
BackgroundMok, S., Liong, K.-Y., Lim, E., Huang, X.-M., Zhu, L., Preiser, P., & Bozdech, Z. (2014) · Molecular Microbiology · doi:10.1111/mmi.12505 · Cited by 34
“putative promoters) that are also characterized by an extreme A::T content (∼80–90%) (Gardner et al., 2002).”
BackgroundInfluentialNovel inhibitors of the Plasmodium falciparum electron transport chain
Stocks, P. A., Barton, V. E., Antoine, T., Biagini, G., Ward, S., & O'Neill, P. (2014) · Parasitology · doi:10.1017/s0031182013001571 · Cited by 34
Small molecule Plasmodium FKBP35 inhibitor as a potential antimalaria agent
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Vaccination Strategies against Malaria: novel carrier(s) more than a tour de force
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Protist genomics: key to understanding eukaryotic evolution
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“Snapshot of available protist genomes One of the very fi rst protist genomes to be sequenced was that of the apicomplexan parasite Plasmodium , published in 2002 [75].”
Babesia duncani multi-omics identifies virulence factors and drug targets
Singh, P., Lonardi, S., Liang, Q., Vydyam, P., Khabirova, E., Fang, T., Gihaz, S., Thekkiniath, J., Munshi, M., Abel, S., et al. (2023) · Nature Microbiology · doi:10.1038/s41564-023-01360-8 · Cited by 38
Measurably recombining malaria parasites
Camponovo, F., Buckee, C., & Taylor, A. R. (2022) · Trends in Parasitology · doi:10.1016/j.pt.2022.11.002 · Cited by 33
“falciparum has a 23 megabase nuclear genome [14] and a SNP mutation rate on the order of 10−10 mutations per base pair per asexual generation (48 hours) [15].”
BackgroundInferring Adaptive Codon Preference to Understand Sources of Selection Shaping Codon Usage Bias
de Oliveira, J. L., Castillo-Morales, A., Hurst, L. D., Urrutia, A. O., Thompson, C. R. L., & Wolf, J. B. (2021) · Molecular Biology and Evolution · doi:10.1093/molbev/msab099 · Cited by 32
“2005), second only to the human malaria parasite Paramecium falciparum ( 19.4% GC; Gardner et al. 2002).”
BackgroundInfluentialCRISPR/Cas9‐mediated genome editing of Schistosoma mansoni acetylcholinesterase
You, H., Mayer, J. U., Johnston, R. L., Sivakumaran, H., Ranasinghe, S. L., Rivera, V., Kondrashova, O., Koufariotis, L. T., Du, X., Driguez, P., et al. (2020) · The FASEB Journal · doi:10.1096/fj.202001745rr · Cited by 38
Genome wide distribution of G-quadruplexes and their impact on gene expression in malaria parasites
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“Var upstream regions (ups) are split into different categories based on their sequence and chromosomal location [39].”
BackgroundInfluentialDisordered epitopes as peptide vaccines
MacRaild, C. A., Seow, J., Das, S. C., & Norton, R. S. (2018) · Peptide Science · doi:10.1002/pep2.24067 · Cited by 38
Plasmodium falciparum strains spontaneously switch invasion phenotype in suspension culture
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Plasmodium heme biosynthesis: To be or not to be essential?
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How genomics is contributing to the fight against artemisinin-resistant malaria parasites.
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Genome mining offers a new starting point for parasitology research
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Purine import into malaria parasites as a target for antimalarial drug development
Frame, I. J., Deniskin, R., Arora, A., & Akabas, M. H. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12568 · Cited by 42
Zenonos, Z., Rayner, J., & Wright, G. J. (2014) · Malaria Journal · doi:10.1186/1475-2875-13-93 · Cited by 33
“falciparum genome project in 2002 [10] identified the full complement of parasite proteins but progress in understanding the function of these proteins, including those displayed on the merozoite cell surface, has been hindered by the technical difficulties in expressing Plasmodium proteins in a functionally active fo…”
BackgroundJiang, J., Barnwell, J., Meyer, E., & Galinski, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063888 · Cited by 33
Choi, J.-Y., Augagneur, Y., Mamoun, C. B., & Voelker, D. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.313676 · Cited by 33
Drugs for malaria: something old, something new, something borrowed
Hobbs, C. V., & Duffy, P. E. (2011) · F1000 Biology Reports · doi:10.3410/b3-24 · Cited by 35
“The sequencing of various Plasmodium genomes [36, 37] has accelerated target identification and expression analysis.”
BackgroundThe case for PfEMP1-based vaccines to protect pregnant women againstPlasmodium falciparummalaria
Hviid, L. (2011) · Expert Review of Vaccines · doi:10.1586/erv.11.113 · Cited by 36
Antunes, P., Stürmer, S., Bever, J., Chagnon, P., Chaudhary, V., Deveautour, C., Fahey, C., Kokkoris, V., Lekberg, Y., Powell, J., et al. (2025) · Mycorrhiza · doi:10.1007/s00572-025-01187-7 · Cited by 32
“Eukaryotes with exceptionally low rDNA copy numbers often share similar characteristics, such as symbiotic and asexually reproductive lifestyles, indicating niche preference (e.g., Dalrymple 1990; Gardner et al. 2002).”
Humanized Mice and the Rebirth of Malaria Genetic Crosses
Vendrely, K. M., Kumar, S., Li, X., & Vaughan, A. (2020) · Trends in Parasitology · doi:10.1016/j.pt.2020.07.009 · Cited by 32
“falciparum (i) has a well-annotated and small (~23 Mb) reference genome [3], (ii) has a vast database of supporting functional information and associated population data [4], (iii) is haploid throughout the majority of the life cycle which simplifies phenotyping through the cloning and amplification of asexual blood s…”
BackgroundJacob, C. G., Ansbro, M. R., Amato, R., Kekre, M., Vongpromek, R., Dhorda, M., Amaratunga, C., Sreng, S., Suon, S., Miotto, O., et al. (2019) · Malaria Journal · doi:10.1186/s12936-020-03249-x · Cited by 32
Beri, D., Ramdani, G., Balan, B., Gadara, D. C., Poojary, M., Momeux, L., Tatu, U. S., & Langsley, G. (2019) · Scientific Reports · doi:10.1038/s41598-018-37816-9 · Cited by 38
McDew-White, M., Li, X., Nkhoma, S. C., Nair, S., Cheeseman, I. H., & Anderson, T. (2019) · bioRxiv · doi:10.1093/gbe/evz140 · Cited by 32
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“With a very small genome size of 6 kb and only three protein-coding genes, it is one of the smallest genomes discovered to date (6).”
BackgroundPopulation genomics of virulence genes of Plasmodium falciparum in clinical isolates from Uganda
Ruybal-Pesántez, S., Tiedje, K., Tonkin-Hill, G., Rask, T. S., Kamya, M., Greenhouse, B., Dorsey, G., Duffy, M., & Day, K. (2017) · Scientific Reports · doi:10.1038/s41598-017-11814-9 · Cited by 32
“Var genes can be further classified into four main sub-groups based on semi-conserved upstream promoter sequences (ups): groups A (upsA), B (upsB), C (upsC), and E (upsE) with group E consisting of only var2csa , a gene associated with placental malaria 9,10,17,18 .”
The GMZ2 malaria vaccine: from concept to efficacy in humans
Theisen, M., Adu, B., Mordmüller, B. G., & Singh, S. C. (2017) · Expert Review of Vaccines · doi:10.1080/14760584.2017.1355246 · Cited by 38
Hill, R. J., Ringel, A. R., Knuepfer, E., Moon, R., Blackman, M., & van Ooij, C. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.740506 · Cited by 32
“Most members of the genus Plasmodium, which are the obligate intracellular parasites that cause malaria, encode four START proteins (19).”
BackgroundEpitope Identification from Fixed-complexity Random-sequence Peptide Microarrays
Richer, J., Johnston, S. A., & Stafford, P. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.043513 · Cited by 32
Warimwe, G. M., Recker, M., Kiragu, E. W., Buckee, C. O., Wambua, J., Musyoki, J., Marsh, K., & Bull, P. C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0070467 · Cited by 50
“PfEMP1 are encoded by about 60 var genes per parasite genome and expressed on the infected erythrocyte (IE) surface where they mediate cytoadhesion of IE to host receptors such as ICAM1 and CD36 [5,6].”
BackgroundAlexandre, J. S. F., Yahata, K., Kawai, S., Torii, M., & Kaneko, O. (2011) · Parasitology international · doi:10.1016/j.parint.2011.05.003 · Cited by 32
Schneider, V. M., Visone, J. E., Harris, C. T., Florini, F., Hadjimichael, E., Zhang, X., Gross, M., Rhee, K. Y., Mamoun, C. B., Kafsack, B. F. C., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2302152120 · Cited by 36
The C- and G-value paradox with polyploidy, repeatomes, introns, phenomes and cell economy
Choi, I., Kwon, E., & Kim, N. (2020) · Genes & Genomics · doi:10.1007/s13258-020-00941-9 · Cited by 46
The role of epigenetics and chromatin structure in transcriptional regulation in malaria parasites.
Abel, S., & Roch, K. L. L. (2019) · Briefings in Functional Genomics · doi:10.1093/bfgp/elz005 · Cited by 31
“Its genome is composed of 23 million base pairs per haploid genome, arranged into 14 chromosomes [3].”
BackgroundPandey, R. K., Ali, M., Ojha, R., Bhatt, T. K., & Prajapati, V. K. (2018) · Vaccine · doi:10.1016/j.vaccine.2018.05.082 · Cited by 38
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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