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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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“falciparum genome, which has about 23 million bases of DNA organized into 14 chromosomes and about 5,000 genes (8).”
BackgroundBelmonte‐Reche, E., Martínez‐García, M., Guédin, A., Zuffo, M., Arévalo‐Ruiz, M., Doria, F., Campos‐Salinas, J., Maynadier, M., Lopez-Rubio, J.-J., Freccero, M., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01672 · Cited by 77
der Wel, A. M. V.-V., Roma, G., Gupta, D., Schuierer, S., Nigsch, F., Carbone, W., Zeeman, A., Lee, B.-O. H., Hofman, S., Faber, B., et al. (2017) · eLife · doi:10.7554/elife.29605 · Cited by 65
“…genes are highly expressed in hypnozoites, and while canonical non-homologous end joining (NHEJ) DNA- repair pathways are not present in Plasmodium (Gardner et al., 2002), we detected most of the homologous recombination repair (HR) enzymes as well as genes required for the maintenance…”
BackgroundMarwaha, A., White, J. C., Mazouni, F. E., Creason, S. A., Kokkonda, S., C, F. S. B. A., Charman, S. A., Phillips, M. A., & Rathod, P. K. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm300351w · Cited by 68
The role of collectivism in modeling the adoption of renewable energies: a cross-cultural approach
Higueras‐Castillo, E., Liébana-Cabanillas, F. J., Muñoz‐Leiva, F., & Molinillo, S. (2019) · International Journal of Environmental Science and Technology · doi:10.1007/s13762-019-02235-4 · Cited by 73
Lu, F., Li, J., Wang, B., Cheng, Y., Kong, D.-H., Cui, L., Ha, K., Sattabongkot, J., Tsuboi, T., & Han, E. (2014) · Journal of Proteomics · doi:10.1016/j.jprot.2014.02.029 · Cited by 59
Lysine Acetylation in Sexual Stage Malaria Parasites Is a Target for Antimalarial Small Molecules
Trenholme, K. R., Marek, L., Duffy, S., Pradel, G., Fisher, G. M., Hansen, F. K., Skinner‐Adams, T. S., Butterworth, A., Ngwa, C. J., Moecking, J., et al. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02721-13 · Cited by 72
Self-citationChang, H., Park, D. J., Galinsky, K. J., Schaffner, S. F., Ndiaye, D., Ndir, O., Mboup, S., Wiegand, R. C., Volkman, S. K., Sabeti, P. C., et al. (2012) · Molecular Biology and Evolution · doi:10.1093/molbev/mss161 · Cited by 64
“falciparum genome (81%; Gardner et al. 2002) is maintained as a dynamic equilibrium between mutation and selection pressures operating on nucleotide composition.”
BackgroundAre Eimeria Genetically Diverse, and Does It Matter?
Clark, E., Tomley, F., & Blake, D. (2017) · Trends in Parasitology · doi:10.1016/j.pt.2016.08.007 · Cited by 63
“The seven Eimeria species which infect poultry do not appear to possess 206 the sub-telomeric regions which in P. falciparum contain a set of plastic genes involved 207 in host immune system evasion (Gardner et al., 2002, Ling et al., 2007, Reid et al., 208 2014).”
BackgroundHasan, M. A., Mazumder, M. H. H., Chowdhury, A. S., Datta, A., & Khan, M. A. (2015) · Source Code for Biology and Medicine · doi:10.1186/s13029-015-0037-3 · Cited by 63
“falciparum infected erythrocytes [13, 14].”
Teguh, S. C., Klonis, N., Duffy, S., Lucantoni, L., Avery, V., Hutton, C., Baell, J., & Tilley, L. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400656s · Cited by 63
Parasite-Produced MIF Cytokine: Role in Immune Evasion, Invasion, and Pathogenesis
Ghosh, S., Jiang, N., Farr, L., Ngobeni, R., & Moonah, S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01995 · Cited by 62
“For example, Plasmodium falciparum, a protozoan parasite responsible for most human malaria, accounted for an estimated 200millionmalaria cases and roughly 500,000malaria deaths in 2015 (1, 2).”
BackgroundNanopore sequencing of drug-resistance-associated genes in malaria parasites, Plasmodium falciparum
Runtuwene, L., Tuda, J., Mongan, A., Makałowski, W., Frith, M., Imwong, M., Srisutham, S., Thi, L. A. N., Tuan, N. N., Eshita, Y., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-26334-3 · Cited by 62
Favuzza, P., Guffart, E., Tamborrini, M., Scherer, B., Dreyer, A. M., Rufer, A. C., Erny, J., Hoernschemeyer, J., Thoma, R., Schmid, G., et al. (2017) · eLife · doi:10.7554/elife.20383 · Cited by 69
Yang, Y., Xiong, J., Zhou, Z., Huo, F., Miao, W., Ran, C., Liu, Y., Zhang, J., Feng, J.-M., Wang, M., et al. (2014) · Genome Biology and Evolution · doi:10.1093/gbe/evu247 · Cited by 86
Nyasembe, V. O., Tchouassi, D. P., Kirwa, H. K., Foster, W. A., Teal, P. E. A., Borgemeister, C., & Torto, B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0089818 · Cited by 58
“However, the development of an effective vaccine has been hampered by the complexity of the parasite and its life cycle [7,8], extensive antigenic variation [9], and a poor understanding of the interaction between Plasmodium falciparum and the human immune system [10].”
BackgroundThe Multiple Levels of Mitonuclear Coregulation
Isaac, R. S., McShane, E., & Churchman, L. S. (2018) · Annual Review of Genetics · doi:10.1146/annurev-genet-120417-031709 · Cited by 63
“Consequently, mitochondrial genomes vary greatly in size and gene content, ranging from 3 protein-coding genes in the apicomplexan Plasmodium falciparum to 67 in the flagellate Reclinomonas americana (51, 142).”
Ke, H., Dass, S., Morrisey, J. M., Mather, M. W., & Vaidya, A. B. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002552 · Cited by 59
“The nuclear genome is composed of 14 chromosomes (23 mega base pairs) and encodes 5500 proteins (2).”
BackgroundSelf-citationHost cell remodeling by pathogens: the exomembrane system in Plasmodium-infected erythrocytes
Sherling, E. S., & van Ooij, C. (2016) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuw016 · Cited by 61
“Plasmodium spp. encode five PLPs (Carlton et al. 2002; Gardner et al. 2002), of which two are expressed during the blood stages (Kaiser et al. 2004; Garg et al. 2013).”
BackgroundLarge screen approaches to identify novel malaria vaccine candidates
Davies, D. H., Duffy, P. E., Bodmer, J.-L., Felgner, P. L., & Doolan, D. L. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.09.059 · Cited by 53
Bachmann, A., Scholz, J., Janßen, M., Klinkert, M., Tannich, E., Bruchhaus, I., & Petter, M. (2015) · Malaria Journal · doi:10.1186/s12936-015-0784-2 · Cited by 61
Stevenson, L., Huda, P., Jeppesen, A., Laursen, E., Rowe, J. A., Craig, A. G., Streicher, W. W., Barfod, L. K., & Hviid, L. (2014) · Cellular Microbiology · doi:10.1111/cmi.12403 · Cited by 58
Self-citationSierra-Miranda, M., Delgadillo, D. M., Mancio-Silva, L., Vargas, M., Villegas-Sepúlveda, N., Martínez-Calvillo, S., Scherf, A., & Hernández-Rivas, R. (2012) · Molecular and biochemical parasitology (Print) · doi:10.1016/j.molbiopara.2012.06.005 · Cited by 61
“falciparum, TARE-6 is the largest repetitive element (6 to 23 kb) of the subtelomeric region [7,8,41].”
BackgroundThe Structural, Functional and Evolutionary Impact of Transposable Elements in Eukaryotes
Almojil, D., Bourgeois, Y., Falis, M., Hariyani, I. E., Wilcox, J. J. S., & Boissinot, S. (2021) · Genes · doi:10.3390/genes12060918 · Cited by 80
“9 Mbp genome of Encephalitozoon intestinalis and the 23 Mbp genome of the malaria parasite Plasmodium falciparum are completely devoid of TEs [43,44].”
BackgroundThe transportome of the malaria parasite
Martin, R. E. (2019) · Biological Reviews of The Cambridge Philosophical Society · doi:10.1111/brv.12565 · Cited by 60
Fitness Costs and the Rapid Spread of kelch13-C580Y Substitutions Conferring Artemisinin Resistance
Nair, S., Li, X., Arya, G.-A., McDew-White, M., Ferrari, M., Nosten, F., & Anderson, T. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00605-18 · Cited by 60
Janitzek, C. M., Matondo, S., Thrane, S., Nielsen, M. A., Kavishe, R. A., Mwakalinga, S., Theander, T. G., Salanti, A., & Sander, A. F. (2016) · Malaria Journal · doi:10.1186/s12936-016-1574-1 · Cited by 64
Identification of pathogen genomic variants through an integrated pipeline
Manary, M. J., Singhakul, S. S., Flannery, E., Bopp, S., Corey, V., Bright, A., McNamara, C., Walker, J., & Winzeler, E. (2014) · BMC Bioinformatics · doi:10.1186/1471-2105-15-63 · Cited by 60
“5 Mb genome of Plasmodium falciparum, the apicomplexan parasite and etiological agent of human malaria, which has also served as a model for eukaryotic pathogen genomics since the completion and full assembly of its genome sequence in 2002 [2].”
BackgroundUddin, T., McFadden, G. I., & Goodman, C. D. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01161-17 · Cited by 73
Self-citationPlasmodium vivax vaccine research - we've only just begun.
Tham, W., Beeson, J. G., & Rayner, J. (2017) · International Journal of Parasitology · doi:10.1016/j.ijpara.2016.09.006 · Cited by 59
“Identifying the best vaccine antigens has fixated the field ever since, especially since the true scale of potential targets was revealed with the publication of the first P. falciparum genome in 2002 (Gardner et al., 2002), followed in 2008 by the P. vivax genome (Carlton et al., 2008).”
BackgroundWeaver, R., Reiling, L., Feng, G., Drew, D. R., Müeller, I., Siba, P. M., Tsuboi, T., Richards, J. S., Fowkes, F. J. I., & Beeson, J. G. (2016) · Scientific Reports · doi:10.1038/srep33094 · Cited by 64
Transport proteins of parasitic protists and their role in nutrient salvage
Dean, P., Major, P. F., Nakjang, S., Hirt, R. P., & Embley, T. M. (2014) · Frontiers in Plant Science · doi:10.3389/fpls.2014.00153 · Cited by 56
“REVIEW ARTICLE published: 29 April 2014 doi: 10.3389/fpls.2014.00153 Transport proteins of parasitic protists and their role in nutrient salvage”
BackgroundInfluentialBueno, J. M., Herreros, E., Angulo-Barturen, I., Ferrer, S., Fiandor, J., Gamo, F., Gargallo-Viola, D., & Derimanov, G. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.177 · Cited by 59
Novel Strategies for Malaria Vaccine Design
Frimpong, A., Kusi, K. A., Ofori, M. F., & Ndifon, W. O. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02769 · Cited by 70
“falciparum has been available since 2002 (70).”
BackgroundMultiple essential functions of Plasmodium falciparum actin-1 during malaria blood-stage development
Das, S., Lemgruber, L., Tay, C. L., Baum, J., & Meissner, M. (2017) · BMC Biology · doi:10.1186/s12915-017-0406-2 · Cited by 58
“falciparum genome encodes two actin genes [34], actin-1 (pfact1) and actin-2 (pfact2), with PfACT1 expressed ubiquitously throughout all life-cycle stages, and PfACT2 confined to the mosquito stages and transmittable sexual stages [35].”
Saraf, A., Cervantes, S., Bunnik, E., Ponts, N., Sardiu, M., Chung, D. D., Prudhomme, J., Varberg, J., Wen, Z.-H., Washburn, M., et al. (2016) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00366 · Cited by 58
Supporting malaria elimination with 21st century antimalarial agent drug discovery
Diagana, T. T. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.06.009 · Cited by 59
Landscape and dynamics of transcription initiation in the malaria parasite Plasmodium falciparum
Adjalley, S., Chabbert, C., Klaus, B., Pelechano, V., & Steinmetz, L. (2015) · bioRxiv · doi:10.1101/024356 · Cited by 58
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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