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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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BackgroundTargeting the Redox Metabolism ofPlasmodium Falciparum
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“A breakthrough was observed when the whole genome sequence of the 3D7 strain of P. falciparum was completed by Gardner et al. (2002), thus providing new opportunities in malaria studies as whole-genome gene expression profiling methods can now be utilized [131].”
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Producing parasitic helminth reference and draft genomes at the Wellcome Trust Sanger Institute
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“falciparum has been sequenced and partial genes have been annotated functionally, which may reveal some underlying mechanisms for physiological activities of malaria parasites (Gardner et al., 2002).”
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MethodSelf-citationHigh-level expression of Falcipain-2 in Escherichia coli by codon optimization and auto-induction
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“The data in the present study are in some degree consistent with the reports of K1 being the most prevalent type in the Thailand [10], Thailand– Myanmar border [53], and Thailand–Cambodia border [53], but is contrast to previous reports from in Thailand–Laos border [53] and Peru [54], with the 3D7 being the most preva…”
ResultAligner optimization increases accuracy and decreases compute times in multi-species sequence data
Robinson, K. M., Hawkins, A. S., Santana-Cruz, I., Adkins, R. S., Shetty, A. C., Nagaraj, S., Sadzewicz, L., Tallon, L. J., Rasko, D. A., Fraser, C. M., et al. (2017) · Microbial Genomics · doi:10.1099/mgen.0.000122 · Cited by 33
Self-citationTranslation in Organelles of Apicomplexan Parasites.
Habib, S., Vaishya, S., & Gupta, K. (2016) · Trends in Parasitology · doi:10.1016/j.pt.2016.07.005 · Cited by 27
Fraschka, S. A. K., Henderson, R., & Bártfai, R. (2016) · Scientific Reports · doi:10.1038/srep31965 · Cited by 30
“Z 46–49 .”
Dinko, B., & Pradel, G. (2016) · Advances in Infectious Diseases · doi:10.4236/aid.2016.62011 · Cited by 23
“Due to stress factors like lack of nutrition or host immune pressure, a small proportion of merozoites eventually develop into sexual precursor cells, the male and female gametocytes.”
BackgroundThe growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment
Saint-Léger, A., Sinadinos, C., & de Pouplana, L. R. (2016) · Bioengineered · doi:10.1080/21655979.2016.1149270 · Cited by 26
“genome and undertakes protein translation (harboring up to 30 self-coded proteins).(6) Aminoacyl-tRNA synthetases (aaRS), which catalyze the attachment of amino acids to their cognate tRNAs, are also good antimalarial drug targets and validated in the clinic.”
BackgroundActive site coupling in Plasmodium falciparum GMP synthetase is triggered by domain rotation
Ballut, L., Violot, S., Shivakumaraswamy, S., Thota, L., Sathya, M., Kunala, J., Dijkstra, B., Terreux, R., Haser, R., Balaram, H., et al. (2015) · Nature Communications · doi:10.1038/ncomms9930 · Cited by 27
Andreadaki, M., Morgan, R. N., Deligianni, E., Kooij, T., Santos, J. M., Spanos, L., Matuschewski, K., Louis, C., Mair, G., & Sidén-Kiamos, I. (2014) · Cellular Microbiology · doi:10.1111/cmi.12274 · Cited by 27
Kolevzon, N., Nasereddin, A., Naik, S., Yavin, E., & Dzikowski, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086802 · Cited by 27
Working in concert: the metalloaminopeptidases from Plasmodium falciparum.
McGowan, S. (2013) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2013.07.015 · Cited by 27
“PfMetAP1c contains an Nterminal signal peptide (in blue, SP) followed by a transit peptide domain (in green, T) to target the enzyme to the apicoplast [16].”
InfluentialAnalysis of Context-Dependent Errors for Illumina sequencing
Abnizova, I., Leonard, S., Skelly, T., Brown, A., Jackson, D. K., Gourtovaia, M., Qi, G., Boekhorst, I. R. J. A. T., Faruque, N., Lewis, K., et al. (2012) · J. Bioinform. Comput. Biol. · doi:10.1142/s0219720012410053 · Cited by 27
Identification of Putative Potassium Channel Homologues in Pathogenic Protozoa
Prole, D. L., & Marrion, N. V. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032264 · Cited by 34
Enderes, C., Kombila, D. U., Dal-Bianco, M. P., Dzikowski, R., Kremsner, P. G., & Frank, M. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir594 · Cited by 24
“UpsA and UpsB var genes are positioned subtelomerically, whereas UpsC var genes are located centrally [9, 10].”
BackgroundRenn, J. P., Doritchamou, J. Y. A., Tentokam, B. C. N., Morrison, R. D., Cowles, M. V., Burkhardt, M., Ma, R., Mahamar, A., Attaher, O., Diarra, B. S., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-02787-7 · Cited by 24
Aguttu, C., Okech, B., Mukisa, A. K., & Lubega, G. (2021) · Journal of Genetic Engineering and Biotechnology · doi:10.1186/s43141-021-00199-y · Cited by 26
Tonkin‐Hill, G. Q., Ruybal‐Pesántez, S., Tiedje, K. E., Rougeron, V., Duffy, M. F., Zakeri, S., Pumpaibool, T., Harnyuttanakorn, P., Branch, O. H., Mesía, L. R., et al. (2021) · PLoS Genetics · doi:10.1371/journal.pgen.1009269 · Cited by 24
Nofal, S. D., Patel, A., Blackman, M., Flueck, C., & Baker, D. (2020) · mBio · doi:10.1128/mbio.02694-20 · Cited by 26
“effector of cGMP signaling since canonical cGMP-gated ion channels are absent from the genome (4).”
Intra-host dynamics of co-infecting parasite genotypes in asymptomatic malaria patients
Nkhoma, S. C., Banda, R. L., Khoswe, S., Dzoole-Mwale, T. J., & Ward, S. A. (2018) · Infection Genetics and Evolution · doi:10.1016/j.meegid.2018.08.018 · Cited by 39
“…within malaria-infected blood samples assume that multiple-haplotype infections (MHIs) predominantly arise from superinfection such that their component parasite haplotypes are genetically unrelated and independent of each other (Hill and Babiker, 1995; Hill et al., 1995; Ross et al., 2012).”
BackgroundChêne, A., Gangnard, S., Dechavanne, C., Dechavanne, S., Srivastava, A., Tétard, M., Hundt, S., Leroy, O. Y., Havelange, N., Viebig, N. K., et al. (2018) · npj Vaccines · doi:10.1038/s41541-018-0064-6 · Cited by 36
Liu, Z.-W., Wang, Z.-Y., Gu, H., You, J., Hu, M.-L., Zhang, Y.-J., Zhu, Z., Wang, Y.-H., Liu, S.-J., Chen, L.-M., et al. (2018) · Frontiers in Plant Science · doi:10.3389/fpls.2018.00782 · Cited by 26
“Thus, the normal formation and development of chloroplasts is vital to sustain Abbreviations: ACP, acyl carrier protein; DAF, days after flowering; DAG, days after germination; ENR, enoyl-ACP reductase; FAS, fatty acid synthase, HAD, β-Hydroxyacyl-ACP dehydratase.”
BackgroundInfluentialHomologous Recombination in Protozoan Parasites and Recombinase Inhibitors
Kelso, A. A., Waldvogel, S. M., Luthman, A. J., & Sehorn, M. G. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01716 · Cited by 33
“LiRAD51 and LiBRCA2 both localize to punctate foci in the nucleus; however, LiRAD51 fails to localize to the nucleus in LiBRCA2-deficient cells (Genois et al., 2012).”
BackgroundSilberhorn, E., Schwartz, U., Löffler, P., Schmitz, S., Symelka, A., de Koning‐Ward, T. F., Merkl, R., & Längst, G. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1006080 · Cited by 43
“6% genome wide, but reaches up to 90% in introns and intergenic regions [1].”
BackgroundRizopoulos, Z., Matuschewski, K., & Haussig, J. M. (2016) · Infection and Immunity · doi:10.1128/iai.00148-16 · Cited by 36
“Several putative Plasmodium hemoproteins have been identified bioinformatically (7) or by studies of in vitro binding to recombinant proteins (6).”
BackgroundLymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria
Mandala, W. L., Msefula, C. L., Gondwe, E. N., Gilchrist, J. J., Graham, S. M., Pensulo, P., Mwimaniwa, G., Banda, M., Taylor, T. E., Molyneux, E., et al. (2015) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00564-15 · Cited by 28
“falciparum in 2002 (5) has led to greater insights into the biology of the malaria parasite, its antigenic variability, and its genetic diversity (6).”
BackgroundDNA-guided establishment of nucleosome patterns within coding regions of a eukaryotic genomePreprint
Beh, L. Y., Müller, M. M., Muir, T., Kaplan, N., & Landweber, L. (2015) · Genome Research · doi:10.1101/gr.188516.114 · Cited by 26
Prevalence and Diversity of Hepatozoon in Native and Exotic Geckos from Brazil
Harris, D., Borges-Nojosa, D. M., & Maia, J. (2015) · Journal of Parasitology · doi:10.1645/14-522.1 · Cited by 26
“Yet for some Apicomplexa, including Plasmodium Marchiafava and Celli, 1885 and the common and widespread Hepatozoon Miller, 1908, more species have been described from reptiles relative to other tetrapods (Smith, 1996).”
BackgroundInfluentialCDPKs of Cryptosporidium parvum—stage-specific expression in vitro
Etzold, M., Lendner, M., Daugschies, A., & Dyachenko, V. (2014) · Parasitology Research · doi:10.1007/s00436-014-3902-0 · Cited by 26
“Nested 3′ RACE-PCR”
BackgroundDevelopment of Plasmodium falciparum protease inhibitors in the past decade (2002-2012).
Pérez, B., Teixeira, C., Gomes, J. R. B., & Gomes, P. (2013) · Current Medicinal Chemistry · doi:10.2174/0929867311320250003 · Cited by 26
Protease-associated cellular networks in malaria parasite Plasmodium falciparum
Lilburn, T., Cai, H., Zhou, Z., & Wang, Y.-F. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-s5-s9 · Cited by 26
“…only about 20 proteins had been characterized; after genome sequencing this number increased by two orders of magnitude, but over 60% of the predicted gene products in the genome still had no functional assignment [18] and ten years of subsequent effort have reduced this number to roughly 45% [60].”
The primase domain of PfPrex is a proteolytically matured, essential enzyme of the apicoplast
Lindner, S., Llinás, M., Keck, J., & Kappe, S. (2011) · Molecular and biochemical parasitology (Print) · doi:10.1016/j.molbiopara.2011.08.002 · Cited by 26
“[2] Gardner MJ, Hall N, Fung E, et al.”
InfluentialPlatform for Plasmodium vivax vaccine discovery and development
Valencia, S. H., Rodríguez, D. C., Acero, D. L., Ocampo, V., & Arévalo‐Herrera, M. (2011) · Memórias do Instituto Oswaldo Cruz · doi:10.1590/s0074-02762011000900023 · Cited by 22
Molecular insights into artemisinin resistance in Plasmodium falciparum: An updated review.
Azmi, W. A., Rizki, A. F. M., Djuardi, Y., Artika, I., & Siregar, J. E. (2023) · Infection, Genetics and Evolution · doi:10.1016/j.meegid.2023.105460 · Cited by 25
In vitro production of infectious Plasmodium falciparum sporozoites
Eappen, A., Li, T., Marquette, M., Chakravarty, S., Kc, N., Zanghí, G., Hoffman, B., Hettiarachchi, H., Patil, A., Abebe, Y., et al. (2022) · Nature · doi:10.1038/s41586-022-05466-7 · Cited by 25
Self-citationHanhsen, B., Farrukh, A., Pradel, G., & Ngwa, C. J. (2022) · Cells · doi:10.3390/cells11101666 · Cited by 27
“falciparum 3D7 EPr1 [31]) with default parameters.”
Essential Genes of the Parasitic Apicomplexa
Oberstaller, J., Otto, T. D., Rayner, J. C., & Adams, J. H. (2021) · Trends in Parasitology · doi:10.1016/j.pt.2020.11.007 · Cited by 31
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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