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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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Functional control of a 0.5 MDa TET aminopeptidase by a flexible loop revealed by MAS NMR
Gauto, D. F., Macek, P., Malinverni, D., Fraga, H., Paloni, M., Sučec, I., Hessel, A., Bustamante, J. P., Barducci, A., & Schanda, P. (2021) · Nature Communications · doi:10.1038/s41467-022-29423-0 · Cited by 22
Madhav, H., & Hoda, N. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112955 · Cited by 38
STING or Sting: cGAS-STING-Mediated Immune Response to Protozoan Parasites
Sun, Y., & Cheng, Y. (2020) · Trends in Parasitology · doi:10.1016/j.pt.2020.07.001 · Cited by 27
Integrative Multi-Kinase Approach for the Identification of Potent Antiplasmodial Hits
Lima, M. N. N., Cassiano, G. C., Tomaz, K. C. P., Silva, A. C., Sousa, B. K. D. P., Ferreira, L. T., Tavella, T. A., Calit, J., Bargieri, D. Y., Neves, B. J., et al. (2019) · Frontiers in Chemistry · doi:10.3389/fchem.2019.00773 · Cited by 26
“falciparum (Gardner et al., 2002) has provided new and valuable information on its biological pathways, identifying potentially relevant biological targets for therapeutic intervention.”
BackgroundIs reliance on an inaccurate genome sequence sabotaging your experiments?
Baptista, R., & Kissinger, J. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007901 · Cited by 22
Healer, J., Chiu, C. Y. H., & Hansen, D. S. (2017) · Parasitology · doi:10.1017/s0031182017001949 · Cited by 26
“Whilst early studies had mainly focussed on a few merozoite antigens identified as potential vaccine candidates, the availability of the genome (Gardner et al. 2002), transcriptome (Bozdech et al. 2003; Le Roch et al. 2003) and proteome (Florens et al. 2002) of P. falciparum provided the…”
BackgroundSteady progress toward a malaria vaccine
Lyke, K. E. (2017) · Current Opinion in Infectious Diseases · doi:10.1097/qco.0000000000000393 · Cited by 23
Abdi, A., Kariuki, S. M., Muthui, M., Kivisi, C. A., Fegan, G., Gitau, E., Newton, C., & Bull, P. (2015) · Scientific Reports · doi:10.1038/srep18034 · Cited by 22
Malaria vaccines: identifying Plasmodium falciparum liver-stage targets
Longley, R. J., Hill, A. V. S., & Spencer, A. J. (2015) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.00965 · Cited by 25
“The discovery of the Plasmodium genome (Gardner et al., 2002) and proteome (Florens et al., 2002) has yielded a huge number of potential liver-stage targets, but has not necessarily provided information as to which should or could be included in a vaccine.”
BackgroundMcGillewie, L., & Soliman, M. (2015) · Proteins: Structure, Function, and Bioinformatics · doi:10.1002/prot.24855 · Cited by 22
Targeting the gyrase of Plasmodium falciparum with topoisomerase poisons
Girdwood, S. C. T., Nenortas, E., & Shapiro, T. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.03.018 · Cited by 22
Madkhali, A. M., Alkurbi, M. O., Szestak, T., Bengtsson, A., Patil, P. R., Wu, Y., Al-Harthi, S. A., Jensen, A. T. R., Pleass, R. J., & Craig, A. G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111518 · Cited by 23
“A typical PfEMP-1 structure consists of two to seven Duffy-binding– like (DBL) domains and one to two cysteine-rich interdomain region (CIDR) domains [32].”
BackgroundSelf-citationRussell, K., Hasenkamp, S., Emes, R. D., & Horrocks, P. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-267 · Cited by 22
“[17], we know relatively little regarding the fundamental organisation of the transcriptional unit in this important pathogen.”
Generation of second messengers in Plasmodium.
Budu, A., & Garcia, C. R. S. (2012) · Microbes and infection · doi:10.1016/j.micinf.2012.04.012 · Cited by 22
Nacer, A., Roux, E., Pomel, S., Scheidig-Benatar, C., Sakamoto, H., Lafont, F., Scherf, A., & Mattei, D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0029039 · Cited by 22
“The var genes share a two exon structure with exon 1 coding for the extracellular highly variable adhesive region and a conserved cytoplasmic exon 2 that codes for a transmembrane region (TM) and interacts with the red blood cell cytoskeleton [4].”
BackgroundProteases in Malaria Parasites - A Phylogenomic Perspective
Cai, H., Kuang, R., Gu, J., & Wang, Y. (2011) · Current Genomics · doi:10.2174/138920211797248565 · Cited by 23
Groussman, R. D., Blaskowski, S., Coesel, S., & Armbrust, E. V. (2023) · Scientific Data · doi:10.1038/s41597-023-02842-4 · Cited by 31
Lyons, F. M. T., Gabriela, M., Tham, W., & Dietrich, M. H. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.945924 · Cited by 23
“falciparum proteins, namely Pf36, Pf52, PfLISP2, PfB9, Pf12, Pf12p, Pf41, Pf38, Pf92, Pfs48/45, Pfs230, Pfs230p, Pfs47 and PfPSOP12 (Figure 1A) (Templeton and Kaslow, 1999; Kappe et al., 2001; Thompson et al., 2001; Gardner et al., 2002; Gerloff et al., 2005; Arredondo et al., 2012; Orito et al., 2013; Annoura et al.,…”
Doritchamou, J., Renn, J. P., Jenkins, B. J., Mahamar, A., Dicko, A., Fried, M., & Duffy, P. E. (2022) · eLife · doi:10.7554/elife.76264 · Cited by 24
Lyke, K., Singer, A., Berry, A. A., Reyes, S., Chakravarty, S., James, E., Billingsley, P., Gunasekera, A., Manoj, A., Murshedkar, T., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1294 · Cited by 21
Self-citationDecoding the complexities of human malaria through systems immunology
Tran, T. M., & Crompton, P. D. (2019) · Immunological Reviews · doi:10.1111/imr.12817 · Cited by 25
Commit, hide and escape: the story ofPlasmodiumgametocytes
Beri, D., Balan, B., & Tatu, U. S. (2018) · Parasitology · doi:10.1017/s0031182018000926 · Cited by 41
Host immune evasion strategies of malaria blood stage parasite
Yam, X. Y., & Preiser, P. R. (2017) · Molecular BioSystems · doi:10.1039/c7mb00502d · Cited by 26
González-Bacerio, J., Maluf, S. E. C., Méndez, Y., Pascual, I., Florent, I., Melo, P. M., Budu, A., Ferreira, J. C., Moreno, E., Carmona, A. K., et al. (2017) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2017.06.047 · Cited by 21
Pre-clinical and clinical development of the first placental malaria vaccine
Pehrson, C., Salanti, A., Theander, T. G., & Nielsen, M. A. (2017) · Expert Review of Vaccines · doi:10.1080/14760584.2017.1322512 · Cited by 31
Novel inhibitors of Plasmodium falciparum based on 2,5-disubstituted furans.
Krake, S. H., Martinez, P. D. G., McLaren, J. M., Ryan, E., Gong, C., White, K., Charman, S., Campbell, S., Willis, P., & Dias, L. (2017) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2016.12.024 · Cited by 21
Sugiura, N., Clausen, T. M., Shioiri, T., Gustavsson, T., Watanabe, H., & Salanti, A. (2016) · Glycoconjugate Journal · doi:10.1007/s10719-016-9685-z · Cited by 26
Illuminating Parasite Protein Production by Ribosome Profiling
Parsons, M., & Myler, P. J. (2016) · Trends in Parasitology · doi:10.1016/j.pt.2016.03.005 · Cited by 20
“Even though two-thirds of the CDSs were originally annotated in PlasmoDB as ‘hypothetical proteins’ [28,29], only 40% of the 5398 protein-coding genes are currently annotated as having unknown function.”
Jeppesen, A., Ditlev, S. B., Soroka, V., Stevenson, L., Turner, L., Dzikowski, R., Hviid, L., & Barfod, L. K. (2015) · Infection and Immunity · doi:10.1128/iai.00337-15 · Cited by 28
Normalizing Kernels in the Billera-Holmes-Vogtmann Treespace
Weyenberg, G., Yoshida, R., & Howe, D. (2015) · IEEE/ACM Transactions on Computational Biology & Bioinformatics · doi:10.1109/tcbb.2016.2565475 · Cited by 21
Lam, K. N., & Charles, T. C. (2015) · Microbiome · doi:10.1186/s40168-015-0086-5 · Cited by 21
“It was reported that there are difficulties associated with cosmid cloning of very AT-rich genomic DNA [26, 27], and even when genomic libraries can be constructed, cosmid clones may be unstable [28–31], which simply means that foreign DNA fragments are not able to be maintained in the E.”
BackgroundA large-scale proteogenomics study of apicomplexan pathogens—Toxoplasma gondii and Neospora caninum
Krishna, R., Xia, D., Sanderson, S., Shanmugasundram, A., Vermont, S., Bernal, A., Daniel-Naguib, G., Ghali, F., Brunk, B., Roos, D., et al. (2015) · Proteomics · doi:10.1002/pmic.201400553 · Cited by 21
“Among the first resources available at EuPathDB (formerly known as ApiDB back in 2005) was the genome of Plasmodium falciparum, which was the first apicomplexan genome to be sequenced [4].”
BackgroundSelf-citationSwanepoel, C. C., & Loots, D. T. (2014) · Disease Markers · doi:10.1155/2014/124218 · Cited by 17
“[50] subsequently illustrated the same phenomenon in Plasmodium falciparum, the causative agent of malaria [51], using a similar metabolomics approach.”
Method
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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