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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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Discovery of Small-Molecule Allosteric Inhibitors of Pf ATC as Antimalarials
Wang, C., Zhang, B., Krüger, A., Du, X., Visser, L., Dömling, A. S. S., Wrenger, C., & Groves, M. R. (2022) · Journal of the American Chemical Society · doi:10.1021/jacs.2c08128 · Cited by 24
Kanai, M., Yeo, T., Asua, V., Rosenthal, P., Fidock, D., & Mok, S. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01163-21 · Cited by 17
“WGS genotyping does not need a positive control strain (e.g., 3D7) for each run, can identify the genomic location of microsatellite insertions and deletions, and can assess a much larger number of microsatellites (74).”
InfluentialHoo, R., Bruske, E. I., Dimonte, S., Zhu, L., Mordmüller, B. G., Sim, B. K. L., Kremsner, P. G., Hoffman, S. L., Bozdech, Z., Frank, M., et al. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.09.001 · Cited by 27
“All the changes the parasite undergoes during its complex life cycle are controlled by about 5000 protein-coding genes within the malaria parasite genome [11].”
BackgroundSelf-citationShen, H.-M., Chen, S.-B., Cui, Y.-B., Xu, B., Kassegne, K., Abe, E., Wang, Y., & Chen, J.-H. (2018) · Infectious Diseases of Poverty · doi:10.1186/s40249-018-0493-5 · Cited by 17
“Whole genome studies provide us with the opportunity to develop new control methods, including new drugs and vaccines, improved diagnostics and effective vector control techniques [9].”
BackgroundPereira, S. S., Casas-Sánchez, A., Haines, L., Ogugo, M., Absolomon, K., Sanders, M., Kemp, S., Acosta-Serrano, Á., Noyes, H., Berriman, M., et al. (2018) · Genome Research · doi:10.1101/gr.234146.118 · Cited by 17
“Functional differentiation is also seen in P. falciparum var genes (Gardner et al. 2002; Kraemer and Smith 2003; Lavstsen et al. 2003).”
BackgroundSelf-citationCastillo, A. I., Nelson, A. D. L., Haug-Baltzell, A., & Lyons, E. (2018) · Database J. Biol. Databases Curation · doi:10.1093/database/bay030 · Cited by 17
Exploiting the apicoplast: apicoplast-targeting drugs and malaria vaccine development.
Low, L. M., Stanisic, D., & Good, M. (2017) · Microbes and infection · doi:10.1016/j.micinf.2017.12.005 · Cited by 17
Mogire, R. M., Akala, H. M., Macharia, R. W., Juma, D. W., Cheruiyot, A. C., Andagalu, B., Brown, M. L., El‐Shemy, H. A., & Nyanjom, S. G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0186364 · Cited by 25
Fodjo, B. A. Y., Atemnkeng, N., Esemu, L. F., Yuosembom, E. K., Quakyi, I. A., Tchinda, V. H. M., Smith, J. D., Salanti, A., Bigoga, J. D., Taylor, D. W., et al. (2016) · Malaria Journal · doi:10.1186/s12936-016-1585-y · Cited by 18
Ganter, M., Rizopoulos, Z., Schüler, H., & Matuschewski, K. (2015) · Molecular Microbiology · doi:10.1111/mmi.12922 · Cited by 17
“Surprisingly, and in contrast to other eukaryotes, near-complete genome data sets (Gardner et al ., 2002) suggested that the dynamics of these short actin filaments are regulated only by a minimal set of binding proteins (Baum et al ., 2006; Schüler and Matuschewski, 2006; Sattler et al ., 2011).”
Kirkman, L., & Deitsch, K. (2014) · Microbiology spectrum · doi:10.1128/microbiolspec.mdna3-0022-2014 · Cited by 17
“In the case of Plasmodium, being surrounded by the membrane of a host cell that is largely metabolically inactive renders the parasites almost entirely hidden from circulating antibodies, thus enabling them to mostly avoid this arm of the immune response.”
BackgroundInfluentialPlasmodium genome in blood donors at risk for malaria after several years of residence in Italy
Assennato, S. M., Berzuini, A., Foglieni, B., Spreafico, M., Allain, J., & Prati, D. (2014) · Transfusion · doi:10.1111/trf.12650 · Cited by 17
“It is recognized that approximately five copies of the genome are present per infected red blood cell.(15)”
BackgroundInhibition and Structure of Toxoplasma gondii Purine Nucleoside Phosphorylase
Donaldson, T., Cassera, M., Ho, M., Zhan, C., Merino, E., Evans, G. B., Tyler, P., Almo, S., Schramm, V., & Kim, K. (2014) · Eukaryotic Cell · doi:10.1128/ec.00308-13 · Cited by 17
A Novel Malaria Vaccine Candidate Antigen Expressed in Tetrahymena thermophila
Cowan, G., Bockau, U., Eleni-Muus, J., Aldag, I., Samuel, K., Creasey, A., Hartmann, M., & Cavanagh, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087198 · Cited by 17
“falciparum, such as similar codon usage bias and the production of a number of large and structurally complex proteins [11,12].”
BackgroundA Nondiscriminating Glutamyl-tRNA Synthetase in the Plasmodium Apicoplast
Mailu, B. M., Ramasamay, G., Mudeppa, D. G., Li, L., Lindner, S., Peterson, M. J., DeRocher, A., Kappe, S., Rathod, P., & Gardner, M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.507467 · Cited by 17
“berghei cell-free extracts (89), and genome sequencing later revealed the entire complement of aaRSs in Plasmodium (10, 68, 88).”
BackgroundMethodInfluentialSelf-citationDalal, S. R., Ragheb, D. R. T., Schubot, F. D., & Klemba, M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.465625 · Cited by 22
“falciparum (28), which was the source of the PfAM1 sequence used in this study, indicates that a”
MethodLemaitre, C., Barré, A., Citti, C., Tardy, F., Thiaucourt, F., Sirand-Pugnet, P., & Thébault, P. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-457 · Cited by 17
“Additionally, at the scale of the whole genome, some species show extreme nucleotide compositions that affect their amino acid composition, one of the most extreme example being the malaria agent, Plasmodium falciparum, with a 80%- A+T genome [3].”
BackgroundCharacterization of the Duffy-Binding-Like Domain of Plasmodium falciparum Blood-Stage Antigen 332
Nilsson, S. K., Moll, K., Angeletti, D., Albrecht, L., Kursula, I., Jiang, N., Sun, X.-D., Berzins, K., Wahlgren, M., & Chen, Q.-J. (2011) · Malaria Research and Treatment · doi:10.4061/2011/671439 · Cited by 17
“The anti-Pf332 antibodies did not bind to any of the EBA175 peptides, indicating that they do not cross-react with linear epitopes of the EBL-DBLs (see Supplementary Figure1 available online at doi: 10.4061/2011/671439).”
BackgroundInfluentialWichers, J. S., Mesén-Ramírez, P., Fuchs, G., Yu-Strzelczyk, J., Stäcker, J., von Thien, H., Alder, A., Henshall, I., Liffner, B., Nagel, G., et al. (2022) · mBio · doi:10.1128/mbio.00623-22 · Cited by 16
Higgins, M. K. (2008) · Acta Crystallographica Section F Structural Biology and Crystallization Communications · doi:10.1107/s1744309108004211 · Cited by 16
Singh, M. K., Bonnell, V. A., da Silva, I. T., Santiago, V. F., Moraes, M. S., Adderley, J., Doerig, C., Palmisano, G., Llinás, M., & Garcia, C. R. S. (2024) · bioRxiv · doi:10.7554/elife.92201 · Cited by 16
“The gene regulatory toolbox in malaria parasites is lacking many transcriptional regulatory factors conserved in other eukaryotes ( Gardner et al., 2002 ).”
BackgroundThe genetic landscape of origins of replication in P. falciparum
Castellano, C. M., Lacroix, L., Mathis, E., Prorok, P., Hennion, M., Lopez-Rubio, J.-J., Méchali, M., & Gomes, A. R. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1103 · Cited by 16
“Although phylogenetic analysis indicate that all six ORC sub-units are likely present in the Plasmodium genome ( 45 ,46 ), we chose to focus on those two since the C-terminal region of both Pf ORC1 and Pf ORC2 were shown to be functional in S. cerevisiae complementation studies ( 47 ,48 ).”
BackgroundInfluentialMechanism of Immune Evasion in Mosquito-Borne Diseases
Bhattacharjee, S., Ghosh, D., Saha, R., Sarkar, R., Kumar, S., Khokhar, M., & Pandey, R. K. (2023) · Pathogens · doi:10.3390/pathogens12050635 · Cited by 22
“There are approximately 60 var genes that express PfEMP1 [77] on RBC surfaces [78].”
BackgroundInfluentialCRISPR-Cas13 in malaria parasite: Diagnosis and prospective gene function identification
Quansah, E., Chen, Y., Yang, S., Wang, J., Sun, D., Zhao, Y., Chen, M., Li, Y., & Zhang, C. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1076947 · Cited by 17
Pipaliya, S. V., Santos, R., Salas-Leiva, D. E., Balmer, E. A., Wirdnam, C. D., Roger, A. J., Hehl, A. B., Faso, C., & Dacks, J. B. (2021) · BMC Biology · doi:10.1186/s12915-021-01077-2 · Cited by 25
Telomere length dynamics in response to DNA damage in malaria parasites
Reed, J., Kirkman, L., Kafsack, B. F. C., Mason, C., & Deitsch, K. (2020) · bioRxiv · doi:10.1101/2020.11.08.373563 · Cited by 16
“Their function has not been defined, although they are known to transcribe long noncoding RNAs [10, 11] and have been hypothesized to play a role in the subnuclear positioning of the chromosome ends, thus possibly contributing to subtelomeric recombination events [5].”
BackgroundGbédandé, K., Carpio, V. H., & Stephens, R. (2020) · Immunological Reviews · doi:10.1111/imr.12835 · Cited by 20
Deciphering host immunity to malaria using systems immunology
Loiseau, C., Cooper, M. M., & Doolan, D. L. (2019) · Immunological Reviews · doi:10.1111/imr.12814 · Cited by 23
Erath, J., Djuranović, S., & Djuranovic, S. P. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02823 · Cited by 15
Xu, R., Liu, Y., Fan, R., Liang, R., Yue, L., Liu, S., Su, X., & Li, J. (2019) · International Journal for Parasitology · doi:10.1016/j.ijpara.2019.04.003 · Cited by 18
Mura, M., Ruffié, C., Combredet, C., Aliprandini, E., Formaglio, P., Chitnis, C., Amino, R., & Tangy, F. (2019) · npj Vaccines · doi:10.1038/s41541-019-0106-8 · Cited by 16
Bohaliga, G. A. R., Johnson, W., Taus, N., Hussein, H., Bastos, R., Suárez, C., O'Connor, R. M., & Ueti, M. (2018) · Parasites & Vectors · doi:10.1186/s13071-018-3052-9 · Cited by 16
Malaria Transmission-Blocking Vaccines: Present Status and Future Perspectives
Doumbo, O. K., Niaré, K., Healy, S. A., Sagara, I., & Duffy, P. E. (2018) · InTech eBooks · doi:10.5772/intechopen.77241 · Cited by 20
“falciparum, a protozoan parasite characterized by three genomes (nuclear, mitochondrial, and apicoplastid), an adenine-thymine rich (~80%) nuclear genome [16] encoding >5000 genes, and a complex lifecycle involving several developmental stages between vertebrate and invertebrate hosts.”
BackgroundGene copy number variation in natural populations of Plasmodium falciparum in Eastern Africa
Simam, J., Rono, M. K., Ngoi, J. M., Nyonda, M. A., Mok, S., Marsh, K., Bozdech, Z., & Mackinnon, M. J. (2018) · BMC Genomics · doi:10.1186/s12864-018-4689-7 · Cited by 22
“falciparum genome sequence of 3D7 parasite line [62] targeting conserved regions of approximately 5400 genes with an average of two probes per gene [59].”
Amlabu, E., Mensah-Brown, H., Nyarko, P. B., Akuh, O.-A., Opoku, G., Ilani, P., Oyagbenro, R. K., Asiedu, K., Aniweh, Y., & Awandare, G. (2018) · Journal of Infectious Diseases · doi:10.1093/infdis/jiy222 · Cited by 16
“falciparum genome sequencing project was that nearly 60% of the parasite’s genes lacked sequence similarity to genes from other known organisms, and thus these genes have remained hypothetical with no defined functional roles [13].”
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“falciparum erythrocyte membrane protein 1 (PfEMP1) [3–5], encoded by the multicopy var gene family, which consists of approximately 60 different var genes [6].”
BackgroundSelf-citationSelective anti-malarial minor groove binders.
Scott, F. J., Khalaf, A., Duffy, S., Avery, V. M., & Suckling, C. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.05.039 · Cited by 16
“Overall, five of the most active compounds, all alkene linked, contained a C-alkylthiazole (18-21, 22, 23, 25).”
InfluentialModelling the Effects of Mass Drug Administration on the Molecular Epidemiology of Schistosomes
Lamberton, P. H. L., Crellen, T., Cotton, J. A., & Webster, J. P. (2015) · Advances in Parasitology/Advances in parasitology · doi:10.1016/bs.apar.2014.12.006 · Cited by 38
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Revisiting the multigene families: Plasmodium var and vir genes.
Singh, V., Gupta, P., & Pande, V. (2014) · Journal of Vector Borne Diseases · doi:10.4103/0972-9062.134773 · Cited by 16
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“This number is relatively small when compared to estimates for Toxoplasma (17,000 genes) [9] and Plasmodium (5,268 genes) [7].”
ResultCrystal structure of a macrophage migration inhibitory factor from Giardia lamblia
Buchko, G. W., Abendroth, J. A., Robinson, H. H., Zhang, Y., Hewitt, S. N., Edwards, T. E., Voorhis, W. C. V., & Myler, P. J. (2013) · Journal of Structural and Functional Genomics · doi:10.1007/s10969-013-9155-9 · Cited by 17
“Interestingly, DNA coding for MIF proteins have been identified in the sequenced genomes of some other protozoan parasites, including Plasmodium falciparum, the etiological agent responsible for malaria [32].”
BackgroundNeves, B. J., Bueno, R. V., Braga, R. C., & Andrade, C. H. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.02.006 · Cited by 14
Malaria vaccine can prevent millions of deaths in the world
Verma, R., Khanna, P., & Chawla, S. (2013) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.23950 · Cited by 16
The effects of symmetry on the dynamics of antigenic variation
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“For the malaria agent P. falciparum, the main target of immune response is Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1), which is expressed from a diverse family of var genes, and each parasite genome contains approximately 60 var genes encoding different PfEMP1 variants [25].”
BackgroundPlasmodium falciparum MLH is schizont stage specific endonuclease
Tarique, M., Satsangi, A. T., Ahmad, M., Singh, S., & Tuteja, R. (2011) · Molecular and Biochemical Parasitology · doi:10.1016/j.molbiopara.2011.10.012 · Cited by 22
Molecular parasitology in the 21st Century
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“Parasitism typically entails strong selective pressure for genome reduction, and this is particularly evident in P. falciparum whose genome is small even compared to other apicomplexans 54,55 .”
Neutral vs. non-neutral genetic footprints of Plasmodium falciparum multiclonal infections
Labbé, F., He, Q., Qi, Z., Tiedje, K. E., Argyropoulos, D. C., Tan, M. H., Ghansah, A., Day, K. P., & Pascual, M. (2023) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1010816 · Cited by 31
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The Absence of C-5 DNA Methylation in Leishmania donovani Allows DNA Enrichment from Complex Samples
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Metabolomic changes in vertebrate host during malaria disease progression
Ghosh, S., Pathak, S., Sonawat, H. M., Sharma, S., & Sengupta, A. (2018) · Cytokine · doi:10.1016/j.cyto.2018.07.022 · Cited by 15
Does the MHC Confer Protection against Malaria in Bonobos?
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Distinct genomic architecture of Plasmodium falciparum populations from South Asia
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“falciparum, proved to be an unprecedented asset for malaria scientists [1].”
BackgroundAntony, H., Pathak, V., Parija, S., Ghosh, K., & Bhattacherjee, A. (2016) · Omics · doi:10.1089/omi.2016.0058 · Cited by 15
“This WGS analysis resulted in the iden-tification of * 5400 genes present in the genome, of which more than 60% of the predicted genes encoding for proteins lack sequence similarity or orthologs in other different organisms (Gardner et al., 2002).”
InfluentialProfiling the host response to malaria vaccination and malaria challenge
Dunachie, S. J., Hill, A. V. S., & Fletcher, H. A. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.07.107 · Cited by 18
“[9], and this parasite diversity contributes to the slow speed of acquisition of natural immunity [10].”
BackgroundMailu, B. M., Li, L., Arthur, J., Nelson, T. M., Ramasamy, G., Fritz-Wolf, K., Becker, K., & Gardner, M. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.655100 · Cited by 15
“We did not test whether PfGatAB possesses Asp-AdT activity as bacterial GatCABs do because the Plasmodium genome possesses two predicted AspRSs, one cytoplasmic and the other apicoplast-targeted (11, 25, 56, 62), as well as an apicoplasttargeted AsnRS.”
BackgroundMethodInfluentialSelf-citationDoritchamou, J., Sossou-tchatcha, S., Cottrell, G., Moussiliou, A., Houngbeme, C. H., Massougbodji, A., Deloron, P., & Ndam, N. T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098577 · Cited by 16
“The best-characterized adhesion ligands expressed on the surface of IE are members of the highly polymorphic Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP-1) family, encoded by the var gene family [5].”
BackgroundSubudhi, A., Boopathi, P. A., Garg, S., Middha, S., Acharya, J., Pakalapati, D., Saxena, V., Aiyaz, M., Orekondy, H. B., Mugasimangalam, R., et al. (2014) · Experimental parasitology · doi:10.1016/j.exppara.2014.03.008 · Cited by 15
Molecular Diagnosis of Vector-Borne Parasitic Diseases
Hernández, C., & Ramírez, J. (2013) · doi:10.4172/2167-7719.1000110 · Cited by 15
Lima, W. R., Holder, A. A., & Garcia, C. R. S. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140713704 · Cited by 13
“falciparum genome sequence was determined ten years ago [11] since when many protein families have been discovered and characterized [12,13].”
BackgroundPfHPRT: A New Biomarker Candidate of Acute Plasmodium falciparum Infection
Thézénas, M. L., Huang, H., Njie, M., Ramaprasad, A., Nwakanma, D. C., Fischer, R., di Gleria, K., Walther, M. R., Conway, D. J., Kessler, B. M., et al. (2013) · Journal of Proteome Research · doi:10.1021/pr300858g · Cited by 20
Antimalarial drug discovery: where next?
Burrows, J. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.189 · Cited by 15
Li, Zong, Ji, Zhao, & Wei (2012) · Biomedical and environmental sciences : BES · doi:10.3967/0895-3988.2012.06.015 · Cited by 15
Determination of protein subcellular localization in apicomplexan parasites.
Woodcroft, B., McMillan, P., Dekiwadia, C., Tilley, L., & Ralph, S. A. (2012) · Trends in Parasitology · doi:10.1016/j.pt.2012.08.008 · Cited by 15
Self-citationEpidemiology - Current Perspectives on Research and Practice
Lunet, N. (2012) · InTech eBooks · doi:10.5772/2241 · Cited by 15
Genomics reveals heterogeneous Plasmodium falciparum transmission and selection signals in Zambia
Fola, A. A., He, Q., Xie, S., Thimmapuram, J., Bhide, K. P., Dorman, J., Ciubotariu, I. I., Mwenda, M., Mambwe, B., Mulube, C., et al. (2024) · Communications Medicine · doi:10.1038/s43856-024-00498-8 · Cited by 16
Decoding the impact of nuclear organization on antigenic variation in parasites
Barcons-Simon, A., Carrington, M., & Siegel, T. (2023) · Nature Microbiology · doi:10.1038/s41564-023-01424-9 · Cited by 14
Craven, H. M., Nettesheim, G., Cicuta, P., Blagborough, A. M., & Merrick, C. J. (2023) · International Journal for Parasitology Drugs and Drug Resistance · doi:10.1016/j.ijpddr.2023.11.007 · Cited by 14
“P. falciparum has a highly A/T-biased genome (~81% A/T) (Gardner et al., 2002) with very few sequences that have the potential to form G4s (‘PQSs ’ ); nevertheless, we and others have shown that these G4s do exist and that they play roles in Plasmodium biology at both the DNA (Gage and Merrick,…”
BackgroundInfluentialMorano, A. A., Rudlaff, R. M., & Dvorin, J. D. (2023) · Nature Communications · doi:10.1038/s41467-023-39435-z · Cited by 15
Rizvi, Z., Reddy, G., Gorde, S. M., Pundir, P., Das, D., & Sijwali, P. (2023) · bioRxiv · doi:10.1371/journal.ppat.1012045 · Cited by 14
Ribosome heterogeneity and specialization of Plasmodium parasites
McGee, J. P., Armache, J., & Lindner, S. (2023) · PLoS Pathogens · doi:10.1371/journal.ppat.1011267 · Cited by 14
“8S-28S pre-rRNA, which are located on different chromosomes [2,20,21].”
BackgroundThe role of Long Non-Coding RNAs in malaria parasites
Thompson, T. A., Chahine, Z., & Roch, K. L. L. (2023) · Trends in Parasitology · doi:10.1016/j.pt.2023.03.016 · Cited by 14
A unique symbiosome in an anaerobic single-celled eukaryote
Jerlström-Hultqvist, J., Gallot-Lavallée, L., Salas-Leiva, D. E., Curtis, B. A., Záhonová, K., Čepička, I., Stairs, C. W., Pipaliya, S. V., Dacks, J. B., Archibald, J. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54102-7 · Cited by 19
“The nuclear genomes of Anaeramoebae are A+T-rich, with the A. ignava BMAN nuclear genome (80.65% A+T) and intron (91.86% A+T) sequences being among the highest ever reported in eukaryotes (see for example; P. falciparum A+T genome (80.6%), intron (86.5%)(Gardner et al. 2002)) (Table S1,S3A).”
BackgroundInfluentialA non-canonical sensing pathway mediates Plasmodium adaptation to amino acid deficiency
Marreiros, I. M., Marques, S., Parreira, A., Mastrodomenico, V., Mounce, B. C., Harris, C. T., Kafsack, B. F. C., Billker, O., Zuzarte‐Luís, V., & Mota, M. M. (2023) · Communications Biology · doi:10.1038/s42003-023-04566-y · Cited by 21
Markwalter, C. F., Menya, D., Wesolowski, A., Esimit, D., Lokoel, G., Kipkoech, J., Freedman, E., Sumner, K. M., Abel, L., Ambani, G., et al. (2022) · PLOS Global Public Health · doi:10.1371/journal.pgph.0000807 · Cited by 22
Mitochondrially targeted proximity biotinylation and proteomic analysis in Plasmodium falciparum
Lamb, I. M., Rios, K. T., Shukla, A., Ahiya, A. I., Morrisey, J. M., Mell, J., Lindner, S., Mather, M., & Vaidya, A. (2022) · bioRxiv · doi:10.1371/journal.pone.0273357 · Cited by 14
“falciparum genome annotation, we predicted at least 148 nuclear-encoded proteins were targeted to the mitochondrion based upon homology [25].”
MethodSelf-citationApicoplast Dynamics During Plasmodium Cell Cycle
Elaagip, A. H., Absalon, S., & Florentin, A. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.864819 · Cited by 21
“falciparum in 2002 (Gardner et al., 2002), various surveys on population genetics, genomics, transcriptomics and proteomics brought into view the potential of targeting parasitespecific molecular pathways in eliminating malaria (Winzeler, 2008; Su et al.”
BackgroundSynthesis and antiplasmodial assessment of nitazoxanide and analogs as new antimalarial candidates
Irabuena, C., Scarone, L., de Souza, G., Aguiar, A. C. C., Mendes, G. R., Guido, R. V. C., & Serra, G. L. (2022) · Medicinal Chemistry Research · doi:10.1007/s00044-021-02843-1 · Cited by 16
“falciparum (human malaria parasite) [57], and P.”
Han, J.-R., Munro, J., Kocoski, A., Barry, A. E., & Bahlo, M. (2022) · PLoS Genetics · doi:10.1371/journal.pgen.1009604 · Cited by 14
Shah, Z., Naung, M. T., Moser, K., Adams, M., Buchwald, A. G., Dwivedi, A., Ouattara, A., Seydel, K., Mathanga, D., Barry, A. E., et al. (2020) · medRxiv · doi:10.1371/journal.pgen.1009576 · Cited by 14
The highly diverse TATA box-binding proteins among protists: A review.
Parra-Marín, O., López-Pacheco, K., Hernández, R., & López-Villaseñor, I. (2020) · Molecular and biochemical parasitology (Print) · doi:10.1016/j.molbiopara.2020.111312 · Cited by 14
Defining multiplicity of vector uptake in transfected Plasmodium parasites
Carrasquilla, M., Adjalley, S. H., Sanderson, T., Marín-Menéndez, A., Coyle, R., Montandon, R., Rayner, J. C., Pance, A., & Lee, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-67791-z · Cited by 17
Role of PfGCN5 in nutrient sensing and transcriptional regulation in Plasmodium falciparum
Rawat, M., Malhotra, R., Shintre, S., Pani, S., & Karmodiya, K. (2020) · Journal of Biosciences · doi:10.1007/s12038-019-9981-4 · Cited by 12
Liu, F., Liu, Q., Yu, C.-Y., Zhao, Y., Wu, Y., Min, H., Qiu, Y., Jin, Y., Miao, J., Cui, L.-W., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02193 · Cited by 14
“The deciphering of Plasmodium genomes has provided an unprecedented opportunity for large-scale functional studies toward a better understanding of the fundamental developmental biology of the parasite (Gardner et al., 2002; Hall et al., 2005).”
BackgroundValenciano, A., Fernández-Murga, M., Merino, E., Holderman, N. R., Butschek, G. J., Shaffer, K. J., Tyler, P., & Cassera, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-50319-5 · Cited by 14
Identification of proteins expressed by Babesia bigemina kinetes
Bohaliga, G. A. R., Johnson, W., Taus, N., Hussein, H., Bastos, R., Suárez, C., Scoles, G., & Ueti, M. (2019) · Parasites & Vectors · doi:10.1186/s13071-019-3531-7 · Cited by 14
Paight, C., Slamovits, C. H., Saffo, M. B., & Lane, C. E. (2018) · Genome Biology and Evolution · doi:10.1093/gbe/evy251 · Cited by 17
“Nephromyces was misclassified as a fungus for more than a 100 years, based on long hyphal-like cell structures, flagellated spores interpreted by some as chytrid zoospores and cell walls made of a chitin (Giard 1888).”
BackgroundPre-clinical evaluation of a P. berghei-based whole-sporozoite malaria vaccine candidate
Mendes, A., Reuling, I. J., Andrade, C. M., Otto, T., Machado, M., Teixeira, F., Pissarra, J., Gonçalves-Rosa, N., Bonaparte, D., Sinfrónio, J., et al. (2018) · npj Vaccines · doi:10.1038/s41541-018-0091-3 · Cited by 14
Self-citationDisruption of the RNA exosome reveals the hidden face of the malaria parasite transcriptome
Droll, D., Wei, G.-Y., Guo, G.-Q., Fan, Y.-T., Baumgarten, S., Zhou, Y.-Q., Xiao, Y., Scherf, A., & Zhang, Q.-F. (2018) · RNA Biology · doi:10.1080/15476286.2018.1517014 · Cited by 14
“org, v3 release 28) [25] using ‘bwamem’ [36] allowing only unique read mappings to the genome (option -c 1).”
MethodRaza, M., Khan, Z., Ahmad, A., Raza, S., Khan, A., Mohammadzai, I., & Zada, S. (2017) · Comput. Biol. Chem. · doi:10.1016/j.compbiolchem.2017.09.002 · Cited by 14
The Promise of Systems Biology Approaches for Revealing Host Pathogen Interactions in Malaria
Zuck, M., Austin, L. S., Danziger, S. A., Aitchison, J. D., & Kaushansky, A. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02183 · Cited by 26
“The genome of the Plasmodium parasite was initially published in 2002 (Gardner et al., 2002), and has been refined since.”
Schussek, S., Trieu, A., Apte, S., Sidney, J., Sette, A., & Doolan, D. (2017) · Scientific Reports · doi:10.1038/s41598-017-15354-0 · Cited by 14
Ubhe, S., Rawat, M., Verma, S. P., Anamika, K., & Karmodiya, K. (2017) · BMC Genomics · doi:10.1186/s12864-017-4052-4 · Cited by 32
“Of the 23 Mb nucleotide genome, 53% constitutes coding while the remaining 47% is predicted to be non-coding DNA (ncDNA) [2].”
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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