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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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“Robust Determination of Copy Number Variation The P. falciparum genome, which is 4 80% AT-rich and includes nonexonic intervals entirely devoid of C/G residues (Gardner et al. 2002), provides a challenge for CGH-based detection of CNV.”
BackgroundMethodInfluentialTargeting NAD+ Metabolism in the Human Malaria Parasite Plasmodium falciparum
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BackgroundPaired-end sequencing of Fosmid libraries by IlluminaPreprint
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“recalcitrant to cloning as Fosmids or BACs in the past (Gardner et al. 2002; Eichinger et al. 2005).”
BackgroundA New Single-Step PCR Assay for the Detection of the Zoonotic Malaria Parasite Plasmodium knowlesi
Lucchi, N., Poorak, M., Oberstaller, J., DeBarry, J., Srinivasamoorthy, G., Goldman, I., Xayavong, M. V., da Silva, A. D., Peterson, D., Barnwell, J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031848 · Cited by 57
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“This has led to a model in which translation is slowed down when the ribosome encounters long low-complexity Asn-repeat sequences due to the relatively lower concentrations of Asn:tRNA (Frugier et al. 2010; Filisetti et al. 2013).”
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“falciparum with 80% AT-rich is remarkably unusual and is recognized by the human immune system (28).”
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Kdetrees: Non-parametric Estimation of Phylogenetic Tree Distributions
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First-Trimester Plasmodium falciparum Infections Display a Typical “Placental” Phenotype
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“…trading as Taylor & Francis Group Journal of Biomolecular Structure and Dynamics, 2018 Vol. 36, No. 15, 3993–4009, https://doi.org/10.1080/07391102.2017.1404935 The genome sequencing of P. falciparum helps in the identification and selection of specific and new targets (Gardner et al., 2002).”
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Defining the biology component of the drug discovery strategy for malaria eradication
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MethodTurner, L., Lavstsen, T., Mmbando, B. P., Wang, C. W., Magistrado-Coxen, P., Vestergaard, L. S., Ishengoma, D. S., Minja, D. T. R., Lusingu, J., & Theander, T. G. (2015) · Infection and Immunity · doi:10.1128/iai.00271-15 · Cited by 59
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“falciparum genome is unique in certain features such as AT-rich content and nucleotide repeats [63].”
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The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite
Zhang, M., Wang, C.-Q. C. Q., Oberstaller, J., Thomas, P. J., Otto, T., Casandra, D., Boyapalle, S., Adapa, S. R., Xu, S., Button-Simons, K. A., et al. (2020) · Nature Communications · doi:10.1038/s41467-021-24814-1 · Cited by 49
“the wildtype parent NF54 via 109 RNAseq revealed concordance between (1) genes regulated in the parasite’s innate 110 response to HS, (2) the processes dysregulated in these mutants vs.”
BackgroundMethodInfluentialPeriodic Parasites and Daily Host Rhythms
Prior, K. F., Rijo‐Ferreira, F., de Assis, P. A., Hirako, I. C., Weaver, D. R., Gazzinelli, R. T., & Reece, S. E. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.01.005 · Cited by 67
Ebiloma, G. U., Balogun, E. O., Cueto-Diaz, E. J., de Koning, H. P., & Dardonville, C. Y. (2019) · Medicinal Research Reviews · doi:10.1002/med.21560 · Cited by 48
“The deposited structure qualifies for used in SADD. of AOXs.173,174 Indeed, the structure of TAO revealed the presence of two ferric ions positioned about 3.3 Å from each other and bridged together by one hydroxo group, which together with the coordinating amino acids (four glutamate residues Glu123, Glu162, Glu213, a…”
BackgroundInfluentialVaccine candidate discovery for the next generation of malaria vaccines
Tuju, J., Kamuyu, G., Murungi, L., & Osier, F. H. A. (2017) · Immunology · doi:10.1111/imm.12780 · Cited by 50
Singer, M., Marshall, J., Heiss, K., Mair, G., Grimm, D., Mueller, A., & Frischknecht, F. (2015) · Genome Biology · doi:10.1186/s13059-015-0811-1 · Cited by 49
“Genes involved in NHEJ have so far not been identified in any Plasmodium species [26, 27].”
BackgroundConstruction and validation of a detailed kinetic model of glycolysis in Plasmodium falciparum
Penkler, G. P., du Toit, F., Adams, W. W., Rautenbach, M., Palm, D. C., van Niekerk, D. D., & Snoep, J. L. (2015) · FEBS Journal · doi:10.1111/febs.13237 · Cited by 47
A genomic and evolutionary approach reveals non-genetic drug resistance in malaria
Herman, J. D., Rice, D. P., Ribacke, U., Silterra, J., Deik, A., Moss, E. L., Broadbent, K. M., Neafsey, D., Desai, M. M., Clish, C., et al. (2014) · Genome Biology · doi:10.1186/s13059-014-0511-2 · Cited by 49
“and roughly 5,500 expressed proteins in the parasites’ life cycles [11].”
BackgroundMonitoring parasite diversity for malaria elimination in sub-Saharan Africa
Ghansah, A., Amenga-Etego, L. N., Amambua-Ngwa, A., Andagalu, B., Apinjoh, T., Bouyou-Akotet, M., Cornelius, V., Golassa, L., Andrianaranjaka, V., Ishengoma, D., et al. (2014) · Science · doi:10.1126/science.1259423 · Cited by 49
Horizontal Gene Transfer is a Significant Driver of Gene Innovation in Dinoflagellates
Wisecaver, J. H., Brosnahan, M. L., & Hackett, J. D. (2013) · Genome Biology and Evolution · doi:10.1093/gbe/evt179 · Cited by 46
Biosynthesis of GDP-fucose and Other Sugar Nucleotides in the Blood Stages of Plasmodium falciparum
Sanz, S., Bandini, G., Ospina, D. A., Bernabeu, M., Mariño, K. V., Fernández-Becerra, C., & Izquierdo, L. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.439828 · Cited by 42
The adjacent positioning of co-regulated gene pairs is widely conserved across eukaryotes
Arnone, J. T., Robbins‐Pianka, A., Arace, J. R., Kass-Gergi, S., & McAlear, M. A. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-546 · Cited by 52
“falciparum [56], G.”
Asghar, M., Westerdahl, H., Zehtindjiev, P., Ilieva, M., Hasselquist, D., & Bensch, S. (2012) · Parasitology · doi:10.1017/s0031182012000510 · Cited by 49
Ikerionwu, C., Ugwuishiwu, C. H., Okpala, I., James, I., Okoronkwo, M. C., Nnadi, C. O., Orji, U. E., Ebem, D. U., & Ike, A. C. (2022) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2022.103198 · Cited by 56
Salomaki, E. D., Terpis, K. X., Rueckert, S., Kotyk, M., Varadínová, Z. K., Čepička, I., Lane, C. E., & Kolísko, M. (2021) · BMC Biology · doi:10.1186/s12915-021-01007-2 · Cited by 65
“Due to public health implications, medically important apicomplexans were an early focus for genome sequencing efforts and remain as some of the most well-studied microbial eukaryotes [1, 2, 4].”
BackgroundGenome Evolution of Coral Reef Symbionts as Intracellular Residents.
González-Pech, R. A., Bhattacharya, D., Ragan, M., & Chan, C. (2019) · Trends in Ecology & Evolution · doi:10.1016/j.tree.2019.04.010 · Cited by 48
CRISPR in Parasitology: Not Exactly Cut and Dried!
Bryant, J. M., Baumgarten, S., Glover, L., Hutchinson, S., & Rachidi, N. (2019) · Trends in Parasitology · doi:10.1016/j.pt.2019.03.004 · Cited by 58
Characterization of the accessible genome in the human malaria parasite Plasmodium falciparum
Ruiz, J. L., Tena, J. J., Bancells, C., Cortés, A., Gómez-Skármeta, J. L., & Gómez‐Díaz, E. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky643 · Cited by 77
InsP3 Signaling in Apicomplexan Parasites
Garcia, C. R. S., Alves, E., Pereira, P. H. S., Bartlett, P. J., Thomas, A. P., Mikoshiba, K., Plattner, H., & Sibley, L. (2017) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026617666170130121042 · Cited by 48
“In Plasmodium, Gardner et al., 2002 [17] reported a gene encoding the enzyme phosphatidylinositol 4-kinase (PI4K) that catalyses the formation of phosphatidylinositol 4-phosphate (PIP) from phosphatidylinositol (PI).”
BackgroundInfluentialPasini, E., Böhme, U., Rutledge, G. G., der Wel, A. M. V.-V., Sanders, M., Berriman, M., Kocken, C., & Otto, T. (2017) · Wellcome Open Research · doi:10.12688/wellcomeopenres.11864.1 · Cited by 48
Self-citationDevelopment of High Resolution Melting Analysis for the Diagnosis of Human Malaria
Chua, K. H., Lim, S. C., Ng, C. C., Lee, P. C., Lim, Y. A. L., Lau, T. P., & Chai, H. C. (2015) · Scientific Reports · doi:10.1038/srep15671 · Cited by 54
Paths to a malaria vaccine illuminated by parasite genomics
Conway, D. (2015) · Trends in Genetics · doi:10.1016/j.tig.2014.12.005 · Cited by 48
Genome-based vaccine design: the promise for malaria and other infectious diseases
Doolan, D. L., Apte, S. H., & Proietti, C. (2014) · International Journal for Parasitology · doi:10.1016/j.ijpara.2014.07.010 · Cited by 47
Nuclear Glycolytic Enzyme Enolase of Toxoplasma gondii Functions as a Transcriptional Regulator
Mouveaux, T., Oria, G., Werkmeister, E., Slomianny, C., Fox, B., Bzik, D., & Tomavo, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0105820 · Cited by 48
A new computational approach redefines the subtelomeric vir superfamily of Plasmodium vivax
Lopez, F. J., Bernabeu, M., Fernández-Becerra, C., & Portillo, H. A. D. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-8 · Cited by 43
“In order to validate this clustering approach, we tested this algorithm using protein sequences from the RIFIN/STEVOR, Pfmc-2TM, fEMP1 and SURFIN subtelomeric multigene families of P. falciparum [19].”
MethodEffects of Antimalarial Molecules on the Gametocyte Stage of Plasmodium falciparum: The Debate
Dechy‐Cabaret, O., & Benoit‐Vical, F. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3005898 · Cited by 42
Genome cartography: charting the apicomplexan genome
Kissinger, J. C., & DeBarry, J. D. (2011) · Trends in Parasitology · doi:10.1016/j.pt.2011.03.006 · Cited by 51
“falciparum which encode the erythrocyte membrane protein, PfEMP1 [5, 6, 9].”
InfluentialStorm, J., Perner, J., Aparicio, I. M., Patzewitz, E.-M., Olszewski, K. L., Llinás, M., Engel, P., & Müller, S. (2011) · Malaria Journal · doi:10.1186/1475-2875-10-193 · Cited by 48
“falciparum contains three genes encoding potential glutamate dehydrogenases; two are NADP(H)-dependent proteins while the cofactor specificity of the third has not been determined to date [2,3].”
InfluentialPlasmodium vivax Malaria Viewed through the Lens of an Eradicated European Strain
van Dorp, L., Gelabert, P., Rieux, A., de Manuel, M., de-Dios, T., Gopalakrishnan, S., Carøe, C., Sandoval‐Velasco, M., Fregel, R., Olalde, Í., et al. (2019) · Molecular Biology and Evolution · doi:10.1093/molbev/msz264 · Cited by 53
“To increase the final coverage, all Plasmodium reads were pooled and an in-house script was used to discriminate reads mapping more confidently to the P. vivax (PvP01) (Auburn et al. 2016) compared to the P. falciparum 3D7 (Gardner et al. 2002) reference genomes based on edit distance.”
MethodCauses and Effects of Loss of Classical Nonhomologous End Joining Pathway in Parasitic Eukaryotes
Nenarokova, A., Záhonová, K., Krasiļņikova, M., Gahura, O., McCulloch, R., Zı́ková, A., Yurchenko, V., & Lukeš, J. (2019) · mBio · doi:10.1128/mbio.01541-19 · Cited by 48
RNA Polymerase III as a Gatekeeper to Prevent Severe VZV Infections
Carter-Timofte, M. E., Paludan, S. R., & Mogensen, T. H. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.07.009 · Cited by 49
Kanyal, A., Rawat, M., Gurung, P., Choubey, D., Anamika, K., & Karmodiya, K. (2017) · FEBS Journal · doi:10.1111/febs.14376 · Cited by 57
Roy, K. K. (2017) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2017.04.006 · Cited by 47
Ngwa, C. J., Kiesow, M. J., Papst, O., Orchard, L. M., Filarsky, M., Rosinski, A. N., Voss, T., Llinás, M., & Pradel, G. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00320 · Cited by 47
“…five plasmodial HDACs; i.e., PfHDAC1 and 3, PfHda2 and the two type III silent information regulators PfSir2A and PfSir2B (Joshi et al., 1999; Gardner et al., 2002; reviewed in Cui and Miao, 2010) and four HATs, including the previously reported MYST and PfGNC5 (Cui et al., 2007a; Miao et…”
BackgroundZininga, T., Achilonu, I., Hoppe, H., Prinsloo, E., Dirr, H., & Shonhai, A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129445 · Cited by 47
Heitlinger, E., Spork, S., Lucius, R., & Dieterich, C. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-696 · Cited by 47
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Freimanis, G., Sedegah, M., Owusu-Ofori, S., Kumar, S., & Allain, J. (2013) · Transfusion · doi:10.1111/j.1537-2995.2012.03943.x · Cited by 47
Kishore, S. P., Stiller, J. W., & Deitsch, K. (2013) · BMC Evolutionary Biology · doi:10.1186/1471-2148-13-37 · Cited by 45
“In the case of the Apicomplexa, therefore, two major potential sources for HGT have been established: i) transfer from an algal endosymbiont (fatty acid synthases or ApiAP2 transcription factors) [3,8], or ii) transfer from an animal host (domains involved in cytoadhesion and O-linked glycosylation) [6,7].”
BackgroundComparative genome analysis of six malarial parasites using codon usage bias based tools
Yadav, M., & Swati, D. (2012) · Bioinformation · doi:10.6026/97320630081230 · Cited by 47
Tonelli, R. R., Colli, W., & Alves, M. (2012) · Front. Immun. · doi:10.3389/fimmu.2012.00419 · Cited by 47
“This variation is mediated by the differential control of a family of surface molecules termed PfEMP1 and encoded by approximately 60 var genes as described by the genome sequencing of P. falciparum (Aley et al., 1984; Gardner et al., 2002).”
BackgroundSumner, K. M., Freedman, E., Abel, L., Obala, A. A., Pence, B. W., Wesolowski, A., Meshnick, S. R., Prudhomme-O’Meara, W., & Taylor, S. M. (2021) · Nature Communications · doi:10.1038/s41467-021-21269-2 · Cited by 56
tRNA epitranscriptomics and biased codon are linked to proteome expression in Plasmodium falciparum
Ng, C., Sinha, A., Aniweh, Y., Nah, Q., Babu, I. R., Gu, C., Chionh, Y., Dedon, P., & Preiser, P. (2018) · Molecular Systems Biology · doi:10.15252/msb.20178009 · Cited by 46
“…has a complete set of eukaryotic RNA species with no evidence of miRNA, while the organelle apicoplast contains rRNA of plastid and bacterial origin (Waters et al , 1989, 1995; Gardner et al , 1993, 2002; Li et al , 1994; John Rogers et al , 1996; Hughes et al , 2010; Jackson et al , 2011).”
InfluentialPallarès, I., de Groot, N. S., Iglesias, V., Sant’Anna, R., Biosca, A., Fernàndez‐Busquets, X., & Ventura, S. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01737 · Cited by 55
“It is worth to mention that this analysis is constrained by the fact that 60% of P. falciparum genes have unknown functions (Gardner et al., 2002), most of them have no clear homolog in other eukaryotes, and that the mechanisms underlying the main processes related to malaria pathogenesis in P.…”
BackgroundInfluentialPlasmodium vivax Biology: Insights Provided by Genomics, Transcriptomics and Proteomics
Bourgard, C., Albrecht, L., Kayano, A. C. A. V., Sunnerhagen, P., & Costa, F. T. M. (2018) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2018.00034 · Cited by 50
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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