Genome sequence of the human malaria parasite Plasmodium falciparum

Breman, J. G. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am. J. Trop. Med. Hyg. 64, 1–11 (2001)

Greenwood, B. & Mutabingwa, T. Malaria in 2002. Nature 415, 670–672 (2002)

Gallup, J. L. & Sachs, J. D. The economic burden of malaria. Am. J. Trop. Med. Hyg. 64, 85–96 (2001)

Hoffman, S. L. et al. Funding for malaria genome sequencing. Nature 387, 647 (1997)

Gardner, M. J. et al. Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science 282, 1126–1132 (1998)

Bowman, S. et al. The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature 400, 532–538 (1999)

Hall, N. et al. Sequence of Plasmodium falciparum chromosomes 1, 3–9 and 13. Nature 419, 527–531 (2002)

Gardner, M. J. et al. Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14. Nature 419, 531–534 (2002)

Hyman, R. W. et al. Sequence of Plasmodium falciparum chromosome 12. Nature 419, 534–537 (2002)

Foster, J. & Thompson, J. The Plasmodium falciparum genome project: a resource for researchers. Parasitol. Today 11, 1–4 (1995)

Su, X. et al. A genetic map and recombination parameters of the human malaria parasite Plasmodium falciparum. Science 286, 1351–1353 (1999)

Su, X. Z. & Wellems, T. E. Toward a high-resolution Plasmodium falciparum linkage map: polymorphic markers from hundreds of simple sequence repeats. Genomics 33, 430–444 (1996)

Lai, Z. et al. A shotgun optical map of the entire Plasmodium falciparum genome. Nature Genet. 23, 309–313 (1999)

Florens, L. et al. A proteomic view of the Plasmodium falciparum life cycle. Nature 419, 520–526 (2002)

Lasonder, E. et al. Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry. Nature 419, 537–542 (2002)

Watanabe, J., Sasaki, M., Suzuki, Y. & Sugano, S. FULL-malaria: a database for a full-length enriched cDNA library from human malaria parasite, Plasmodium falciparum. Nucleic Acids Res. 29, 70–71 (2001)

Gamain, B. et al. Increase in glutathione peroxidase activity in malaria parasite after selenium supplementation. Free Radic. Biol. Med. 21, 559–565 (1996)

Katinka, M. D. et al. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414, 450–453 (2001)

Moriyama, E. N. & Powell, J. R. Codon usage bias and tRNA abundance in Drosophila. J. Mol. Evol. 45, 514–523 (1997)

Duret, L. tRNA gene number and codon usage in the C. elegans genome are co-adapted for optimal translation of highly expressed genes. Trends Genet. 16, 287–289 (2000)

Vaidya, A. B., Akella, R. & Suplick, K. Sequences similar to genes for two mitochondrial proteins and portions of ribosomal RNA in tandemly arrayed 6-kilobase-pair DNA of a malaria parasite. Mol. Biochem. Parasitol. 35, 97–107 (1989)

Vaidya, A. B., Lashgari, M. S., Pologe, L. G. & Morrisey, J. Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones. Mol. Biochem. Parasitol. 58, 33–42 (1993)

Tan, T. H., Pach, R., Crausaz, A., Ivens, A. & Schneider, A. tRNAs in Trypanosoma brucei: genomic organization, expression, and mitochondrial import. Mol. Cell. Biol. 22, 3707–3717 (2002)

Tarassov, I. A. & Martin, R. P. Mechanisms of tRNA import into yeast mitochondria: an overview. Biochimie 78, 502–510 (1996)

Wilson, R. J. M. et al. Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum. J. Mol. Biol. 261, 155–172 (1996)

Li, J., Wirtz, R. A., McConkey, G. A., Sattabongkot, J. & McCutchan, T. F. Transition of Plasmodium vivax ribosome types corresponds to sporozoite differentiation in the mosquito. Mol. Biochem. Parasitol. 65, 283–289 (1994)

Waters, A. P. The ribosomal RNA genes of Plasmodium. Adv. Parasitol. 34, 33–79 (1994)

Babiker, H. A., Creasey, A. M., Bayoumi, R. A., Walliker, D. & Arnot, D. E. Genetic diversity of Plasmodium falciparum in a village in eastern Sudan. 2. Drug resistance, molecular karyotypes and the mdr1 genotype of recent isolates. Trans. R. Soc. Trop. Med. Hyg. 85, 578–583 (1991)

Hinterberg, K., Mattei, D., Wellems, T. E. & Scherf, A. Interchromosomal exchange of a large subtelomeric segment in a Plasmodium falciparum cross. EMBO J. 13, 4174–4180 (1994)

Hernandez, R. R., Hinterberg, K. & Scherf, A. Compartmentalization of genes coding for immunodominant antigens to fragile chromosome ends leads to dispersed subtelomeric gene families and rapid gene evolution in Plasmodium falciparum. Mol. Biochem. Parasitol. 78, 137–148 (1996)

Scherf, A. et al. Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametocytogenesis. EMBO J. 11, 2293–2301 (1992)

Day, K. P. et al. Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0.3-megabase region of chromosome 9. Proc. Natl Acad. Sci. USA 90, 8292–8296 (1993)

Pologe, L. G. & Ravetch, J. V. A chromosomal rearrangement in a P. falciparum histidine-rich protein gene is associated with the knobless phenotype. Nature 322, 474–477 (1986)

Louis, E. J., Naumova, E. S., Lee, A., Naumov, G. & Haber, J. E. The chromosome end in yeast: its mosaic nature and influence on recombinational dynamics. Genetics 136, 789–802 (1994)

van Deutekom, J. C. et al. Evidence for subtelomeric exchange of 3.3 kb tandemly repeated units between chromosomes 4q35 and 10q26: implications for genetic counselling and etiology of FSHD1. Hum. Mol. Genet. 5, 1997–2003 (1996)

Rudenko, G., McCulloch, R., Dirks-Mulder, A. & Borst, P. Telomere exchange can be an important mechanism of variant surface glycoprotein gene switching in Trypanosoma brucei. Mol. Biochem. Parasitol. 80, 65–75 (1996)

Figueiredo, L. M., Freitas-Junior, L. H., Bottius, E., Olivo-Marin, J. C. & Scherf, A. A central role for Plasmodium falciparum subtelomeric regions in spatial positioning and telomere length regulation. EMBO J. 21, 815–824 (2002)

Scherf, A., Figueiredo, L. M. & Freitas-Junior, L. H. Plasmodium telomeres: a pathogen's perspective. Curr. Opin. Microbiol. 4, 409–414 (2001)

Vernick, K. D. & McCutchan, T. F. Sequence and structure of a Plasmodium falciparum telomere. Mol. Biochem. Parasitol. 28, 85–94 (1988)

Oquendo, P. et al. Characterisation of a repetitive DNA sequence from the malaria parasite, Plasmodium falciparum. Mol. Biochem. Parasitol. 18, 89–101 (1986)

De Bruin, D., Lanzer, M. & Ravetch, J. V. The polymorphic subtelomeric regions of Plasmodium falciparum chromosomes contain arrays of repetitive sequence elements. Proc. Natl Acad. Sci. USA 91, 619–623 (1994)

Ashburner, M. et al. Gene ontology: tool for the unification of biology. Nature Genet. 25, 25–29 (2000)

McFadden, G. I., Reith, M., Munhollan, J. & Lang-Unnasch, N. Plastid in human parasites. Nature 381, 482–483 (1996)

Kohler, S. et al. A plastid of probable green algal origin in apicomplexan parasites. Science 275, 1485–1489 (1997)

Fichera, M. E. & Roos, D. S. A plastid organelle as a drug target in apicomplexan parasites. Nature 390, 407–409 (1997)

He, C. Y., Striepen, B., Pletcher, C. H., Murray, J. M. & Roos, D. S. Targeting and processing of nuclear-encoded apicoplast proteins in plastid segregation mutants of Toxoplasma gondii. J. Biol. Chem. 276, 28436–28442 (2001)

Waller, R. F. et al. Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proc. Natl Acad. Sci. USA 95, 12352–12357 (1998)

Surolia, N. & Surolia, A. Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nature Med. 7, 167–173 (2001)

Jomaa, H. et al. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285, 1573–1576 (1999)

Sato, S. & Wilson, R. J. The genome of Plasmodium falciparum encodes an active delta-aminolevulinic acid dehydratase. Curr. Genet. 40, 391–398 (2002)

Van Dooren, G. G., Su, V., D'Ombrain, M. C. & McFadden, G. I. Processing of an apicoplast leader sequence in Plasmodium falciparum and the identification of a putative leader cleavage enzyme. J. Biol. Chem. 277, 23612–23619 (2002)

Wilson, R. J. Progress with parasite plastids. J. Mol. Biol. 319, 257–274 (2002)

Stoebe, B. & Kowallik, K. V. Gene-cluster analysis in chloroplast genomics. Trends Genet. 15, 344–347 (1999)

Fast, N. M., Kissinger, J. C., Roos, D. S. & Keeling, P. J. Nuclear-encoded, plastid-targeted genes suggest a single common origin for apicomplexan and dinoflagellate plastids. Mol. Biol. Evol 18, 418–426 (2001)

Roos, D. S. et al. Origin, targeting, and function of the apicomplexan plastid. Curr. Opin. Microbiol. 2, 426–432 (1999)

Palmer, J. D. & Delwiche, C. F. Second-hand chloroplasts and the case of the disappearing nucleus. Proc. Natl Acad. Sci. USA 93, 7432–7435 (1996)

Waller, R. F., Reed, M. B., Cowman, A. F. & McFadden, G. I. Protein trafficking to the plastid of Plasmodium falciparum is via the secretory pathway. EMBO J. 19, 1794–1802 (2000)

DeRocher, A., Hagen, C. B., Froehlich, J. E., Feagin, J. E. & Parsons, M. Analysis of targeting sequences demonstrates that trafficking to the Toxoplasma gondii plastid branches off the secretory system. J. Cell Sci. 113 (Part 22), 3969–3977 (2000)

van Dooren, G. G., Schwartzbach, S. D., Osafune, T. & McFadden, G. I. Translocation of proteins across the multiple membranes of complex plastids. Biochim. Biophys. Acta 1541, 34–53 (2001)

Yung, S., Unnasch, T. R. & Lang-Unnasch, N. Analysis of apicoplast targeting and transit peptide processing in Toxoplasma gondii by deletional and insertional mutagenesis. Mol. Biochem. Parasitol. 118, 11–21 (2001)

Zuegge, J., Ralph, S., Schmuker, M., McFadden, G. I. & Schneider, G. Deciphering apicoplast targeting signals—feature extraction from nuclear-encoded precursors of Plasmodium falciparum apicoplast proteins. Gene 280, 19–26 (2001)

Vollmer, M., Thomsen, N., Wiek, S. & Seeber, F. Apicomplexan parasites possess distinct nuclear-encoded, but apicoplast-localized, plant-type ferredoxin-NADP+ reductase and ferredoxin. J. Biol. Chem. 276, 5483–5490 (2001)

Ralph, S. A., D'Ombrain, M. C. & McFadden, G. I. The apicoplast as an antimalarial drug target. Drug Resist. Updat. 4, 145–151 (2001)

Baldauf, S. L., Roger, A. J., Wenk-Siefert, I. & Doolittle, W. F. A kingdom-level phylogeny of eukaryotes based on combined protein data. Science 290, 972–977 (2000)

Wood, V. et al. The genome sequence of Schizosaccharomyces pombe. Nature 415, 871–880 (2002)

Eisen, J. A. Phylogenomics: improving functional predictions for uncharacterized genes by evolutionary analysis. Genome Res. 8, 163–167 (1998)

Adams, K. L., Daley, D. O., Whelan, J. & Palmer, J. D. Genes for two mitochondrial ribosomal proteins in flowering plants are derived from their chloroplast or cytosolic counterparts. Plant Cell 14, 931–943 (2002)

Kanehisa, M., Goto, S., Kawashima, S. & Nakaya, A. The KEGG databases at GenomeNet. Nucleic Acids Res. 30, 42–46 (2002)

Sherman, I. W. in Malaria Parasite Biology, Pathogenesis, and Protection (ed. Sherman, I. W.) 135–143 (ASM, Washington DC, 1998)

Buckwitz, D., Jacobasch, G., Gerth, C., Holzhutter, H. G. & Thamm, R. A kinetic model of phosphofructokinase from Plasmodium berghei. Influence of ATP and fructose-6-phosphate. Mol. Biochem. Parasitol. 27, 225–232 (1988)

Buckwitz, D., Jacobasch, G. & Gerth, C. Phosphofructokinase from Plasmodium berghei. Influence of Mg2+, ATP and Mg2+-complexed ATP. Biochem. J. 267, 353–357 (1990)

Clarke, J. L., Scopes, D. A., Sodeinde, O. & Mason, P. J. Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase. A novel bifunctional enzyme in malaria parasites. Eur. J. Biochem. 268, 2013–2019 (2001)

Miclet, E. et al. NMR spectroscopic analysis of the first two steps of the pentose-phosphate pathway elucidates the role of 6-phosphogluconolactonase. J. Biol. Chem. 276, 34840–34846 (2001)

Loyevsky, M. et al. An IRP-like protein from Plasmodium falciparum binds to a mammalian iron-responsive element. Blood 98, 2555–2562 (2001)

Lang-Unnasch, N. Purification and properties of Plasmodium falciparum malate dehydrogenase. Mol. Biochem. Parasitol. 50, 17–25 (1992)

Blum, J. J. & Ginsburg, H. Absence of α-ketoglutarate dehydrogenase activity and presence of CO2-fixing activity in Plasmodium falciparum grown in vitro in human erythrocytes. J. Protozool. 31, 167–169 (1984)

Fry, M. & Beesley, J. E. Mitochondria of mammalian Plasmodium spp. Parasitology 102, 17–26 (1991)

Vaidya, A. B. in Malaria: Parasite Biology, Pathogenesis, and Protection (ed. Sherman, I. W.) 355–368 (ASM, Washington DC, 1998)

Papa, S., Zanotti, F. & Gaballo, A. The structural and functional connection between the catalytic and proton translocating sectors of the mitochondrial F1F0-ATP synthase. J. Bioenerg. Biomembr. 32, 401–411 (2000)

Sherman, I. W. in Malaria: Parasite Biology, Pathogenesis, and Protection (ed. Sherman, I. W.) 177–184 (ASM, Washington DC, 1998)

de Macedo, C. S., Uhrig, M. L., Kimura, E. A. & Katzin, A. M. Characterization of the isoprenoid chain of coenzyme Q in Plasmodium falciparum. FEMS Microbiol. Lett. 207, 13–20 (2002)

Trumpower, B. L. & Gennis, R. B. Energy transduction by cytochrome complexes in mitochondrial and bacterial respiration: the enzymology of coupling electron transfer reactions to transmembrane proton translocation. Annu. Rev. Biochem. 63, 675–716 (1994)

Vaidya, A. B., McIntosh, M. T. & Srivastava, I. K. Membrane Structure in Disease and Drug Therapy (ed. Zimmer, G.) (Marcel Dekker, New York, 2000)

Perez-Martinez, X. et al. Subunit II of cytochrome c oxidase in Chlamydomonad algae is a heterodimer encoded by two independent nuclear genes. J. Biol. Chem. 276, 11302–11309 (2001)

Murphy, A. D. & Lang-Unnasch, N. Alternative oxidase inhibitors potentiate the activity of atovaquone against Plasmodium falciparum. Antimicrob. Agents Chemother. 43, 651–654 (1999)

Dieckmann, A. & Jung, A. Mechanisms of sulfadoxine resistance in Plasmodium falciparum. Mol. Biochem. Parasitol. 19, 143–147 (1986)

McConkey, G. A. Targeting the shikimate pathway in the malaria parasite Plasmodium falciparum. Antimicrob. Agents Chemother. 43, 175–177 (1999)

Roberts, F. et al. Evidence for the shikimate pathway in apicomplexan parasites. Nature 393, 801–805 (1998)

Roberts, C. W. et al. The shikimate pathway and its branches in apicomplexan parasites. J. Infect. Dis. 185 (Suppl. 1), S25–S36 (2002)

Keeling, P. J. et al. Shikimate pathway in apicomplexan parasites. Nature 397, 219–220 (1999)

Fitzpatrick, T. et al. Subcellular localization and characterization of chorismate synthase in the apicomplexan Plasmodium falciparum. Mol. Microbiol. 40, 65–75 (2001)

Duncan, K., Edwards, R. M. & Coggins, J. R. The pentafunctional arom enzyme of Saccharomyces cerevisiae is a mosaic of monofunctional domains. Biochem. J. 246, 375–386 (1987)

Rubin, H. et al. Cloning, sequence determination, and regulation of the ribonucleotide reductase subunits from Plasmodium falciparum: a target for antimalarial therapy. Proc. Natl Acad. Sci. USA 90, 9280–9284 (1993)

Chakrabarti, D., Schuster, S. M. & Chakrabarti, R. Cloning and characterization of subunit genes of ribonucleotide reductase, a cell-cycle-regulated enzyme, from Plasmodium falciparum. Proc. Natl Acad. Sci. USA 90, 12020–12024 (1993)

Krnajski, Z., Gilberger, T. W., Walter, R. D. & Muller, S. The malaria parasite Plasmodium falciparum possesses a functional thioredoxin system. Mol. Biochem. Parasitol. 112, 219–228 (2001)

Bonday, Z. Q., Dhanasekaran, S., Rangarajan, P. N. & Padmanaban, G. Import of host δ-aminolevulinate dehydratase into the malarial parasite: identification of a new drug target. Nature Med. 6, 898–903 (2000)

Bonday, Z. Q., Taketani, S., Gupta, P. D. & Padmanaban, G. Heme biosynthesis by the malarial parasite. Import of δ-aminolevulinate dehydrase from the host red cell. J. Biol. Chem. 272, 21839–21846 (1997)

Wilson, C. M., Smith, A. B. & Baylon, R. V. Characterization of the δ-aminolevulinate synthase gene homologue in P. falciparum. Mol. Biochem. Parasitol. 75, 271–276 (1996)

Sato, S., Tews, I. & Wilson, R. J. Impact of a plastid-bearing endocytobiont on apicomplexan genomes. Int. J. Parasitol. 30, 427–439 (2000)

Rohdich, F. et al. Biosynthesis of terpenoids. 2C-Methyl-D-erythritol 2,4-cyclodiphosphate synthase (IspF) from Plasmodium falciparum. Eur. J. Biochem. 268, 3190–3197 (2001)

Kemp, L. E., Bond, C. S. & Hunter, W. N. Structure of 2C-methyl-D-erythritol 2,4- cyclodiphosphate synthase: an essential enzyme for isoprenoid biosynthesis and target for antimicrobial drug development. Proc. Natl Acad. Sci. USA 99, 6591–6596 (2002)

Paulsen, I. T., Nguyen, L., Sliwinski, M. K., Rabus, R. & Saier, M. H. Jr Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes. J. Mol. Biol. 301, 75–100 (2000)

Woodrow, C. J., Burchmore, R. J. & Krishna, S. Hexose permeation pathways in Plasmodium falciparum-infected erythrocytes. Proc. Natl Acad. Sci. USA 97, 9931–9936 (2000)

Hansen, M., Kun, J. F., Schultz, J. E. & Beitz, E. A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites. J. Biol. Chem. 277, 4874–4882 (2002)

Elliott, J. L., Saliba, K. J. & Kirk, K. Transport of lactate and pyruvate in the intraerythrocytic malaria parasite, Plasmodium falciparum. Biochem. J. 355, 733–739 (2001)

Rager, N., Mamoun, C. B., Carter, N. S., Goldberg, D. E. & Ullman, B. Localization of the Plasmodium falciparum PfNT1 nucleoside transporter to the parasite plasma membrane. J. Biol. Chem. 276, 41095–41099 (2001)

Dyer, M., Wong, I. H., Jackson, M., Huynh, P. & Mikkelsen, R. Isolation and sequence analysis of a cDNA encoding an adenine nucleotide translocator from Plasmodium falciparum. Biochim. Biophys. Acta 1186, 133–136 (1994)

McIntosh, M. T., Drozdowicz, Y. M., Laroiya, K., Rea, P. A. & Vaidya, A. B. Two classes of plant-like vacuolar-type H+-pyrophosphatases in malaria parasites. Mol. Biochem. Parasitol. 114, 183–195 (2001)

Fidock, A. D. et al. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol. Cell 6, 861–871 (2000)

Desai, S. A., Bezrukov, S. M. & Zimmerberg, J. A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature 406, 1001–1005 (2000)

Eisen, J. A. & Hanawalt, P. C. A phylogenomic study of DNA repair genes, proteins, and processes. Mutat. Res. 435, 171–213 (1999)

Wood, R. D., Mitchell, M., Sgouros, J. & Lindahl, T. Human DNA repair genes. Science 291, 1284–1289 (2001)

Haltiwanger, B. M. et al. DNA base excision repair in human malaria parasites is predominantly by a long-patch pathway. Biochemistry 39, 763–772 (2000)

Critchlow, S. E. & Jackson, S. P. DNA end-joining: from yeast to man. Trends Biochem. Sci. 23, 394–398 (1998)

Freitas-Junior, L. H. et al. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407, 1018–1022 (2000)

Bannister, L. H., Hopkins, J. M., Fowler, R. E., Krishna, S. & Mitchell, G. H. A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages. Parasitol. Today 16, 427–433 (2000)

van Dooren, G. G., Waller, R. F., Joiner, K. A., Roos, D. S. & McFadden, G. I. Traffic jams: protein transport in Plasmodium falciparum. Parasitol. Today 16, 421–427 (2000)

Wiser, M. F., Lanners, H. N., Bafford, R. A. & Favaloro, J. M. A novel alternate secretory pathway for the export of Plasmodium proteins into the host erythrocyte. Proc. Natl Acad. Sci. USA 94, 9108–9113 (1997)

Albano, F. R. et al. A homologue of Sar1p localises to a novel trafficking pathway in malaria-infected erythrocytes. Eur. J. Cell Biol. 78, 453–462 (1999)

Adisa, A., Albano, F. R., Reeder, J., Foley, M. & Tilley, L. Evidence for a role for a Plasmodium falciparum homologue of Sec31p in the export of proteins to the surface of malaria parasite-infected erythrocytes. J. Cell Sci. 114, 3377–3386 (2001)

Hayashi, M. et al. A homologue of N-ethylmaleimide-sensitive factor in the malaria parasite Plasmodium falciparum is exported and localized in vesicular structures in the cytoplasm of infected erythrocytes in the brefeldin A-sensitive pathway. J. Biol. Chem. 276, 15249–15255 (2001)

Knapp, B., Hundt, E. & Kupper, H. A. A new blood stage antigen of Plasmodium falciparum transported to the erythrocyte surface. Mol. Biochem. Parasitol. 37, 47–56 (1989)

Sacher, M. et al. TRAPP, a highly conserved novel complex on the cis-Golgi that mediates vesicle docking and fusion. EMBO J. 17, 2494–2503 (1998)

Leech, J. H., Barnwell, J. W., Miller, L. H. & Howard, R. J. Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes. J. Exp. Med. 159, 1567–1575 (1984)

Weber, J. L. Interspersed repetitive DNA from Plasmodium falciparum. Mol. Biochem. Parasitol. 29, 117–124 (1988)

Su, Z. et al. The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell 82, 89–100 (1995)

Baruch, D. I. et al. Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell 82, 77–87 (1995)

Smith, J. D. et al. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell 82, 101–110 (1995)

Cheng, Q. et al. stevor and rif are Plasmodium falciparum multicopy gene families which potentially encode variant antigens. Mol. Biochem. Parasitol. 97, 161–176 (1998)

Kyes, S. A., Rowe, J. A., Kriek, N. & Newbold, C. I. Rifins: A second family of clonally variant proteins expressed on the surface of red cells infected with Plasmodium falciparum. Proc. Natl Acad. Sci. USA 96, 9333–9338 (1999)

Kyes, S., Horrocks, P. & Newbold, C. Antigenic variation at the infected red cell surface in malaria. Annu. Rev. Microbiol. 55, 673–707 (2001)

Urban, B. C. et al. Plasmodium falciparum-infected erythrocytes modulate the maturation of dendritic cells. Nature 400, 73–77 (1999)

Pain, A. et al. Platelet-mediated clumping of Plasmodium falciparum-infected erythrocytes is a common adhesive phenotype and is associated with severe malaria. Proc. Natl Acad. Sci. USA 98, 1805–1810 (2001)

Fried, M. & Duffy, P. E. Adherence of Plasmodium falciparum to chondroitin sulfate A in the human placenta. Science 272, 1502–1504 (1996)

Udomsangpetch, R. et al. Plasmodium falciparum-infected erythrocytes form spontaneous erythrocyte rosettes. J. Exp. Med. 169, 1835–1840 (1989)

Bull, P. C. et al. Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nature Med. 4, 358–360 (1998)

Peterson, D. S., Miller, L. H. & Wellems, T. E. Isolation of multiple sequences from the Plasmodium falciparum genome that encode conserved domains homologous to those in erythrocyte binding proteins. Proc. Natl Acad. Sci. USA 92, 7100–7104 (1995)

Baruch, D. I. et al. Identification of a region of PfEMP1 that mediates adherence of Plasmodium falciparum infected erythrocytes to CD36: conserved function with variant sequence. Blood 90, 3766–3775 (1997)

Smith, J. D., Gamain, B., Baruch, D. I. & Kyes, S. Decoding the language of var genes and Plasmodium falciparum sequestration. Trends Parasitol. 17, 538–545 (2001)

Smith, J. D. et al. Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proc. Natl Acad. Sci. USA 97, 1766–1771 (2000)

Voss, T. S. et al. Genomic distribution and functional characterisation of two distinct and conserved Plasmodium falciparum var gene 5′ flanking sequences. Mol. Biochem. Parasitol. 107, 103–115 (2000)

Deitsch, K. W., Calderwood, M. S. & Wellems, T. E. Malaria. Cooperative silencing elements in var genes. Nature 412, 875–876 (2001)

Rowe, J. A., Kyes, S. A., Rogerson, S. J., Babiker, H. A. & Raza, A. Identification of a conserved Plasmodium falciparum var gene implicated in malaria in pregnancy. J. Infect. Dis. 185, 1207–1211 (2002)

Lue, H., Kleemann, R., Calandra, T., Roger, T. & Bernhagen, J. Macrophage migration inhibitory factor (MIF): mechanisms of action and role in disease. Microbes Infect. 4, 449–460 (2002)

Pastrana, D. V. et al. Filarial nematode parasites secrete a homologue of the human cytokine macrophage migration inhibitory factor. Infect. Immun. 66, 5955–5963 (1998)

Richie, T. L. & Saul, A. Progress and challenges for malaria vaccines. Nature 415, 694–701 (2002)

Bojang, K. A. et al. Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial. Lancet 358, 1927–1934 (2001)

Kapp, C. Global fund on AIDS, tuberculosis, and malaria holds first board meeting. Lancet 359, 414 (2002)

Nchinda, T. C. Malaria: a reemerging disease in Africa. Emerg. Infect. Dis. 4, 398–403 (1998)

Ridley, R. G. Medical need, scientific opportunity and the drive for antimalarial drugs. Nature 415, 686–693 (2002)

Nabarro, D. N. & Tayler, E. M. The “roll back malaria” campaign. Science 280, 2067–2068 (1998)

Delcher, A. L., Phillippy, A., Carlton, J. & Salzberg, S. L. Fast algorithms for large-scale genome alignment and comparison. Nucleic Acids Res. 30, 2478–2483 (2002)

Benson, G. Tandem repeats finder: a program to analyse DNA sequences. Nucleic Acids Res. 27, 573–580 (1999)

Pearson, W. R. Flexible sequence similarity searching with the FASTA3 program package. Methods Mol. Biol. 132, 185–219 (2000)

Glockner, G. et al. Sequence and analysis of chromosome 2 of Dictyostelium discoideum. Nature 418, 79–85 (2002)

Wood, V., Rutherford, K. M., Ivens, A., Rajandream, M. A. & Barrell, B. A re-annotation of the Saccharomyces cerevisiae genome. Comp. Funct. Genom. 2, 143–154 (2001)

Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408, 796–815 (2000)

Emanuelsson, O., Nielsen, H., Brunak, S. & von Heijne, G. Predicting subcellular localization of proteins based on their N-terminal amino acid sequence. J. Mol. Biol. 300, 1005–1016 (2000)

Scharfe, C. et al. MITOP, the mitochondrial proteome database: 2000 update. Nucleic Acids Res. 28, 155–158 (2000)

Claros, M. G. & Vincens, P. Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur. J. Biochem. 241, 779–786 (1996)

Apweiler, R. et al. The InterPro database, an integrated documentation resource for protein families, domains and functional sites. Nucleic Acids Res. 29, 37–40 (2001)

Bateman, A. et al. The Pfam protein families database. Nucleic Acids Res. 30, 276–280 (2002)

Krogh, A., Larsson, B., von Heijne, G. & Sonnhammer, E. L. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J. Mol. Biol. 305, 567–580 (2001)

Nielsen, H., Engelbrecht, J., Brunak, S. & von Heijne, G. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 10, 1–6 (1997)

Carlton, J. M. et al. Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium Yoelii yoelii. Nature 419, 512–519 (2002)