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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2002 Jan 29;357(1417):35–46. doi: 10.1098/rstb.2001.1047

Mining the Plasmodium genome database to define organellar function: what does the apicoplast do?

David S Roos 1, Michael J Crawford 1, Robert G K Donald 1, Martin Fraunholz 1, Omar S Harb 1, Cynthia Y He 1, Jessica C Kissinger 1, Michael K Shaw 1, Boris Striepen 1
PMCID: PMC1692924  PMID: 11839180

Abstract

Apicomplexan species constitute a diverse group of parasitic protozoa, which are responsible for a wide range of diseases in many organisms. Despite differences in the diseases they cause, these parasites share an underlying biology, from the genetic controls used to differentiate through the complex parasite life cycle, to the basic biochemical pathways employed for intracellular survival, to the distinctive cell biology necessary for host cell attachment and invasion. Different parasites lend themselves to the study of different aspects of parasite biology: Eimeria for biochemical studies, Toxoplasma for molecular genetic and cell biological investigation, etc. The Plasmodium falciparum Genome Project contributes the first large-scale genomic sequence for an apicomplexan parasite. The Plasmodium Genome Database (http://PlasmoDB.org) has been designed to permit individual investigators to ask their own questions, even prior to formal release of the reference P. falciparum genome sequence. As a case in point, PlasmoDB has been exploited to identify metabolic pathways associated with the apicomplexan plastid, or 'apicoplast' - an essential organelle derived by secondary endosymbiosis of an alga, and retention of the algal plastid.

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Selected References

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  1. Aikawa M. Parasitological review. Plasmodium: the fine structure of malarial parasites. Exp Parasitol. 1971 Oct;30(2):284–320. doi: 10.1016/0014-4894(71)90094-4. [DOI] [PubMed] [Google Scholar]
  2. Ajioka J. W., Boothroyd J. C., Brunk B. P., Hehl A., Hillier L., Manger I. D., Marra M., Overton G. C., Roos D. S., Wan K. L. Gene discovery by EST sequencing in Toxoplasma gondii reveals sequences restricted to the Apicomplexa. Genome Res. 1998 Jan;8(1):18–28. doi: 10.1101/gr.8.1.18. [DOI] [PubMed] [Google Scholar]
  3. Apt K. E., Clendennen S. K., Powers D. A., Grossman A. R. The gene family encoding the fucoxanthin chlorophyll proteins from the brown alga Macrocystis pyrifera. Mol Gen Genet. 1995 Feb 20;246(4):455–464. doi: 10.1007/BF00290449. [DOI] [PubMed] [Google Scholar]
  4. Beckers C. J., Roos D. S., Donald R. G., Luft B. J., Schwab J. C., Cao Y., Joiner K. A. Inhibition of cytoplasmic and organellar protein synthesis in Toxoplasma gondii. Implications for the target of macrolide antibiotics. J Clin Invest. 1995 Jan;95(1):367–376. doi: 10.1172/JCI117665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black M. W., Boothroyd J. C. Development of a stable episomal shuttle vector for Toxoplasma gondii. J Biol Chem. 1998 Feb 13;273(7):3972–3979. doi: 10.1074/jbc.273.7.3972. [DOI] [PubMed] [Google Scholar]
  6. Blanchard J. L., Hicks J. S. The non-photosynthetic plastid in malarial parasites and other apicomplexans is derived from outside the green plastid lineage. J Eukaryot Microbiol. 1999 Jul-Aug;46(4):367–375. doi: 10.1111/j.1550-7408.1999.tb04615.x. [DOI] [PubMed] [Google Scholar]
  7. Bowman S., Lawson D., Basham D., Brown D., Chillingworth T., Churcher C. M., Craig A., Davies R. M., Devlin K., Feltwell T. The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Nature. 1999 Aug 5;400(6744):532–538. doi: 10.1038/22964. [DOI] [PubMed] [Google Scholar]
  8. Brennan C. M., Gallouzi I. E., Steitz J. A. Protein ligands to HuR modulate its interaction with target mRNAs in vivo. J Cell Biol. 2000 Oct 2;151(1):1–14. doi: 10.1083/jcb.151.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carruthers V. B., Sibley L. D. Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. Eur J Cell Biol. 1997 Jun;73(2):114–123. [PubMed] [Google Scholar]
  10. Cavalier-Smith T. Kingdom protozoa and its 18 phyla. Microbiol Rev. 1993 Dec;57(4):953–994. doi: 10.1128/mr.57.4.953-994.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cline K., Henry R. Import and routing of nucleus-encoded chloroplast proteins. Annu Rev Cell Dev Biol. 1996;12:1–26. doi: 10.1146/annurev.cellbio.12.1.1. [DOI] [PubMed] [Google Scholar]
  12. Coppens I., Sinai A. P., Joiner K. A. Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated endocytosis for cholesterol acquisition. J Cell Biol. 2000 Apr 3;149(1):167–180. doi: 10.1083/jcb.149.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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. 2000 Nov;113(Pt 22):3969–3977. doi: 10.1242/jcs.113.22.3969. [DOI] [PubMed] [Google Scholar]
  14. Delwiche C. F., Kuhsel M., Palmer J. D. Phylogenetic analysis of tufA sequences indicates a cyanobacterial origin of all plastids. Mol Phylogenet Evol. 1995 Jun;4(2):110–128. doi: 10.1006/mpev.1995.1012. [DOI] [PubMed] [Google Scholar]
  15. Di Cristina M., Spaccapelo R., Soldati D., Bistoni F., Crisanti A. Two conserved amino acid motifs mediate protein targeting to the micronemes of the apicomplexan parasite Toxoplasma gondii. Mol Cell Biol. 2000 Oct;20(19):7332–7341. doi: 10.1128/mcb.20.19.7332-7341.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Donald R. G., Roos D. S. Gene knock-outs and allelic replacements in Toxoplasma gondii: HXGPRT as a selectable marker for hit-and-run mutagenesis. Mol Biochem Parasitol. 1998 Mar 15;91(2):295–305. doi: 10.1016/s0166-6851(97)00210-7. [DOI] [PubMed] [Google Scholar]
  17. Donald R. G., Roos D. S. Homologous recombination and gene replacement at the dihydrofolate reductase-thymidylate synthase locus in Toxoplasma gondii. Mol Biochem Parasitol. 1994 Feb;63(2):243–253. doi: 10.1016/0166-6851(94)90060-4. [DOI] [PubMed] [Google Scholar]
  18. Eisenreich W., Rohdich F., Bacher A. Deoxyxylulose phosphate pathway to terpenoids. Trends Plant Sci. 2001 Feb;6(2):78–84. doi: 10.1016/s1360-1385(00)01812-4. [DOI] [PubMed] [Google Scholar]
  19. 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. 2001 Mar;18(3):418–426. doi: 10.1093/oxfordjournals.molbev.a003818. [DOI] [PubMed] [Google Scholar]
  20. Feagin J. E. The extrachromosomal DNAs of apicomplexan parasites. Annu Rev Microbiol. 1994;48:81–104. doi: 10.1146/annurev.mi.48.100194.000501. [DOI] [PubMed] [Google Scholar]
  21. Fichera M. E., Bhopale M. K., Roos D. S. In vitro assays elucidate peculiar kinetics of clindamycin action against Toxoplasma gondii. Antimicrob Agents Chemother. 1995 Jul;39(7):1530–1537. doi: 10.1128/aac.39.7.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Fichera M. E., Roos D. S. A plastid organelle as a drug target in apicomplexan parasites. Nature. 1997 Nov 27;390(6658):407–409. doi: 10.1038/37132. [DOI] [PubMed] [Google Scholar]
  23. Fletcher C. The Plasmodium falciparum Genome Project. Parasitol Today. 1998 Sep;14(9):342–344. doi: 10.1016/s0169-4758(98)01300-3. [DOI] [PubMed] [Google Scholar]
  24. Gajadhar A. A., Marquardt W. C., Hall R., Gunderson J., Ariztia-Carmona E. V., Sogin M. L. Ribosomal RNA sequences of Sarcocystis muris, Theileria annulata and Crypthecodinium cohnii reveal evolutionary relationships among apicomplexans, dinoflagellates, and ciliates. Mol Biochem Parasitol. 1991 Mar;45(1):147–154. doi: 10.1016/0166-6851(91)90036-6. [DOI] [PubMed] [Google Scholar]
  25. Gauthier J. D., Feig B., Vasta G. R. Effect of fetal bovine serum glycoproteins on the in vitro proliferation of the oyster parasite Perkinsus marinus: development of a fully defined medium. J Eukaryot Microbiol. 1995 May-Jun;42(3):307–313. doi: 10.1111/j.1550-7408.1995.tb01585.x. [DOI] [PubMed] [Google Scholar]
  26. Geary T. G., Divo A. A., Jensen J. B. Stage specific actions of antimalarial drugs on Plasmodium falciparum in culture. Am J Trop Med Hyg. 1989 Mar;40(3):240–244. doi: 10.4269/ajtmh.1989.40.240. [DOI] [PubMed] [Google Scholar]
  27. Hager K. M., Striepen B., Tilney L. G., Roos D. S. The nuclear envelope serves as an intermediary between the ER and Golgi complex in the intracellular parasite Toxoplasma gondii. J Cell Sci. 1999 Aug;112(Pt 16):2631–2638. doi: 10.1242/jcs.112.16.2631. [DOI] [PubMed] [Google Scholar]
  28. Haucke V., Schatz G. Import of proteins into mitochondria and chloroplasts. Trends Cell Biol. 1997 Mar;7(3):103–106. doi: 10.1016/S0962-8924(96)10052-0. [DOI] [PubMed] [Google Scholar]
  29. He C. Y., Shaw M. K., Pletcher C. H., Striepen B., Tilney L. G., Roos D. S. A plastid segregation defect in the protozoan parasite Toxoplasma gondii. EMBO J. 2001 Feb 1;20(3):330–339. doi: 10.1093/emboj/20.3.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Jelenska J., Crawford M. J., Harb O. S., Zuther E., Haselkorn R., Roos D. S., Gornicki P. Subcellular localization of acetyl-CoA carboxylase in the apicomplexan parasite Toxoplasma gondii. Proc Natl Acad Sci U S A. 2001 Feb 13;98(5):2723–2728. doi: 10.1073/pnas.051629998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Jomaa H., Wiesner J., Sanderbrand S., Altincicek B., Weidemeyer C., Hintz M., Türbachova I., Eberl M., Zeidler J., Lichtenthaler H. K. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science. 1999 Sep 3;285(5433):1573–1576. doi: 10.1126/science.285.5433.1573. [DOI] [PubMed] [Google Scholar]
  32. Köhler S., Delwiche C. F., Denny P. W., Tilney L. G., Webster P., Wilson R. J., Palmer J. D., Roos D. S. A plastid of probable green algal origin in Apicomplexan parasites. Science. 1997 Mar 7;275(5305):1485–1489. doi: 10.1126/science.275.5305.1485. [DOI] [PubMed] [Google Scholar]
  33. Laughon B. E., Allaudeen H. S., Becker J. M., Current W. L., Feinberg J., Frenkel J. K., Hafner R., Hughes W. T., Laughlin C. A., Meyers J. D. From the National Institutes of Health. Summary of the workshop on future directions in discovery and development of therapeutic agents for opportunistic infections associated with AIDS. J Infect Dis. 1991 Aug;164(2):244–251. doi: 10.1093/infdis/164.2.244. [DOI] [PubMed] [Google Scholar]
  34. Levine N. D. Progress in taxonomy of the Apicomplexan protozoa. J Protozool. 1988 Nov;35(4):518–520. doi: 10.1111/j.1550-7408.1988.tb04141.x. [DOI] [PubMed] [Google Scholar]
  35. Lingelbach K., Joiner K. A. The parasitophorous vacuole membrane surrounding Plasmodium and Toxoplasma: an unusual compartment in infected cells. J Cell Sci. 1998 Jun;111(Pt 11):1467–1475. doi: 10.1242/jcs.111.11.1467. [DOI] [PubMed] [Google Scholar]
  36. Luft B. J., Remington J. S. Toxoplasmic encephalitis in AIDS. Clin Infect Dis. 1992 Aug;15(2):211–222. doi: 10.1093/clinids/15.2.211. [DOI] [PubMed] [Google Scholar]
  37. Martin W., Stoebe B., Goremykin V., Hapsmann S., Hasegawa M., Kowallik K. V. Gene transfer to the nucleus and the evolution of chloroplasts. Nature. 1998 May 14;393(6681):162–165. doi: 10.1038/30234. [DOI] [PubMed] [Google Scholar]
  38. Martin W, Herrmann RG. Gene transfer from organelles to the nucleus: how much, what happens, and Why? . Plant Physiol. 1998 Sep;118(1):9–17. doi: 10.1104/pp.118.1.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. McAuley J., Boyer K. M., Patel D., Mets M., Swisher C., Roizen N., Wolters C., Stein L., Stein M., Schey W. Early and longitudinal evaluations of treated infants and children and untreated historical patients with congenital toxoplasmosis: the Chicago Collaborative Treatment Trial. Clin Infect Dis. 1994 Jan;18(1):38–72. doi: 10.1093/clinids/18.1.38. [DOI] [PubMed] [Google Scholar]
  40. McFadden G. I. Plastids and protein targeting. J Eukaryot Microbiol. 1999 Jul-Aug;46(4):339–346. doi: 10.1111/j.1550-7408.1999.tb04613.x. [DOI] [PubMed] [Google Scholar]
  41. McFadden G. I., Reith M. E., Munholland J., Lang-Unnasch N. Plastid in human parasites. Nature. 1996 Jun 6;381(6582):482–482. doi: 10.1038/381482a0. [DOI] [PubMed] [Google Scholar]
  42. McFadden G. I., Roos D. S. Apicomplexan plastids as drug targets. Trends Microbiol. 1999 Aug;7(8):328–333. doi: 10.1016/s0966-842x(99)01547-4. [DOI] [PubMed] [Google Scholar]
  43. Neupert W. Protein import into mitochondria. Annu Rev Biochem. 1997;66:863–917. doi: 10.1146/annurev.biochem.66.1.863. [DOI] [PubMed] [Google Scholar]
  44. Nielsen H., Engelbrecht J., Brunak S., von Heijne G. Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 1997 Jan;10(1):1–6. doi: 10.1093/protein/10.1.1. [DOI] [PubMed] [Google Scholar]
  45. Palmer J. D., Delwiche C. F. Second-hand chloroplasts and the case of the disappearing nucleus. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7432–7435. doi: 10.1073/pnas.93.15.7432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Pfefferkorn L. C., Pfefferkorn E. R. Toxoplasma gondii: genetic recombination between drug resistant mutants. Exp Parasitol. 1980 Dec;50(3):305–316. doi: 10.1016/0014-4894(80)90034-x. [DOI] [PubMed] [Google Scholar]
  47. Pilon M., Wienk H., Sips W., de Swaaf M., Talboom I., van 't Hof R., de Korte-Kool G., Demel R., Weisbeek P., de Kruijff B. Functional domains of the ferredoxin transit sequence involved in chloroplast import. J Biol Chem. 1995 Feb 24;270(8):3882–3893. doi: 10.1074/jbc.270.8.3882. [DOI] [PubMed] [Google Scholar]
  48. Roos D. S. Computational biology. Bioinformatics--trying to swim in a sea of data. Science. 2001 Feb 16;291(5507):1260–1261. doi: 10.1126/science.291.5507.1260. [DOI] [PubMed] [Google Scholar]
  49. Roos D. S., Crawford M. J., Donald R. G., Fohl L. M., Hager K. M., Kissinger J. C., Reynolds M. G., Striepen B., Sullivan W. J., Jr Transport and trafficking: Toxoplasma as a model for Plasmodium. Novartis Found Symp. 1999;226:176–198. doi: 10.1002/9780470515730.ch13. [DOI] [PubMed] [Google Scholar]
  50. Roos D. S., Crawford M. J., Donald R. G., Kissinger J. C., Klimczak L. J., Striepen B. Origin, targeting, and function of the apicomplexan plastid. Curr Opin Microbiol. 1999 Aug;2(4):426–432. doi: 10.1016/S1369-5274(99)80075-7. [DOI] [PubMed] [Google Scholar]
  51. Roos D. S., Donald R. G., Morrissette N. S., Moulton A. L. Molecular tools for genetic dissection of the protozoan parasite Toxoplasma gondii. Methods Cell Biol. 1994;45:27–63. doi: 10.1016/s0091-679x(08)61845-2. [DOI] [PubMed] [Google Scholar]
  52. Roos D. S., Sullivan W. J., Striepen B., Bohne W., Donald R. G. Tagging genes and trapping promoters in Toxoplasma gondii by insertional mutagenesis. Methods. 1997 Oct;13(2):112–122. doi: 10.1006/meth.1997.0504. [DOI] [PubMed] [Google Scholar]
  53. Schmatz D. M. The mannitol cycle in Eimeria. Parasitology. 1997;114 (Suppl):S81–S89. [PubMed] [Google Scholar]
  54. Schwartzbach S. D., Osafune T., Löffelhardt W. Protein import into cyanelles and complex chloroplasts. Plant Mol Biol. 1998 Sep;38(1-2):247–263. [PubMed] [Google Scholar]
  55. Shaw M. K., Tilney L. G. How individual cells develop from a syncytium: merogony in Theileria parva (Apicomplexa). J Cell Sci. 1992 Jan;101(Pt 1):109–123. doi: 10.1242/jcs.101.1.109. [DOI] [PubMed] [Google Scholar]
  56. Sheffield H. G., Melton M. L. The fine structure and reproduction of Toxoplasma gondii. J Parasitol. 1968 Apr;54(2):209–226. [PubMed] [Google Scholar]
  57. Siddall M. E. Hohlzylinders. Parasitol Today. 1992 Mar;8(3):90–91. doi: 10.1016/0169-4758(92)90244-v. [DOI] [PubMed] [Google Scholar]
  58. Sinden R. E. The cell biology of sexual development in plasmodium. Parasitology. 1983 Apr;86(Pt 4):7–28. doi: 10.1017/s0031182000050824. [DOI] [PubMed] [Google Scholar]
  59. Soll J., Tien R. Protein translocation into and across the chloroplastic envelope membranes. Plant Mol Biol. 1998 Sep;38(1-2):191–207. [PubMed] [Google Scholar]
  60. Somerville C., Browse J. Plant lipids: metabolism, mutants, and membranes. Science. 1991 Apr 5;252(5002):80–87. doi: 10.1126/science.252.5002.80. [DOI] [PubMed] [Google Scholar]
  61. Striepen B., He C. Y., Matrajt M., Soldati D., Roos D. S. Expression, selection, and organellar targeting of the green fluorescent protein in Toxoplasma gondii. Mol Biochem Parasitol. 1998 May 1;92(2):325–338. doi: 10.1016/s0166-6851(98)00011-5. [DOI] [PubMed] [Google Scholar]
  62. Striepen B., Soldati D., Garcia-Reguet N., Dubremetz J. F., Roos D. S. Targeting of soluble proteins to the rhoptries and micronemes in Toxoplasma gondii. Mol Biochem Parasitol. 2001 Mar;113(1):45–53. doi: 10.1016/s0166-6851(00)00379-0. [DOI] [PubMed] [Google Scholar]
  63. Tarleton R. L., Kissinger J. Parasite genomics: current status and future prospects. Curr Opin Immunol. 2001 Aug;13(4):395–402. doi: 10.1016/s0952-7915(00)00233-8. [DOI] [PubMed] [Google Scholar]
  64. Ullman B., Carter D. Hypoxanthine-guanine phosphoribosyltransferase as a therapeutic target in protozoal infections. Infect Agents Dis. 1995 Mar;4(1):29–40. [PubMed] [Google Scholar]
  65. 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. 2000 Oct 30;276(8):5483–5490. doi: 10.1074/jbc.M009452200. [DOI] [PubMed] [Google Scholar]
  66. 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. 2000 Apr 17;19(8):1794–1802. doi: 10.1093/emboj/19.8.1794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Weissig V., Vetro-Widenhouse T. S., Rowe T. C. Topoisomerase II inhibitors induce cleavage of nuclear and 35-kb plastid DNAs in the malarial parasite Plasmodium falciparum. DNA Cell Biol. 1997 Dec;16(12):1483–1492. doi: 10.1089/dna.1997.16.1483. [DOI] [PubMed] [Google Scholar]
  68. Wellems T. E. Molecular genetics of drug resistance in Plasmodium falciparum malaria. Parasitol Today. 1991 May;7(5):110–112. doi: 10.1016/0169-4758(91)90168-n. [DOI] [PubMed] [Google Scholar]
  69. Wilson R. J., Williamson D. H. Extrachromosomal DNA in the Apicomplexa. Microbiol Mol Biol Rev. 1997 Mar;61(1):1–16. doi: 10.1128/mmbr.61.1.1-16.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. 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. 2001 Nov;118(1):11–21. doi: 10.1016/s0166-6851(01)00359-0. [DOI] [PubMed] [Google Scholar]
  71. Zhu G., Marchewka M. J., Keithly J. S. Cryptosporidium parvum appears to lack a plastid genome. Microbiology. 2000 Feb;146(Pt 2):315–321. doi: 10.1099/00221287-146-2-315. [DOI] [PubMed] [Google Scholar]
  72. von Heijne G., Nishikawa K. Chloroplast transit peptides. The perfect random coil? FEBS Lett. 1991 Jan 14;278(1):1–3. doi: 10.1016/0014-5793(91)80069-f. [DOI] [PubMed] [Google Scholar]

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