Skip to main content
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):55–63. doi: 10.1098/rstb.2001.1011

Orthology between the genomes of Plasmodium falciparum and rodent malaria parasites: possible practical applications.

A P Waters 1
PMCID: PMC1692921  PMID: 11839182

Abstract

The work of the consortium that has been formed to complete the entire sequence of the genome of a selected clone of the human malaria parasite, Plasmodium falciparum, is almost finished. Already huge tracts of the genome are available as fully assembled chromosomes or large contigs and the work of initial annotation is in an advanced state. Post-genomic research is in one sense the process of furthering the process of annotation, creating biological atlases and preliminary attempts to make global descriptions of gene transcription and proteome analysis are underway. Comparison between significant amounts of genome data from both closely, and more distantly related organisms, can facilitate the identification of genes themselves, coordinately regulated gene expression groups, gene function and genome organization. Models of malaria can fulfil these functions and in addition provide an experimental system wherein predictions can be tested and basic experimental investigations performed within numerous aspects of disease, pathology, parasite-host and parasite-vector interactions. Comparative genomics in Plasmodium has already been shown to have informative roles in the completion of annotation and the elucidation of gene function. These roles will be illustrated by example and used as the basis for a discussion of the utility of genome information and malaria models in realizing the desired product of Plasmodium genomics, the development of malaria therapies.

Full Text

The Full Text of this article is available as a PDF (113.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alm R. A., Bina J., Andrews B. M., Doig P., Hancock R. E., Trust T. J. Comparative genomics of Helicobacter pylori: analysis of the outer membrane protein families. Infect Immun. 2000 Jul;68(7):4155–4168. doi: 10.1128/iai.68.7.4155-4168.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Black M. E., Newcomb T. G., Wilson H. M., Loeb L. A. Creation of drug-specific herpes simplex virus type 1 thymidine kinase mutants for gene therapy. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3525–3529. doi: 10.1073/pnas.93.8.3525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Carlton J. M., Galinski M. R., Barnwell J. W., Dame J. B. Karyotype and synteny among the chromosomes of all four species of human malaria parasite. Mol Biochem Parasitol. 1999 Jun 25;101(1-2):23–32. doi: 10.1016/s0166-6851(99)00045-6. [DOI] [PubMed] [Google Scholar]
  5. Carlton J. M., Vinkenoog R., Waters A. P., Walliker D. Gene synteny in species of Plasmodium. Mol Biochem Parasitol. 1998 Jun 1;93(2):285–294. doi: 10.1016/s0166-6851(98)00043-7. [DOI] [PubMed] [Google Scholar]
  6. Carlton JM, Dame JB. The plasmodium vivax and P. berghei gene sequence tag projects. Parasitol Today. 2000 Oct;16(10):409–409. doi: 10.1016/s0169-4758(00)01781-6. [DOI] [PubMed] [Google Scholar]
  7. Carter R., Coulson A., Bhatti S., Taylor B. J., Elliott J. F. Predicted disulfide-bonded structures for three uniquely related proteins of Plasmodium falciparum, Pfs230, Pfs48/45 and Pf12. Mol Biochem Parasitol. 1995 May;71(2):203–210. doi: 10.1016/0166-6851(94)00054-q. [DOI] [PubMed] [Google Scholar]
  8. Cowman A. F., Baldi D. L., Healer J., Mills K. E., O'Donnell R. A., Reed M. B., Triglia T., Wickham M. E., Crabb B. S. Functional analysis of proteins involved in Plasmodium falciparum merozoite invasion of red blood cells. FEBS Lett. 2000 Jun 30;476(1-2):84–88. doi: 10.1016/s0014-5793(00)01703-8. [DOI] [PubMed] [Google Scholar]
  9. Dessens J. T., Beetsma A. L., Dimopoulos G., Wengelnik K., Crisanti A., Kafatos F. C., Sinden R. E. CTRP is essential for mosquito infection by malaria ookinetes. EMBO J. 1999 Nov 15;18(22):6221–6227. doi: 10.1093/emboj/18.22.6221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Duffy P. E., Kaslow D. C. A novel malaria protein, Pfs28, and Pfs25 are genetically linked and synergistic as falciparum malaria transmission-blocking vaccines. Infect Immun. 1997 Mar;65(3):1109–1113. doi: 10.1128/iai.65.3.1109-1113.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Elliott J. F., Albrecht G. R., Gilladoga A., Handunnetti S. M., Neequaye J., Lallinger G., Minjas J. N., Howard R. J. Genes for Plasmodium falciparum surface antigens cloned by expression in COS cells. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6363–6367. doi: 10.1073/pnas.87.16.6363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Force A., Lynch M., Pickett F. B., Amores A., Yan Y. L., Postlethwait J. Preservation of duplicate genes by complementary, degenerative mutations. Genetics. 1999 Apr;151(4):1531–1545. doi: 10.1093/genetics/151.4.1531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gardner M. J., Tettelin H., Carucci D. J., Cummings L. M., Aravind L., Koonin E. V., Shallom S., Mason T., Yu K., Fujii C. Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science. 1998 Nov 6;282(5391):1126–1132. doi: 10.1126/science.282.5391.1126. [DOI] [PubMed] [Google Scholar]
  14. Goonewardene R., Daily J., Kaslow D., Sullivan T. J., Duffy P., Carter R., Mendis K., Wirth D. Transfection of the malaria parasite and expression of firefly luciferase. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5234–5236. doi: 10.1073/pnas.90.11.5234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Janse C. J., Carlton J. M., Walliker D., Waters A. P. Conserved location of genes on polymorphic chromosomes of four species of malaria parasites. Mol Biochem Parasitol. 1994 Dec;68(2):285–296. doi: 10.1016/0166-6851(94)90173-2. [DOI] [PubMed] [Google Scholar]
  16. Janssen C. S., Barrett M. P., Lawson D., Quail M. A., Harris D., Bowman S., Phillips R. S., Turner C. M. Gene discovery in Plasmodium chabaudi by genome survey sequencing. Mol Biochem Parasitol. 2001 Apr 6;113(2):251–260. doi: 10.1016/s0166-6851(01)00224-9. [DOI] [PubMed] [Google Scholar]
  17. Kappe S., Bruderer T., Gantt S., Fujioka H., Nussenzweig V., Ménard R. Conservation of a gliding motility and cell invasion machinery in Apicomplexan parasites. J Cell Biol. 1999 Nov 29;147(5):937–944. doi: 10.1083/jcb.147.5.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kerr J. R. Cell adhesion molecules in the pathogenesis of and host defence against microbial infection. Mol Pathol. 1999 Aug;52(4):220–230. doi: 10.1136/mp.52.4.220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kocken C. H., Jansen J., Kaan A. M., Beckers P. J., Ponnudurai T., Kaslow D. C., Konings R. N., Schoenmakers J. G. Cloning and expression of the gene coding for the transmission blocking target antigen Pfs48/45 of Plasmodium falciparum. Mol Biochem Parasitol. 1993 Sep;61(1):59–68. doi: 10.1016/0166-6851(93)90158-t. [DOI] [PubMed] [Google Scholar]
  20. Kocken C. H., van der Wel A., Thomas A. W. Plasmodium cynomolgi: transfection of blood-stage parasites using heterologous DNA constructs. Exp Parasitol. 1999 Sep;93(1):58–60. doi: 10.1006/expr.1999.4430. [DOI] [PubMed] [Google Scholar]
  21. Kumar N., Carter R. Biosynthesis of the target antigens of antibodies blocking transmission of Plasmodium falciparum. Mol Biochem Parasitol. 1984 Nov;13(3):333–342. doi: 10.1016/0166-6851(84)90124-5. [DOI] [PubMed] [Google Scholar]
  22. Kumar N. Target antigens of malaria transmission blocking immunity exist as a stable membrane bound complex. Parasite Immunol. 1987 May;9(3):321–335. doi: 10.1111/j.1365-3024.1987.tb00511.x. [DOI] [PubMed] [Google Scholar]
  23. Lavon I., Goldberg I., Amit S., Landsman L., Jung S., Tsuberi B. Z., Barshack I., Kopolovic J., Galun E., Bujard H. High susceptibility to bacterial infection, but no liver dysfunction, in mice compromised for hepatocyte NF-kappaB activation. Nat Med. 2000 May;6(5):573–577. doi: 10.1038/75057. [DOI] [PubMed] [Google Scholar]
  24. McCutchan T. F., Dame J. B., Miller L. H., Barnwell J. Evolutionary relatedness of Plasmodium species as determined by the structure of DNA. Science. 1984 Aug 24;225(4664):808–811. doi: 10.1126/science.6382604. [DOI] [PubMed] [Google Scholar]
  25. Mota M. M., Jarra W., Hirst E., Patnaik P. K., Holder A. A. Plasmodium chabaudi-infected erythrocytes adhere to CD36 and bind to microvascular endothelial cells in an organ-specific way. Infect Immun. 2000 Jul;68(7):4135–4144. doi: 10.1128/iai.68.7.4135-4144.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mota M. M., Thathy V., Nussenzweig R. S., Nussenzweig V. Gene targeting in the rodent malaria parasite Plasmodium yoelii. Mol Biochem Parasitol. 2001 Apr 6;113(2):271–278. doi: 10.1016/s0166-6851(01)00228-6. [DOI] [PubMed] [Google Scholar]
  27. Ménard R., Sultan A. A., Cortes C., Altszuler R., van Dijk M. R., Janse C. J., Waters A. P., Nussenzweig R. S., Nussenzweig V. Circumsporozoite protein is required for development of malaria sporozoites in mosquitoes. Nature. 1997 Jan 23;385(6614):336–340. doi: 10.1038/385336a0. [DOI] [PubMed] [Google Scholar]
  28. Phillips R. S., Brannan L. R., Balmer P., Neuville P. Antigenic variation during malaria infection--the contribution from the murine parasite Plasmodium chabaudi. Parasite Immunol. 1997 Sep;19(9):427–434. doi: 10.1046/j.1365-3024.1997.d01-239.x. [DOI] [PubMed] [Google Scholar]
  29. Preiser P. R., Jarra W., Capiod T., Snounou G. A rhoptry-protein-associated mechanism of clonal phenotypic variation in rodent malaria. Nature. 1999 Apr 15;398(6728):618–622. doi: 10.1038/19309. [DOI] [PubMed] [Google Scholar]
  30. Rener J., Graves P. M., Carter R., Williams J. L., Burkot T. R. Target antigens of transmission-blocking immunity on gametes of plasmodium falciparum. J Exp Med. 1983 Sep 1;158(3):976–981. doi: 10.1084/jem.158.3.976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rubin G. M., Yandell M. D., Wortman J. R., Gabor Miklos G. L., Nelson C. R., Hariharan I. K., Fortini M. E., Li P. W., Apweiler R., Fleischmann W. Comparative genomics of the eukaryotes. Science. 2000 Mar 24;287(5461):2204–2215. doi: 10.1126/science.287.5461.2204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sultan A. A., Thathy V., Frevert U., Robson K. J., Crisanti A., Nussenzweig V., Nussenzweig R. S., Ménard R. TRAP is necessary for gliding motility and infectivity of plasmodium sporozoites. Cell. 1997 Aug 8;90(3):511–522. doi: 10.1016/s0092-8674(00)80511-5. [DOI] [PubMed] [Google Scholar]
  33. Sultan A. A., Thathy V., de Koning-Ward T. F., Nussenzweig V. Complementation of Plasmodium berghei TRAP knockout parasites using human dihydrofolate reductase gene as a selectable marker. Mol Biochem Parasitol. 2001 Mar;113(1):151–156. doi: 10.1016/s0166-6851(01)00209-2. [DOI] [PubMed] [Google Scholar]
  34. Tachibana M., Tsuboi T., Templeton T. J., Kaneko O., Torii M. Presence of three distinct ookinete surface protein genes, Pos25, Pos28-1, and Pos28-2, in Plasmodium ovale. Mol Biochem Parasitol. 2001 Apr 6;113(2):341–344. doi: 10.1016/s0166-6851(01)00231-6. [DOI] [PubMed] [Google Scholar]
  35. Templeton T. J., Kaslow D. C. Identification of additional members define a Plasmodium falciparum gene superfamily which includes Pfs48/45 and Pfs230. Mol Biochem Parasitol. 1999 Jun 25;101(1-2):223–227. doi: 10.1016/s0166-6851(99)00066-3. [DOI] [PubMed] [Google Scholar]
  36. Thompson J., Janse C. J., Waters A. P. Comparative genomics in Plasmodium: a tool for the identification of genes and functional analysis. Mol Biochem Parasitol. 2001 Dec;118(2):147–154. doi: 10.1016/s0166-6851(01)00377-2. [DOI] [PubMed] [Google Scholar]
  37. Tomas A. M., Margos G., Dimopoulos G., van Lin L. H., de Koning-Ward T. F., Sinha R., Lupetti P., Beetsma A. L., Rodriguez M. C., Karras M. P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO J. 2001 Aug 1;20(15):3975–3983. doi: 10.1093/emboj/20.15.3975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  39. Vermeulen A. N., Ponnudurai T., Beckers P. J., Verhave J. P., Smits M. A., Meuwissen J. H. Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission-blocking antibodies in the mosquito. J Exp Med. 1985 Nov 1;162(5):1460–1476. doi: 10.1084/jem.162.5.1460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wengelnik K., Spaccapelo R., Naitza S., Robson K. J., Janse C. J., Bistoni F., Waters A. P., Crisanti A. The A-domain and the thrombospondin-related motif of Plasmodium falciparum TRAP are implicated in the invasion process of mosquito salivary glands. EMBO J. 1999 Oct 1;18(19):5195–5204. doi: 10.1093/emboj/18.19.5195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wu T., Black C. G., Wang L., Hibbs A. R., Coppel R. L. Lack of sequence diversity in the gene encoding merozoite surface protein 5 of Plasmodium falciparum. Mol Biochem Parasitol. 1999 Oct 15;103(2):243–250. doi: 10.1016/s0166-6851(99)00134-6. [DOI] [PubMed] [Google Scholar]
  42. Yuda M., Sakaida H., Chinzei Y. Targeted disruption of the plasmodium berghei CTRP gene reveals its essential role in malaria infection of the vector mosquito. J Exp Med. 1999 Dec 6;190(11):1711–1716. doi: 10.1084/jem.190.11.1711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. de Koning-Ward T. F., Fidock D. A., Thathy V., Menard R., van Spaendonk R. M., Waters A. P., Janse C. J. The selectable marker human dihydrofolate reductase enables sequential genetic manipulation of the Plasmodium berghei genome. Mol Biochem Parasitol. 2000 Mar 5;106(2):199–212. doi: 10.1016/s0166-6851(99)00189-9. [DOI] [PubMed] [Google Scholar]
  44. de Koning-Ward T. F., Janse C. J., Waters A. P. The development of genetic tools for dissecting the biology of malaria parasites. Annu Rev Microbiol. 2000;54:157–185. doi: 10.1146/annurev.micro.54.1.157. [DOI] [PubMed] [Google Scholar]
  45. del Portillo H. A., Fernandez-Becerra C., Bowman S., Oliver K., Preuss M., Sanchez C. P., Schneider N. K., Villalobos J. M., Rajandream M. A., Harris D. A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax. Nature. 2001 Apr 12;410(6830):839–842. doi: 10.1038/35071118. [DOI] [PubMed] [Google Scholar]
  46. van Dijk M. R., Janse C. J., Thompson J., Waters A. P., Braks J. A., Dodemont H. J., Stunnenberg H. G., van Gemert G. J., Sauerwein R. W., Eling W. A central role for P48/45 in malaria parasite male gamete fertility. Cell. 2001 Jan 12;104(1):153–164. doi: 10.1016/s0092-8674(01)00199-4. [DOI] [PubMed] [Google Scholar]
  47. van Dijk M. R., Janse C. J., Waters A. P. Expression of a Plasmodium gene introduced into subtelomeric regions of Plasmodium berghei chromosomes. Science. 1996 Feb 2;271(5249):662–665. doi: 10.1126/science.271.5249.662. [DOI] [PubMed] [Google Scholar]
  48. van Dijk M. R., Waters A. P., Janse C. J. Stable transfection of malaria parasite blood stages. Science. 1995 Jun 2;268(5215):1358–1362. doi: 10.1126/science.7761856. [DOI] [PubMed] [Google Scholar]
  49. van Lin L. H., Pace T., Janse C. J., Birago C., Ramesar J., Picci L., Ponzi M., Waters A. P. Interspecies conservation of gene order and intron-exon structure in a genomic locus of high gene density and complexity in Plasmodium. Nucleic Acids Res. 2001 May 15;29(10):2059–2068. doi: 10.1093/nar/29.10.2059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. van Lin L. H., Pace T., Janse C. J., Scotti R., Ponzi M. A long range restriction map of chromosome 5 of Plasmodium berghei demonstrates a chromosome specific symmetrical subtelomeric organisation. Mol Biochem Parasitol. 1997 May;86(1):111–115. [PubMed] [Google Scholar]
  51. van der Heyde H. C., Bauer P., Sun G., Chang W. L., Yin L., Fuseler J., Granger D. N. Assessing vascular permeability during experimental cerebral malaria by a radiolabeled monoclonal antibody technique. Infect Immun. 2001 May;69(5):3460–3465. doi: 10.1128/IAI.69.5.3460-3465.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. van der Wel A. M., Tomás A. M., Kocken C. H., Malhotra P., Janse C. J., Waters A. P., Thomas A. W. Transfection of the primate malaria parasite Plasmodium knowlesi using entirely heterologous constructs. J Exp Med. 1997 Apr 21;185(8):1499–1503. doi: 10.1084/jem.185.8.1499. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES