plasmodium genomics

Nature 419, 498-511 (3 October 2002) | doi:10.1038/nature01097; Received 31 July 2002; Accepted 2 September 2002

Genome sequence of the human malaria parasite Plasmodium falciparum

Malcolm J. Gardner1, Neil Hall2, Eula Fung3, Owen White1, Matthew Berriman2, Richard W. Hyman3, Jane M. Carlton1, Arnab Pain2, Karen E. Nelson1, Sharen Bowman2,14, Ian T. Paulsen1, Keith James2, Jonathan A. Eisen1, Kim Rutherford2, Steven L. Salzberg1, Alister Craig4, Sue Kyes5, Man-Suen Chan5, Vishvanath Nene1, Shamira J. Shallom1, Bernard Suh1, Jeremy Peterson1, Sam Angiuoli1, Mihaela Pertea1, Jonathan Allen1, Jeremy Selengut1, Daniel Haft1, Michael W. Mather6, Akhil B. Vaidya6, David M. A. Martin7, Alan H. Fairlamb7, Martin J. Fraunholz8, David S. Roos8, Stuart A. Ralph9, Geoffrey I. McFadden9, Leda M. Cummings1, G. Mani Subramanian10, Chris Mungall11, J. Craig Venter12, Daniel J. Carucci13, Stephen L. Hoffman13,14, Chris Newbold5, Ronald W. Davis3, Claire M. Fraser1 & Bart Barrell2

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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.

  1. The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, Maryland 20850, USA
  2. The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
  3. Stanford Genome Technology Center, 855 California Avenue, Palo Alto, California 94304, USA
  4. Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK
  5. University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DU, UK
  6. Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, Pennsylvania 19129, USA
  7. School of Life Sciences, The Wellcome Trust Biocentre, The University of Dundee, Dundee DD1 5EH, UK
  8. Department of Biology and Genomics Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6018, USA
  9. Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Melbourne, VIC 3010, Australia
  10. Celera Genomics, 45 West Gude Drive, Rockville, Maryland 20850, USA
  11. Department of Molecular and Cellular Biology, Berkeley Drosophila Genome Project, University of California, Berkeley, California 94720, USA
  12. The Center for the Advancement of Genomics, 1901 Research Boulevard, 6th Floor, Rockville, Maryland 20850, USA
  13. Malaria Program, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, Maryland 20910-7500, USA
  14. Present addresses: Syngenta, Jealott's Hill International Research Centre, Bracknell, RG42 6EY, UK (S.B.); Sanaria, 308 Argosy Drive, Gaithersburg, Maryland 20878, USA (S.L.H.).

Correspondence to: Malcolm J. Gardner1 Correspondence and requests for materials should be addressed to M.J.G. (e-mail: Email: gardner@tigr.org). Sequences and annotation are available at the following websites: PlasmoDB (http://plasmodb.org), The Institute for Genomic Research (http://www.tigr.org), the Wellcome Trust Sanger Institute (http://www.sanger.ac.uk/Projects/Protozoa/), and the Stanford Genome Technology Center (http://www-sequence.stanford.edu/group/malaria). Chromosome sequences were submitted to EMBL or GenBank with accession numbers AL844501–AL844509 (chromosomes 1, 3–9 and 13), AE001362.2 (chromosome 2), AE014185–AE014187 (chromosomes 10, 11 and 14) and AE014188 (chromosome 12).