Nature 455, 799-803 (9 October 2008) | doi:10.1038/nature07306; Received 17 January 2008; Accepted 30 July 2008

The genome of the simian and human malaria parasite Plasmodium knowlesi

A. Pain1,14, U. Böhme1,14, A. E. Berry1,14, K. Mungall1, R. D. Finn1, A. P. Jackson1, T. Mourier2, J. Mistry1, E. M. Pasini3, M. A. Aslett1, S. Balasubrammaniam1, K. Borgwardt4, K. Brooks1, C. Carret1, T. J. Carver1, I. Cherevach1, T. Chillingworth1, T. G. Clark1,5, M. R. Galinski6, N. Hall7, D. Harper1, D. Harris1, H. Hauser1, A. Ivens1, C. S. Janssen8, T. Keane1, N. Larke1, S. Lapp6, M. Marti9, S. Moule1, I. M. Meyer10, D. Ormond1, N. Peters1, M. Sanders1, S. Sanders1, T. J. Sargeant11,12, M. Simmonds1, F. Smith1, R. Squares1, S. Thurston1, A. R. Tivey1, D. Walker1, B. White1, E. Zuiderwijk1, C. Churcher1, M. A. Quail1, A. F. Cowman11, C. M. R. Turner8, M. A. Rajandream1, C. H. M. Kocken3, A. W. Thomas3, C. I. Newbold1,13, B. G. Barrell1 & M. Berriman1

  1. Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK
  2. Ancient DNA and Evolution Group, Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark
  3. Department of Parasitology, Biomedical Primate Research Centre, PO Box 3306, 2280 GH, Rijswijk, The Netherlands
  4. Machine Learning Group, Department of Engineering, University of Cambridge, Trumpington Street, Cambridge CB2 1PZ, UK
  5. Wellcome Trust Centre for Human genetic, University of Oxford, Roosevelt Drive, Oxford OX3 9BN, UK
  6. Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, Georgia 30329, USA
  7. School of Biological Sciences, University of Liverpool, PO Box 147, Liverpool L69 3BX, UK
  8. Institute of Biomedical and Life Sciences and Wellcome Centre for Molecular Parasitology, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK
  9. Department of Immunology and Infectious Diseases, Harvard School of Public Health, 677 Huntington Avenue, Boston, Massachusetts 02115, USA
  10. UBC Bioinformatics Centre and Department of Computer Science, University of British Columbia and Department of Medical Genetics, 2366 Main Mall, British Columbia, Vancouver V6T 1Z4, Canada
  11. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
  12. The Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia
  13. The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK
  14. These authors contributed equally to this work.

Correspondence to: A. Pain1,14 Correspondence and requests for materials should be addressed to A.P. (Email: ap2@sanger.ac.uk).

This article is distributed under the terms of the Creative Commons Attribution-Non-Commercial-Share Alike licence (http://creativecommons.org/licenses/by-nc-sa/3.0/), which permits distribution, and reproduction in any medium, provided the original author and source are credited. This licence does not permit commercial exploitation, and derivative works must be licensed under the same or similar licence.

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, particularly in southeast Asia1, 2. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated3, and it has a close phylogenetic relationship to Plasmodium vivax 4, the second most important species of human malaria parasite (reviewed in ref. 4). Despite their relatedness, there are important phenotypic differences between them, such as host blood cell preference, absence of a dormant liver stage or 'hypnozoite' in P. knowlesi, and length of the asexual cycle (reviewed in ref. 4). Here we present an analysis of the P. knowlesi (H strain, Pk1(A+) clone5) nuclear genome sequence. This is the first monkey malaria parasite genome to be described, and it provides an opportunity for comparison with the recently completed P. vivax genome4 and other sequenced Plasmodium genomes6, 7, 8. In contrast to other Plasmodium genomes, putative variant antigen families are dispersed throughout the genome and are associated with intrachromosomal telomere repeats. One of these families, the KIRs9, contains sequences that collectively match over one-half of the host CD99 extracellular domain, which may represent an unusual form of molecular mimicry.


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