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 Asia. Plasmodium knowlesi was the first malaria parasite species in which antigenic variation was demonstrated, and it has a close phylogenetic relationship to Plasmodium vivax, 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+) clone) 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 genome and other sequenced Plasmodium genomes. 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 KIRs, 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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Acknowledgements We acknowledge the support of the Wellcome Trust Sanger Institute core sequencing and informatics groups. The study was funded by the Wellcome Trust through its support to the Pathogen Sequencing Unit at the Wellcome Trust Sanger Institute. We thank J. Barnwell for providing the Pk1(A1) clone of the H strain of the parasite for the generation of genomic DNA by A. Thomas. We thank A. Voorberg-vd Wel (BPRC, Rijswijk) for technical assistance. We thank D. Fergusson for providing us with the electron micrograph image of the erythrocyte, used in Fig. 2. Part of this work was supported by the Netherlands Organization for Scientific Research, NIH, BioMalPar and the Virimal contract. This work is dedicated to the memory of Marie-Adele Rajandream.
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