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  • A Corrigendum to this article was published on 01 March 2007
  • A Corrigendum to this article was published on 01 April 2007

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Abstract

Infections with the malaria parasite Plasmodium falciparum result in more than 1 million deaths each year worldwide1. Deciphering the evolutionary history and genetic variation of P. falciparum is critical for understanding the evolution of drug resistance, identifying potential vaccine candidates and appreciating the effect of parasite variation on prevalence and severity of malaria in humans. Most studies of natural variation in P. falciparum have been either in depth over small genomic regions (up to the size of a small chromosome2) or genome wide but only at low resolution3. In an effort to complement these studies with genome-wide data, we undertook shotgun sequencing of a Ghanaian clinical isolate (with fivefold coverage), the IT laboratory isolate (with onefold coverage) and the chimpanzee parasite P. reichenowi (with twofold coverage). We compared these sequences with the fully sequenced P. falciparum 3D7 isolate genome4. We describe the most salient features of P. falciparum polymorphism and adaptive evolution with relation to gene function, transcript and protein expression and cellular localization. This analysis uncovers the primary evolutionary changes that have occurred since the P. falciparum–P. reichenowi speciation and changes that are occurring within P. falciparum.

NOTE: In the original version of this paper, the authors failed to acknowledge that sequencing of the P. falciparum IT laboratory isolate was funded by a European Union 6th Framework Program grant to the BioMalPar Consortium (contract number LSHP-LT-2004-503578). This error has been corrected in the PDF version of the article.

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  • 08 February 2007

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Acknowledgements

We thank the Pathogen Sequencing teams for producing the sequence data used in this study, P. Horrocks and B. Pinches for the supply of DNA from the IT isolate and M. Marti for the list of PEXEL motif–containing genes. This study was funded by the Wellcome Trust through its support of the Pathogen Sequencing Unit and E.T.D.'s group at the Wellcome Trust Sanger Institute.

Author information

Affiliations

  1. Informatics Division, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA Hinxton, UK.

    • Daniel C Jeffares
    • , Anthony V Cox
    • , James Stalker
    • , Catherine E Ingle
    • , Kyle Siebenthall
    •  & Emmanouil T Dermitzakis
  2. Pathogen Sequencing Unit, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA Hinxton, UK.

    • Arnab Pain
    • , Andrew Berry
    • , Michael A Quail
    •  & Matthew Berriman
  3. Biomedical Primate Research Centre, Lange Kleiweg 139, Rijswijk, Postbus 3306, 2280 GH Rijswijk, The Netherlands.

    • Alan Thomas
  4. Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.

    • Kyle Siebenthall
  5. St. George's, University of London, Cranmer Terrace, London SW17 ORE, UK.

    • Anne-Catrin Uhlemann
    •  & Sanjeev Krishna
  6. The Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK.

    • Sue Kyes
    •  & Chris Newbold

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Contributions

D.J. processed SSAHA data, produced diversity and evolutionary measures, analyzed the data and wrote the manuscript. E.T.D. and M.B. directed the project and assisted with analysis of the data and writing of the manuscript. A.P. and A.B. assisted with analysis and processing of the data and biological interpretation of the data. A.T. collected the P. reichenowi sample and extracted DNA. K.S. assisted with data processing and analysis. A.C. provided SSAHA mapping. J.S. assisted with data processing. C.I. resequenced genes and manually verified SNPs. A.-C.U. assisted with parasite DNA extraction. S. Krishna assisted in biological interpretation of the data and parasitology. C.N. shaped some of the initial ideas for the project, assisted in biological interpretation of the data and assisted with parasite DNA extraction. S. Kyes grew the IT parasite and purified and extracted DNA from parasites.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Emmanouil T Dermitzakis or Matthew Berriman.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    The distributions of dN/dS estimates are negatively skewed.

  2. 2.

    Supplementary Fig. 2

    Correlations of dN/dS and expression level are robust to the use of different expression data and to subsets of variation data called using SSAHA.

  3. 3.

    Supplementary Fig. 3

    Consistent relative differences in evolutionary rates between stage-specific genes were observed with protein and microarray data.

  4. 4.

    Supplementary Methods

Excel files

  1. 1.

    Supplementary Table 1

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DOI

https://doi.org/10.1038/ng1931

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