A Comprehensive Survey of the Plasmodium Life Cycle by Genomic, Transcriptomic, and Proteomic Analyses

Neil Hall,^1* Marianna Karras,² J. Dale Raine,³ Jane M. Carlton,^4,5,6 Taco W. A. Kooij,² Matthew Berriman,¹ Laurence Florens,⁷ Christoph S. Janssen,⁸ Arnab Pain,¹ Georges K. Christophides,⁹ Keith James,¹ Kim Rutherford,¹ Barbara Harris,¹ David Harris,¹ Carol Churcher,¹ Michael A. Quail,¹ Doug Ormond,¹ Jon Doggett,¹ Holly E. Trueman,³ Jacqui Mendoza,³ Shelby L. Bidwell,⁴ Marie-Adele Rajandream,¹ Daniel J. Carucci,¹⁰ John R. Yates, III,⁷ Fotis C. Kafatos,⁹ Chris J. Janse,² Bart Barrell,¹ C. Michael R. Turner,⁸ Andrew P. Waters,^2* Robert E. Sinden^3*

Plasmodium berghei and Plasmodium chabaudi are widely used model malaria species. Comparison of their genomes, integrated with proteomic and microarray data, with the genomes of Plasmodium falciparum and Plasmodium yoelii revealed a conserved core of 4500 Plasmodium genes in the central regions of the 14 chromosomes and highlighted genes evolving rapidly because of stage-specific selective pressures. Four strategies for gene expression are apparent during the parasites' life cycle: (i) housekeeping; (ii) host-related; (iii) strategy-specific related to invasion, asexual replication, and sexual development; and (iv) stage-specific. We observed posttranscriptional gene silencing through translational repression of messenger RNA during sexual development, and a 47-base 3' untranslated region motif is implicated in this process.

¹ Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
² Department of Parasitology, Malaria Group, Leiden University Medical Center, Netherlands.
³ Immunology and Infection Section, Department of Biological Sciences, Imperial College London, Sir Alexander Fleming Building, Imperial College Road, London SW7 2AZ, UK.
⁴ The Institute for Genomic Research (TIGR), 9712 Medical Center Drive, Rockville, MD 20850, USA.
⁵ Department of Pathobiology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608, USA.
⁶ Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
⁷ Department of Cell Biology, The Scripps Research Institute, SR-11, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
⁸ Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
⁹ European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.
¹⁰ Naval Medical Research Center, Malaria Program (IDD), 503 Robert Grant Avenue, Room 3A40, Silver Spring, MD 20910–7500, USA.

These authors contributed equally to this work and are listed alphabetically. N.H. led the genome team; M.K., the transcriptome team; and J.D.R., the proteome team.

Present address: The Institute for Genomic Research, 9712 Medical Center Drive, Rockville, MD 20850, USA.

Present address: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.

^* To whom correspondence should be addressed. E-mail: nhall{at}tigr.org (N.H., genome), a.p.waters{at}lumc.nl (A.P.W., transcriptome), and r.sinden{at}imperial.ac.uk (R.E.S., proteome)