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Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes
Cell, v 170(2), pp 260-272
13 Jul 2017
PMID: 28708996
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded Plasmodium berghei knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, P. berghei requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probable consequence of functional optimization necessitated by genomic reductions during the evolution of parasitism. In contrast, extreme functional redundancy has evolved among expanded gene families operating at the parasite-host interface. The level of genetic redundancy in a single-celled organism may thus reflect the degree of environmental variation it experiences. In the case of Plasmodium parasites, this helps rationalize both the relative successes of drugs and the greater difficulty of making an effective vaccine.
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Details
- Title
- Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes
- Creators
- Ellen Bushell - Wellcome Sanger InstituteAna Rita Gomes - Wellcome Sanger InstituteTheo Sanderson - Wellcome Sanger InstituteBurcu Anar - Wellcome Sanger InstituteGareth Girling - Wellcome Sanger InstituteColin Herd - Wellcome Sanger InstituteTom Metcalf - Wellcome Sanger InstituteKatarzyna Modrzynska - Wellcome Sanger InstituteFrank Schwach - Wellcome Sanger InstituteRowena E. Martin - Australian National UniversityMichael W. Mather - Drexel UniversityGeoffrey I. McFadden - University of MelbourneLeopold Parts - Wellcome Sanger InstituteGavin G. Rutledge - Wellcome Sanger InstituteAkhil B. Vaidya - Drexel UniversityKai Wengelnik - University of MontpellierJulian C. Rayner - Wellcome Sanger InstituteOliver Billker - Wellcome Sanger Institute
- Publication Details
- Cell, v 170(2), pp 260-272
- Publisher
- Elsevier
- Number of pages
- 21
- Grant note
- 1500002 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); European Commission G0501670 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 098051 / Wellcome Trust; European Commission R01AI028398; R56AI028398 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) FT160100226 / Australian Research Council 1053082 / Australian National Health and Medical Research Council; National Health and Medical Research Council (NHMRC) of Australia
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000405493900007
- Scopus ID
- 2-s2.0-85023618715
- Other Identifier
- 991019168828104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology