Functional profiling of a Plasmodium genome reveals an abundance of essential genes

Bushell, E. et al. (2017) Functional profiling of a Plasmodium genome reveals an abundance of essential genes. Cell, 170(2), 260-272.e8. (doi: 10.1016/j.cell.2017.06.030) (PMID:28708996) (PMCID:PMC5509546)

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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.

Item Type:Articles
Additional Information:Work at the Sanger Institute was funded by a core grant from the Wellcome Trust (098051). R.E.M. is funded by the Australian National Health and Medical Research Council (fellowship 1053082) and the Australian Research Council (FT160100226).
Glasgow Author(s) Enlighten ID:Modrzynska, Dr Katarzyna
Authors: Bushell, E., Gomes, A. R., Sanderson, T., Anar, B., Girling, G., Herd, C., Metcalf, T., Modrzynska, K., Schwach, F., Martin, R. E., Mather, M. W., McFadden, G. I., Parts, L., Rutledge, G. G., Vaidya, A. B., Wengelnik, K., Rayner, J. C., and Billker, O.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Cell
ISSN (Online):1097-4172
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Cell 170(2):260-272.e8
Publisher Policy:Reproduced under a Creative Commons License

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