Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes

Ellen Bushell, Ana Rita Gomes, Theo Sanderson, Burcu Anar, Gareth Girling, Colin Herd, Tom Metcalf, Katarzyna Modrzynska, Frank Schwach, Rowena E. Martin, Michael W. Mather, Geoffrey I. McFadden, Leopold Parts, Gavin G. Rutledge, Akhil B. Vaidya, Kai Wengelnik, Julian C. Rayner*, Oliver Billker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

219 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)260-272.e8
JournalCell
Volume170
Issue number2
DOIs
Publication statusPublished - 13 Jul 2017
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Mandy Sanders for handling sequencing samples, Thomas Dibling and Anthea Cassidy for picking and managing the genomic clone resource, and Wieslawa Johnson and Francois Meullenet for help with manuscript preparation. 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).

Publisher Copyright:
© 2017 The Authors

Keywords

  • cancer immunology
  • cancer inflammation
  • carcinoma-associated fibroblast (CAF)
  • dendritic cells
  • interferon
  • lncRNA
  • myeloid cells
  • radiation resistance
  • triple negative breast cancer
  • tumor microenvironment

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