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

Date

2017

Authors

Bushell, Ellen
Gomes, Ana Rita
Sanderson, Theo
Anar, Burcu
Girling, Gareth
Herd, Colin
Metcalf, Tom
Modrzynska, Katarzyna
Schwach, Frank
Martin, Rowena

Journal Title

Journal ISSN

Volume Title

Publisher

Cell Press

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.

Description

Keywords

Citation

Source

Cell

Type

Journal article

Book Title

Entity type

Access Statement

Open Access

License Rights

CC BY license

DOI

10.1016/j.cell.2017.06.030

Restricted until