Supersaturation mutagenesis reveals adaptive rewiring of essential genes among malaria parasites
Malaria parasites are highly divergent from model eukaryotes. Large-scale genome engineering methods effective in model organisms are frequently inapplicable, and systematic studies of gene function are few. We generated more than 175,000 transposon insertions in the <i>Plasmodium knowlesi</i> genome, averaging an insertion every 138 base pairs, and used this "supersaturation" mutagenesis to score essentiality for 98% of genes. The density of mutations allowed mapping of putative essential domains within genes, providing a completely new level of genome annotation for any <i>Plasmodium</i> species. Although gene essentiality was largely conserved across <i>P. knowlesi</i>, <i>Plasmodium falciparum</i>, and rodent malaria model <i>Plasmodium berghei</i>, a large number of shared genes are differentially essential, revealing species-specific adaptations. Our results indicated that <i>Plasmodium</i> essential gene evolution was conditionally linked to adaptive rewiring of metabolic networks for different hosts.
Authors
- Jenna Oberstaller (ORCID: https://orcid.org/0000-0002-3033-2212)
- Thomas D. Otto (ORCID: https://orcid.org/0000-0002-1246-7404)
- Deboki Naskar (ORCID: https://orcid.org/0000-0003-0902-3869)
- Justin Gibbons (ORCID: https://orcid.org/0000-0001-7156-6704)
- John H. Adams (ORCID: https://orcid.org/0000-0003-3707-7979)
- Julian C. Rayner (ORCID: https://orcid.org/0000-0002-9835-1014)
- Matthew Mayho (ORCID: https://orcid.org/0000-0002-7731-4820)
- Camilla Valente Pires (ORCID: https://orcid.org/0000-0002-5470-1342)
- Chengqi Wang (ORCID: https://orcid.org/0000-0002-7582-3824)
- Min Zhang (ORCID: https://orcid.org/0000-0002-5443-0992)
- Shulin Xu
Institutions
- University of Cambridge (GB)
- Mahidol University (TH)
- University of South Florida (US)
- Wellcome Sanger Institute (GB)
- Centre National pour la Recherche Scientifique et Technique (CNRST) (MA)
- Mahidol Oxford Tropical Medicine Research Unit (TH)
- University of Glasgow (GB)
Publication Details
- Journal
- Science
- Published
- 2025-02-06
- DOI
- https://doi.org/10.1126/science.adq7347
- Citations
- 14
- Primary Topic
- Malaria Research and Control
- Type
- article
- Field-Weighted Citation Impact
- 26.30
Funders
- Wellcome Trust
- Université de Montpellier
- National Institutes of Health