Supersaturation mutagenesis reveals adaptive rewiring of essential genes among malaria parasites

• 成果类型: Article
• 署名作者: Oberstaller, Jenna; Xu, Shulin; Naskar, Deboki; Zhang, Min; Wang, Chengqi; Gibbons, Justin; Pires, Camilla Valente; Mayho, Matthew; Otto, Thomas D.; Rayner, Julian C.; Adams, John H.
• 署名单位: State University System of Florida; University of South Florida; University of Cambridge; Wellcome Trust Sanger Institute; University of Glasgow; Universite de Montpellier; Centre National de la Recherche Scientifique (CNRS); Universite de Montpellier; Institut National de la Sante et de la Recherche Medicale (Inserm); Mahidol University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10540
• DOI: 10.1126/science.adq7347
• 发表日期: 2025-02-07
• 关键词: plasmodium-falciparum; transposon mutagenesis; fp-locus; genome; baculoviruses; insertions; knowlesi; annotation; expression; pathogen

摘要

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 Plasmodium knowlesi 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 Plasmodium species. Although gene essentiality was largely conserved across P. knowlesi, Plasmodium falciparum, and rodent malaria model Plasmodium berghei, a large number of shared genes are differentially essential, revealing species-specific adaptations. Our results indicated that Plasmodium essential gene evolution was conditionally linked to adaptive rewiring of metabolic networks for different hosts.