10.1371/journal.pbio.3000136 Yong Tang Yong Tang Thomas R. Meister Thomas R. Meister Marta Walczak Marta Walczak Michael J. Pulkoski-Gross Michael J. Pulkoski-Gross Sanjay B. Hari Sanjay B. Hari Robert T. Sauer Robert T. Sauer Katherine Amberg-Johnson Katherine Amberg-Johnson Ellen Yeh Ellen Yeh A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites Public Library of Science 2019 malaria parasites Endosymbiosis TIM Plasmodium enzyme plastid biogenesis genes mutagenesis screen apicoplast biogenesis proteins falciparum organelle 2019-02-06 18:25:53 Dataset https://plos.figshare.com/articles/dataset/A_mutagenesis_screen_for_essential_plastid_biogenesis_genes_in_human_malaria_parasites/7681061 <div><p>Endosymbiosis has driven major molecular and cellular innovations. <i>Plasmodium</i> spp. parasites that cause malaria contain an essential, non-photosynthetic plastid—the apicoplast—which originated from a secondary (eukaryote–eukaryote) endosymbiosis. To discover organellar pathways with evolutionary and biomedical significance, we performed a mutagenesis screen for essential genes required for apicoplast biogenesis in <i>Plasmodium falciparum</i>. Apicoplast(−) mutants were isolated using a chemical rescue that permits conditional disruption of the apicoplast and a new fluorescent reporter for organelle loss. Five candidate genes were validated (out of 12 identified), including a triosephosphate isomerase (TIM)-barrel protein that likely derived from a core metabolic enzyme but evolved a new activity. Our results demonstrate, to our knowledge, the first forward genetic screen to assign essential cellular functions to unannotated <i>P</i>. <i>falciparum</i> genes. A putative TIM-barrel enzyme and other newly identified apicoplast biogenesis proteins open opportunities to discover new mechanisms of organelle biogenesis, molecular evolution underlying eukaryotic diversity, and drug targets against multiple parasitic diseases.</p></div>