%0 Generic %A Tang, Yong %A Meister, Thomas R. %A Walczak, Marta %A Pulkoski-Gross, Michael J. %A Hari, Sanjay B. %A Sauer, Robert T. %A Amberg-Johnson, Katherine %A Yeh, Ellen %D 2019 %T A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites %U https://plos.figshare.com/articles/dataset/A_mutagenesis_screen_for_essential_plastid_biogenesis_genes_in_human_malaria_parasites/7681061 %R 10.1371/journal.pbio.3000136 %2 https://ndownloader.figshare.com/files/14284805 %2 https://ndownloader.figshare.com/files/14284808 %2 https://ndownloader.figshare.com/files/14284814 %2 https://ndownloader.figshare.com/files/14284817 %2 https://ndownloader.figshare.com/files/14284823 %2 https://ndownloader.figshare.com/files/14284826 %2 https://ndownloader.figshare.com/files/14284829 %2 https://ndownloader.figshare.com/files/14284832 %2 https://ndownloader.figshare.com/files/14284835 %2 https://ndownloader.figshare.com/files/14284838 %2 https://ndownloader.figshare.com/files/14284841 %2 https://ndownloader.figshare.com/files/14284844 %2 https://ndownloader.figshare.com/files/14284850 %2 https://ndownloader.figshare.com/files/14284853 %K malaria parasites Endosymbiosis %K TIM %K Plasmodium %K enzyme %K plastid biogenesis genes %K mutagenesis screen %K apicoplast biogenesis proteins %K falciparum %K organelle %X

Endosymbiosis has driven major molecular and cellular innovations. Plasmodium 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 Plasmodium falciparum. 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 P. falciparum 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.

%I PLOS Biology