A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites
Author(s)Hari, Sanjay B.; Sauer, Rober T.
MetadataShow full item record
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.
DepartmentMassachusetts Institute of Technology. Department of Biology
Public Library of Science (PLoS)
Tang, Yong et al. "A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites." PloS one 17 (2019): journal.pbio.3000136 © 2019 The Author(s)
Final published version
General Biochemistry, Genetics and Molecular Biology, General Immunology and Microbiology, General Neuroscience, General Agricultural and Biological Sciences