dc.contributor.author | Hari, Sanjay B. | |
dc.contributor.author | Sauer, Rober T. | |
dc.date.accessioned | 2020-04-08T11:33:56Z | |
dc.date.available | 2020-04-08T11:33:56Z | |
dc.date.issued | 2019-02-06 | |
dc.identifier.issn | 1545-7885 | |
dc.identifier.uri | https://hdl.handle.net/1721.1/124521 | |
dc.description.abstract | 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. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.). Department of Health and Human Services (Award AI016892) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.). Department of Health and Human Services (Award F32GM116241) | en_US |
dc.language.iso | en | |
dc.publisher | Public Library of Science (PLoS) | en_US |
dc.relation.isversionof | 10.1371/journal.pbio.3000136 | en_US |
dc.rights | Creative Commons Attribution 4.0 International license | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.source | PLoS | en_US |
dc.subject | General Biochemistry, Genetics and Molecular Biology | en_US |
dc.subject | General Immunology and Microbiology | en_US |
dc.subject | General Neuroscience | en_US |
dc.subject | General Agricultural and Biological Sciences | en_US |
dc.title | A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites | en_US |
dc.type | Article | en_US |
dc.identifier.citation | 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) | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.relation.journal | PloS one | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dc.date.updated | 2020-01-30T17:31:28Z | |
dspace.date.submission | 2020-01-30T17:31:29Z | |
mit.journal.volume | 17 | en_US |
mit.journal.issue | 2 | en_US |
mit.license | PUBLISHER_CC | |
mit.metadata.status | Complete | |