A mutagenesis screen for essential plastid biogenesis genes in human malaria parasites
Name
journal.pbio.3000136.pdf
Description
Published version
Size
2.93 MB
Format
Adobe PDF
Checksum (MD5)
9500489441068932922ac78e37280919
Author(s)
Hari, Sanjay B.
Sauer, Rober T.
Date Issued
February 6, 2019
Journal
PloS one
Publisher
Public Library of Science (PLoS)
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)
Version
Final published version
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.
Subjects
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
General Neuroscience
General Agricultural and Biological Sciences
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pbio.3000136
