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>