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Title: | Four layer multi-omics reveals molecular responses to aneuploidy in Leishmania | Authors: | Cuypers, Bart Meysman, Pieter Erb, Ionas Bittremieux, Wout VALKENBORG, Dirk Baggerman, Geert Mertens, Inge Sundar, Shyam Khanal, Basudha Notredame, Cedric Dujardin, Jean-Claude Domagalska, Malgorzata A. Laukens, Kris |
Editors: | Engwerda, Christian R. | Issue Date: | 2022 | Publisher: | PUBLIC LIBRARY SCIENCE | Source: | PLoS Pathogens, 18 (9) (Art N° e1010848) | Abstract: | Aneuploidy causes system-wide disruptions in the stochiometric balances of transcripts, proteins, and metabolites, often resulting in detrimental effects for the organism. The protozoan parasite Leishmania has an unusually high tolerance for aneuploidy, but the molecular and functional consequences for the pathogen remain poorly understood. Here, we addressed this question in vitro and present the first integrated analysis of the genome, transcriptome, proteome, and metabolome of highly aneuploid Leishmania donovani strains. Our analyses unambiguously establish that aneuploidy in Leishmania proportionally impacts the average transcript- and protein abundance levels of affected chromosomes, ultimately correlating with the degree of metabolic differences between closely related aneuploid strains. This proportionality was present in both proliferative and non-proliferative in vitro promastigotes. However, as in other Eukaryotes, we observed attenuation of dosage effects for protein complex subunits and in addition, non-cytoplasmic proteins. Differentially expressed transcripts and proteins between aneuploid Leishmania strains also originated from non-aneuploid chromosomes. At protein level, these were enriched for proteins involved in protein metabolism, such as chaperones and chaperonins, peptidases, and heat-shock proteins. In conclusion, our results further support the view that aneuploidy in Leishmania can be adaptive. Additionally, we believe that the high karyotype diversity in vitro and absence of classical transcriptional regulation make Leishmania an attractive model to study processes of protein homeostasis in the context of aneuploidy and beyond. | Notes: | Dujardin, JC; Domagalska, MA (corresponding author), Inst Trop Med, Dept Biomed Sci, Mol Parasitol Unit, Antwerp, Belgium.; Laukens, K (corresponding author), Univ Antwerp, Dept Comp Sci, Adrem Data Lab, Antwerp, Belgium.; Dujardin, JC (corresponding author), Univ Antwerp, Dept Biomed Sci, Antwerp, Belgium. jcdujardin@itg.be; mdomagalska@itg.be; kris.laukens@uantwerpen.be |
Keywords: | Aneuploidy;Heat-Shock Proteins;Humans;Karyotype;Peptide Hydrolases;Leishmania donovani;Proteome | Document URI: | http://hdl.handle.net/1942/39692 | ISSN: | 1553-7366 | e-ISSN: | 1553-7374 | DOI: | 10.1371/journal.ppat.1010848 | ISI #: | 000933390100001 | Rights: | 2022 Cuypers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
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Four layer multi-omics reveals molecular responses to aneuploidy in Leishmania.pdf | Published version | 2.67 MB | Adobe PDF | View/Open |
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