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Title: | Four layer multi-omics reveals molecular responses to aneuploidy in Leishmania | Data Creator - person: | 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 |
Data Creator - organization: | Institute of Tropical Medicine, Antwerp, Belgium University of Antwerp, Antwerp, Belgium |
Data Curator - person: | Cuypers, Bart | Data Curator - organization: | Institute of Tropical Medicine, Antwerp, Belgium University of Antwerp, Antwerp, Belgium |
Rights Holder - person: | Cuypers, Bart | Rights Holder - organization: | Institute of Tropical Medicine, Antwerp, Belgium University of Antwerp, Antwerp, Belgium |
Publisher: | PLOS Pathogens; Figshare | Issue Date: | 2022 | 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. | Research Discipline: | Medical and health sciences > Basic sciences > Microbiology > Parasitology (03012006) | Keywords: | Aneuploidy;Protein metabolism;Leishmania;Leishmania donovani;Genomics;Transcriptome analysis;Proteomes;Protein abundance | DOI: | 10.1371/journal.ppat.1010848.s001 10.1371/journal.ppat.1010848.s002 10.1371/journal.ppat.1010848.s003 10.1371/journal.ppat.1010848.s004 10.1371/journal.ppat.1010848.s005 10.1371/journal.ppat.1010848.s006 |
Source: | PLOS Pathogens; Figshare. 10.1371/journal.ppat.1010848.s001 10.1371/journal.ppat.1010848.s002 10.1371/journal.ppat.1010848.s003 10.1371/journal.ppat.1010848.s004 10.1371/journal.ppat.1010848.s005 10.1371/journal.ppat.1010848.s006 | Publications related to the dataset: | 10.1371/journal.ppat.1010848 | License: | Creative Commons Attribution 4.0 International (CC-BY-4.0) | Access Rights: | Open Access | Category: | DS | Type: | Dataset |
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