Proteomics

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The natural diversity of the yeast proteome links aneuploidy tolerance to genome-wide proteome


ABSTRACT: Recent advancements in genome sequencing have facilitated accessing the natural genetic diversity of species, unveiling hidden genetic traits, clarifying gene functions, and the degree to which laboratory studies can be generalized. One notable discovery is the frequent (~20%) aneuploidy - an imbalance in chromosome copy numbers - in natural Saccharomyces cerevisiae (Sc) isolates, despite the significant fitness costs and transient nature reported for lab-engineered yeast aneuploids. To examine this discrepancy, we adapted a high-throughput proteomic platform to analyze the proteome of 800 diverse yeast isolates. Matching these proteomes to the natural isolates’ genomes, transcriptomes, as well as generating ubiquitinome and protein turnover data for selected isolates, we report that natural and lab-generated aneuploids differ specifically at the proteome. While lab-generated aneuploids attenuate specific proteins – mostly protein complex subunits – and do not alter the average gene dosage provided by chromosome duplications, in natural strains, 70% of proteins encoded on aneuploid chromosomes are attenuated, and protein levels are shifted towards the euploid state chromosome-wide. Our data links chromosome-wide dosage compensation in natural strains to i) genome-wide buffering of gene expression changes manifesting in trans on euploid chromosomes, ii) increased expression of structural components of the ubiquitin proteasome system, and iii) increased global rates of protein turnover. Our results encourage the exploitation of natural diversity of species to understand complex biological processes at the molecular level. This submission contains the raw files for the disomics lab engineered strains, the library used for the analysis and the corresponding DIA-NN report and associated files.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Anja Freiwald  

LAB HEAD: Markus Ralser

PROVIDER: PXD044526 | Pride | 2024-03-11

REPOSITORIES: Pride

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Publications


Accessing the natural genetic diversity of species unveils hidden genetic traits, clarifies gene functions and allows the generalizability of laboratory findings to be assessed. One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy-an imbalance in chromosome copy numbers-is frequent<sup>1,2</sup> (around 20%), which seems to contradict the substantial fitness costs and transient nature of aneuploidy when it is engineered in the laboratory<sup>3-5</sup>. He  ...[more]

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