Proteome Diversity Enables Aneuploidy Tolerance in Natural Yeast Isolates

Konsep Inti

Natural yeast isolates exhibit widespread aneuploidy tolerance through protein turnover regulation, in contrast to the fitness costs observed in laboratory-generated aneuploids.

Abstrak

The article explores the natural genetic diversity of Saccharomyces cerevisiae (baker's yeast) and its link to aneuploidy tolerance. Aneuploidy, an imbalance in chromosome copy numbers, is surprisingly common in natural yeast isolates (around 20%), despite the substantial fitness costs observed in laboratory-generated aneuploids.
The researchers generated a proteomic resource by merging genomic and transcriptomic data for 796 euploid and aneuploid natural yeast isolates. They found that natural and lab-generated aneuploids differ significantly at the proteome level. In lab-generated aneuploids, some proteins (especially subunits of protein complexes) show reduced expression, with overall protein levels corresponding to the aneuploid gene dosage.
In contrast, in natural yeast isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, and average protein levels are shifted towards the euploid state chromosome-wide. At the molecular level, the researchers detected an induction of structural components of the proteasome, increased levels of ubiquitination, and an interdependency of protein turnover rates and attenuation.
These findings highlight the role of protein turnover regulation in mediating aneuploidy tolerance in natural yeast isolates, in contrast to the fitness costs observed in laboratory-generated aneuploids. The study demonstrates the utility of exploiting natural genetic diversity to gain generalizable insights into complex biological processes.

Statistik

Around 20% of natural Saccharomyces cerevisiae isolates are aneuploid.
More than 70% of proteins encoded on aneuploid chromosomes in natural isolates are dosage compensated.

Kutipan

"One notable discovery made in natural isolates of Saccharomyces cerevisiae is that aneuploidy—an imbalance in chromosome copy numbers—is frequent1,2 (around 20%), which seems to contradict the substantial fitness costs and transient nature of aneuploidy when it is engineered in the laboratory3,4,5."
"By contrast, in natural isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, and average protein levels are shifted towards the euploid state chromosome-wide."

Wawasan Utama Disaring Dari

Natural proteome diversity links aneuploidy tolerance to protein turnover - Nature

by Juli... pada www.nature.com 05-22-2024

https://www.nature.com/articles/s41586-024-07442-9

Pertanyaan yang Lebih Dalam

What are the specific mechanisms underlying the protein turnover regulation that enables aneuploidy tolerance in natural yeast isolates?

The study reveals that in natural yeast isolates, more than 70% of proteins encoded on aneuploid chromosomes are dosage compensated, leading to average protein levels being shifted towards the euploid state chromosome-wide. This compensation mechanism involves an induction of structural components of the proteasome, increased levels of ubiquitination, and an interdependency of protein turnover rates and attenuation. Essentially, the natural yeast isolates exhibit a robust protein turnover system that helps maintain protein levels despite aneuploidy, thereby enabling aneuploidy tolerance.

How do the findings in this study on aneuploidy tolerance in yeast compare to observations in other eukaryotic organisms, such as human cells?

The findings in this study shed light on the unique protein turnover mechanisms that underlie aneuploidy tolerance in yeast. While direct comparisons to human cells may require further research, some parallels can be drawn. For instance, the concept of dosage compensation and protein turnover regulation in response to aneuploidy could potentially be conserved across eukaryotic organisms. However, the specific molecular pathways and regulatory networks involved may vary between yeast and human cells. Further studies in human cells are needed to determine the extent of similarity or divergence in the mechanisms of aneuploidy tolerance.

What potential applications or implications could the insights from this study have for understanding and addressing aneuploidy-related diseases or disorders in humans?

The insights from this study offer valuable information on the role of protein turnover in mediating aneuploidy tolerance, which could have significant implications for understanding and addressing aneuploidy-related diseases or disorders in humans. By elucidating the mechanisms by which natural yeast isolates tolerate aneuploidy, researchers may gain insights into potential therapeutic targets or strategies for managing aneuploidy-related conditions in humans. Understanding how protein turnover is involved in maintaining cellular homeostasis despite aneuploidy could pave the way for developing targeted interventions to mitigate the adverse effects of aneuploidy in human cells, potentially leading to novel treatment approaches for aneuploidy-related diseases.