Core Concepts
Natural yeast isolates exhibit widespread aneuploidy tolerance through protein turnover regulation, in contrast to the fitness costs observed in laboratory-generated aneuploids.
Abstract
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.
Stats
Around 20% of natural Saccharomyces cerevisiae isolates are aneuploid.
More than 70% of proteins encoded on aneuploid chromosomes in natural isolates are dosage compensated.
Quotes
"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."