Aneuploid Responses

A recent exchange of papers is divided over the evidence for compensatory gene expression among wild strains of aneuploid yeast.

Catherine Offord
Catherine Offord
Apr 30, 2016

DOSAGE DEBATE: Analyses of gene copy number in wild strains of aneuploid yeast (Saccharomyces cerevisiae) have come to different conclusions. © ISTOCK.COM/ALIENWORMZOND


The paper
A.P. Gasch et al., “Further support for aneuploidy tolerance in wild yeast and effects of dosage compensation on gene copy-number evolution,” eLife, 5:e14409, 2016.

Chromosomal commotion
Like many organisms, lab yeast (Saccharomyces cerevisiae) is intolerant of aneuploidy. “In the lab strain that’s been most studied, cells with an extra copy of a chromosome have just crazy different expression across the transcriptome,” says yeast researcher Audrey Gasch of the University of Wisconsin–Madison. But wild yeast, Gasch’s team recently found, may not be so sensitive.

Expressing differences
In 2015, Gasch and colleagues published an analysis comparing RNA levels and DNA content in aneuploid strains of wild yeast (eLife, 4:e05462). Doubling gene-copy number ought to double RNA abundance, the team reasoned, but some genes in these strains showed lower-than-expected gene expression, or “dosage compensation.”

Distribution dilemma
A reanalysis of Gasch’s data, published by yeast researcher Angelika Amon of MIT, revealed equal proportions of genes with higher- and lower-than-expected expression (eLife, 5:e10996, 2016). To conclude that dosage compensation is occurring, “there should be a departure from the one-to-one correlation between gene-copy number and expression levels” beyond the variation expected from statistical noise, says Amon. “When we looked at their data, there was no skewing. It was just a normal distribution, which is what you’d expect when gene expression doesn’t change.”

Opposing opinions
In its latest article, Gasch’s group argues that a distribution approach to dosage compensation may miss subtle differences in expression. “We’re thinking about it in different ways,” Gasch says. “I think this is of evolutionary importance, regardless of how many genes are subject to this effect.” She adds that the team will now investigate the mechanisms driving individual gene-expression differences between aneuploid strains of wild and lab yeast.