Further support for aneuploidy tolerance in wild yeast and effects of dosage compensation on gene copy-number evolution
- University of Wisconsin-Madison, United States
Abstract
In Hose et al., we performed a genome-sequencing survey and reported that aneuploidy was frequently observed in wild strains of S. cerevisiae. We also profiled transcriptome abundance in naturally aneuploid isolates and found that 10-30% of amplified genes, depending on the strain and affected chromosome, show lower-than-expected expression compared to gene copy number. We argued that this gene group is enriched for genes subject to one or more modes of dosage compensation, where mRNA abundance is decreased in response to higher dosage of that gene. A recent manuscript by Torres et al. refutes our prior work. Here we provide a response to Torres et al., along with additional analysis and controls to support our original conclusions. We maintain that aneuploidy is well tolerated in the wild strains of S. cerevisiae that we studied and that the group of genes enriched for those subject to dosage compensation show unique evolutionary signatures.
Article and author information
Author details
Reviewing Editor
- Duncan T Odom, University of Cambridge, United Kingdom
Version history
- Received: January 14, 2016
- Accepted: February 26, 2016
- Accepted Manuscript published: March 7, 2016 (version 1)
- Version of Record published: March 9, 2016 (version 2)
Copyright
© 2016, Gasch et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Further support for aneuploidy tolerance in wild yeast and effects of dosage compensation on gene copy-number evolution
eLife 5:e14409.
https://doi.org/10.7554/eLife.14409
Further reading
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- Chromosomes and Gene Expression
- Genetics and Genomics
Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until new phenotypes evolve. Although laboratory strains are extremely sensitive to aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which show lower-than-expected expression at many amplified genes. We generated diploid strain panels in which cells carried two, three, or four copies of the affected chromosomes, to show that gene-dosage compensation functions at 10–30% of amplified genes. Genes subject to dosage compensation are under higher expression constraint in wild populations—but they show elevated rates of gene amplification, suggesting that copy-number variation is buffered at these genes. We find that aneuploidy provides a clear ecological advantage to oak strain YPS1009, by amplifying a causal gene that escapes dosage compensation. Our work presents a model in which dosage compensation buffers gene amplification through aneuploidy to provide a natural, but likely transient, route to rapid phenotypic evolution.
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- Computational and Systems Biology
Transcriptomic profiling became a standard approach to quantify a cell state, which led to accumulation of huge amount of public gene expression datasets. However, both reuse of these datasets or analysis of newly generated ones requires significant technical expertise. Here we present Phantasus - a user-friendly web-application for interactive gene expression analysis which provides a streamlined access to more than 96000 public gene expression datasets, as well as allows analysis of user-uploaded datasets. Phantasus integrates an intuitive and highly interactive JavaScript-based heatmap interface with an ability to run sophisticated R-based analysis methods. Overall Phantasus allows users to go all the way from loading, normalizing and filtering data to doing differential gene expression and downstream analysis. Phantasus can be accessed on-line at https://alserglab.wustl.edu/phantasus or can be installed locally from Bioconductor (https://bioconductor.org/packages/phantasus). Phantasus source code is available at https://github.com/ctlab/phantasus under MIT license.
