Dosage compensation can buffer copy-number variation in wild yeast

We show that aneuploidy is common in wild isolates of yeast, which are inherently tolerant to chromosome amplification and down-regulate expression at 40% of amplified genes.  To dissect the mechanism of this dosage response, we generated isogenic strain panels in which diploid cells carried either two, three, or four copies of the affected chromosomes.  Using a mixture of linear regression (MLR) model to classify genes, we find that expression is actively down regulated in proportion to increased gene copy at up to 30% of genes. Genes subject to dosage control are under higher expression constraint – but show elevated rates of gene amplification – in wild populations, suggesting that dosage compensation buffers copy number variation (CNV) at toxic genes RNA-seq and transcriptome analysis of S. cerevisiae natural isolates having aneuploidy. Technical triplicate was performed for isogenic diploid strains having 2, 3 and 4 copies of a given chromosome (strain panels), while technical duplicate or singulate was performed on all other aneuploids.