SRP310157 PRJNA713371 GSE168674 No evidence for whole-chromosome dosage compensation or global transcriptomic expression differences in spontaneously-aneuploid mutation accumulation lines of Saccharomyces cerevisiae Aneuploidy, the state in which an organism's genome contains one or more missing or additional chromosomes, often causes widespread genotypic and phenotypic effects. Most often, aneuploidies are deleterious; the most common examples in humans being Down's syndrome (Trisomy 21) and Turner's syndrome (monosomy X). However, aneuploidy is surprisingly common in wild yeast populations. In recent years, there has been debate as to whether yeast contain an innate dosage compensation response on the whole-genome level, or if these natural isolates are robust to aneuploidy without such a mechanism. In this study, we tested for differential gene expression in 20 aneuploid and 18 euploid lines of yeast from two previous mutation accumulation experiments, where selection was low and therefore aneuploidies arose spontaneously. We found no evidence for whole-chromosome dosage compensation in aneuploid yeast but did find some evidence for attenuation of expression on a gene-by-gene basis. We additionally found that aneuploidy has no effect on the expression of the rest of the genome (i.e. “trans” genes), and that very few mutually exclusive aneuploid lines shared differentially expressed genes. However, we found a small common differential expression response in the euploid lines, suggesting an effect of mutation accumulation on gene expression. Our findings contribute to our understanding of aneuploidy in yeast and support the hypothesis that there is no innate dosage compensation mechanism at the whole-chromosome level. Overall design: To determine the effects of aneuploidy on gene expression, we collected and analyzed RNA sequencing data from a selection of euploid and aneuploid lines from each experiment. For aneuploid samples, we chose all the MA lines that were monosomic for a chromosome (3 lines), those that shared common aneuploidies (21 lines), and those that had more than one aneuploidy event (4 lines). From the homozygous ancestor experiment, we selected 10 aneuploid and 12 euploid MA lines. From the heterozygous ancestor experiment, we selected 10 aneuploid and 6 euploid MA lines. Additionally, we collected RNA sequencing data for both ancestral lines. GSE168674