Dosage compensation can buffer copy - number variation in wild yeast 1 2

IMPACT STATEMENT: Our results suggest that dosage-compensated gene expression 19 facilitates chromosomal aneuploidy, which presents a rapid route to phenotypic evolution 20 in natural yeast isolates. ABSTRACT 23 Aneuploidy is linked to myriad diseases but also facilitates organismal evolution. It remains unclear how cells overcome the deleterious effects of aneuploidy until 25 new phenotypes evolve. Although laboratory strains are extremely sensitive to 26 aneuploidy, we show here that aneuploidy is common in wild yeast isolates, which 27 show lower-than-expected expression at many amplified genes. We generated 28 diploid strain panels in which cells carried two, three, or four copies of the 29 affected chromosomes, to show that gene dosage compensation functions at 30 >30% of amplified genes. Genes subject to dosage compensation are under 31 higher expression constraint in wild populations – but they show elevated rates of 32 gene amplification, suggesting that copy number variation is buffered at these 33 genes. We find that aneuploidy provides a clear ecological advantage to oak 34 strain YPS1009, by amplifying a causal gene that escapes dosage compensation. 36 amplification through aneuploidy to provide a natural, but likely transient, route to 37 rapid phenotypic evolution.