Abstract
In response to acute loss of the Ulp2 SUMO-specific protease, yeast become disomic for chromosome I (ChrI) and ChrXII. Here we report that ChrI disomy, which creates an adaptive advantage in part by increasing the dosage of the Ccr4 deadenylase, was eliminated by extended passaging. Loss of aneuploidy is often accompanied by mutations in essential SUMO-ligating enzymes, which reduced polySUMO-conjugate accumulation. The mRNA levels for almost all ribosomal proteins increase transiently upon initial loss of Ulp2, but elevated Ccr4 levels limit excess ribosome formation. Notably, extended passaging leads to increased levels of many small nucleolar RNAs (snoRNAs) involved in ribosome biogenesis, and higher dosage of three linked ChrXII snoRNA genes suppressed ChrXII disomy in ulp2Δ cells. Our data reveal that aneuploidy allows rapid adaptation to Ulp2 loss, but long-term adaptation restores euploidy. Cellular evolution restores homeostasis through countervailing mutations in SUMO-modification pathways and regulatory shifts in ribosome biogenesis.
Highlights
In response to acute loss of the Ulp[2] small ubiquitin-like modifier (SUMO)-specific protease, yeast become disomic for chromosome I (ChrI) and ChrXII
ChrI disomy of ulp2Δ cells is lost after extended culture
We first explored how quickly aneuploidy is established. For this we developed an improved inducible AID* degron-tagged ULP2 construct in which the degradation of the mRNA can be induced through a neomycin-regulated self-cleaving hammerhead ribozyme in the 3′-UTR (Supplementary Fig. 1)
Summary
In response to acute loss of the Ulp[2] SUMO-specific protease, yeast become disomic for chromosome I (ChrI) and ChrXII. Acute changes in the local microenvironment, such as changes of pH or temperature, oxidative stress, or nutrient limitation, may induce programmed cell death or trigger adaptive changes that include gene mutation, aneuploidy, changes in gene expression or epigenetic alterations[3,4,5]. Adaptations often involve genomic sequence polymorphisms, including single-nucleotide variations, insertions, deletions, and other structural variations, as well as large copy number variants and aneuploidy[10,11,12]. Such studies revealed that many genome modifications contribute to species diversification, evolution, and adaptation[4,13,14]. Its loss results in a pleiotropic mutant phenotype including defects in cell growth; sensitivity to heat, DNA damage or aberrant spindle formation; and high rates of chromosome and plasmid loss[17]
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