Scaling of cellular processes with ploidy

While most eukaryotic cells are diploid, with two chromosome sets, variances in ploidy are common. Despite the relative prevalence of ploidy changes and their relevance for pathology and evolution, a complete picture of consequences of altered ploidy is missing. We analyzed transcriptome and proteome changes in budding yeast Saccharomyces cerevisiae from haploid to tetraploid and found that the mRNA and protein abundance increases linearly with ploidy, but does not double with doubling the DNA content. Besides this linear increase, we found that pathways related to mitochondria and to cytoplasmic ribosomes and translation are differentially regulated. Indeed, with increasing ploidy the cells reduce mitochondrial content and this effect can be rescued by antioxidants. Moreover, cells of higher ploidy reduce their ribosome content while maintaining constant translational output. We show that this is an active process regulated via the Tor1 and Sch9 kinases and a transcriptional corepressor of rDNA transcription, Tup1. Similarly, human tetraploid cells downregulate their ribosome content via Tle1, a Tup1 homolog, demonstrating that the proteome remodeling is a conserved response to increased ploidy.