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Scaling of cellular processes with ploidy

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

TISSUE(S): Cell Culture

SUBMITTER: Paul Menges

LAB HEAD: Prof. Dr. Zuzana Storchova

PROVIDER: PXD022605 | Pride | 2022-08-15

REPOSITORIES: Pride

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			Action	DRS
	20130719_EXQ2_NiKu_SA_Yeast_Ploidy1_01.raw	Raw
	20130719_EXQ2_NiKu_SA_Yeast_Ploidy1_02.raw	Raw
	20130719_EXQ2_NiKu_SA_Yeast_Ploidy1_03.raw	Raw
	20130719_EXQ2_NiKu_SA_Yeast_Ploidy2_01.raw	Raw
	20130719_EXQ2_NiKu_SA_Yeast_Ploidy2_02.raw	Raw

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Scaling of cellular gene expression with ploidy

Project description:Whereas most eukaryotic cells are diploid, carrying two chromosome sets, variances in ploidy are common. Despite the relative prevalence of ploidy changes and their relevance for pathology and evolution, the consequences of altered ploidy for cellular gene expression remain poorly understood. We quantified changes in the transcriptome and proteome of the yeast Saccharomyces cerevisiae with different ploidy, from the haploid to the tetraploid state. We found that the abundance of proteins increases with ploidy, but does not scale proportionally with increasing DNA content, suggesting a compensatory, cellular response to increases in ploidy. We further found that pathways related to cytoplasmic ribosomes and translation are differentially regulated. With increasing ploidy the cells reduced the rRNA and ribosomal protein abundance, although they maintained a constant translational output. These adaptations stem from an active process that involves the kinases Tor1 and Sch9 and the transcriptional corepressor of rDNA transcription, Tup1. Consistent with our results in yeast, human tetraploid cells show reduced mTORC1 activity and downregulated their ribosome content via the Tup1 homolog Tle1, demonstrating that the proteome remodeling pathway discovered here constitutes a conserved response pathway to increased ploidy.

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Project description:Heterosis and polyploidy are two important aspects of plant evolution. To examine these issues, we conducted a global gene expression study of a maize ploidy series as well as a set of tetraploid inbred and hybrid lines. This gene expression analysis complements an earlier phenotypic study of these same materials. We find that ploidy change affects a large fraction of the genome, albeit at low levels; gene expression changes rarely exceed 2-fold and are typically not statistically significant. The most common gene expression profile we detected is greater than linear increase from monoploid to diploid, and reductions from diploid to triploid and from triploid to tetraploid, a trend that mirrors plant stature. When examining heterosis in tetraploid maize lines, we found a large fraction of the genome impacted but the majority of changes were not statistically significant at 2-fold or less. Non-additive expression was common in the hybrids, and the extent of non-additivity increased both in number and magnitude from duplex to quadruplex hybrids. Overall, we find that gene expression trends mirror observations from the phenotypic studies; however, obvious mechanistic connections remain unknown. We examined gene expression in a ploidy series (1n to 4n) of the maize line B73 and in a variety of hybrid tetraploid lines using a complex loop design. Pooled RNA samples from 10 plants were used (2 independent RNA isolations/sample), and all comparisons were made using replicate dye swaps (16 slide sets/comparison). For the ploidy analysis, all expression changes were computed relative to the diploid as well as between 2n + 3n and 3n + 4n. For the expression analysis of hybrids, hybrid expression levels were compared to the parental expression levels as well as to mid-parent levels.

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