Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA280885 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aneuploidy has a myriad of consequences for health and disease, yet models of aneuploidy toxicity are still widely debated. To distinguish the effects of specific genes from the generalized burden of chromosome amplification, we measured the effects of duplicating individual genes in euploid cells as well as in select aneuploids using a barcoded plasmid library. We analyzed the responses of cells with and without extra chromosomes, as well as those with and without RNA-binding protein Ssd1. Deletion of Ssd1 sensitizes cells to chromosome amplification, but the source of this vulnerability is not known. Results of this experiment were used to interrogate determinants of aneuploidy toxicity, test models of Ssd1 dependence, and identify vulnerabilities of sensitized (ssd1-) and wild-type aneuploids. We also used the fitness effects of gene duplication in euploid cells to model the cost associated with chromosome duplication.
2024-05-01 | GSE263221 | GEO
Project description:Transcriptional consequences of aneuploidy
| PRJNA151875 | ENA
Project description:Aneuploidy is a hallmark of tumor cells and yet the precise relationship between aneuploidy and a cell’s proliferative ability, or cellular fitness, has remained elusive. In this study we have combined a detailed analysis of aneuploid clones isolated from laboratory-evolved populations of Saccharomyces cerevisiae with a systematic, genome-wide screen for the fitness effects of telomeric amplifications to address the relationship between aneuploidy and cellular fitness. We found that aneuploid clones rise to high population frequencies in nutrient-limited evolution experiments and show increased fitness relative to wild-type. Direct competition experiments confirmed that three out of four aneuploid events isolated from evolved populations were themselves sufficient to improve fitness. To expand the scope beyond this small number of exemplars, we created a genome-wide collection of >1,800 diploid yeast strains each containing a different telomeric amplicon (Tamp) ranging in size from 0.4 to 1,000kb. Using pooled competition experiments in nutrient-limited chemostats followed by high-throughput sequencing of strain-identifying barcodes, we determined the fitness effects of these >1,800 Tamps under three different conditions. Our data revealed that the fitness landscape explored by telomeric amplifications is much broader than that explored by single-gene amplifications. As also observed in the evolved clones, we found the fitness effects of most Tamps to be condition specific with a minority showing common effects in all three conditions. By integrating our data with previous work that examined the fitness effects of single-gene amplifications genome wide, we found that a small number of genes within each Tamp are centrally responsible for each Tamp’s fitness effects. Our genome-wide Tamp screen confirmed that telomeric amplifications identified in laboratory-evolved populations generally increased fitness. Our results show that Tamps are mutations that produce large, typically condition-dependent changes in fitness that are important drivers of increased fitness in asexually evolving populations. Each of these arrays is a Comparative Genomic Hybridization experiment to detect copy number differences between a reference strain and a strain of interest.
2015-04-12 | E-GEOD-67769 | biostudies-arrayexpress
Project description:Aneuploidy is a hallmark of tumor cells, and yet the precise relationship between aneuploidy and a cell’s proliferative ability, or cellular fitness, has remained elusive. In this study, we have combined a detailed analysis of aneuploid clones isolated from laboratory-evolved populations of Saccharomyces cerevisiae with a systematic, genome-wide screen for the fitness effects of telomeric amplifications to address the relationship between aneuploidy and cellular fitness. We found that aneuploid clones rise to high population frequencies in nutrient-limited evolution experiments and show increased fitness relative to wild type. Direct competition experiments confirmed that three out of four aneuploid events isolated from evolved populations were themselves sufficient to improve fitness. To expand the scope beyond this small number of exemplars, we created a genome-wide collection of >1,800 diploid yeast strains, each containing a different telomeric amplicon (Tamp), ranging in size from 0.4 to 1,000 kb. Using pooled competition experiments in nutrient-limited chemostats followed by high-throughput sequencing of strain-identifying barcodes, we determined the fitness effects of these >1,800 Tamps under three different conditions. Our data revealed that the fitness landscape explored by telomeric amplifications is much broader than that explored by single-gene amplifications. As also observed in the evolved clones, we found the fitness effects of most Tamps to be condition specific, with a minority showing common effects in all three conditions. By integrating our data with previous work that examined the fitness effects of single-gene amplifications genome-wide, we found that a small number of genes within each Tamp are centrally responsible for each Tamp’s fitness effects. Our genome-wide Tamp screen confirmed that telomeric amplifications identified in laboratory-evolved populations generally increased fitness. Our results show that Tamps are mutations that produce large, typically condition-dependent changes in fitness that are important drivers of increased fitness in asexually evolving populations.
2015-04-12 | GSE67769 | GEO
Project description:Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms.
2014-08-14 | PXD001019 | Pride
Project description:Massively parallel interrogation of the effects of gene expression levels on cellular fitness
| PRJNA329129 | ENA
Project description:Effects of aneuploidy on cellular physiology and cell division in haploid yeast.
| PRJNA100035 | ENA
Project description:Aneuploidy, the condition of having an abnormal number of chromosomes, is a hallmark of cancer cells. Recent work performed in yeast and mouse models suggests that aneuploidy interferes with cell proliferation and organism development. However, other recent experiments suggested that aneuploidy might play a positive role in tumor initiation and/or progression and in the emergence of chemotherapy as well as antibiotic resistances. Given its general deleterious effects on cellular fitness, how could aneuploidy be beneficial? In this set of experiments we plan to provide evidence that aneuploidy induces phenotypic variation through direct and indirect changes not only at the transcriptome but also at the proteome level.
2010-10-01 | E-MTAB-318 | biostudies-arrayexpress
Project description:Aneuploidy, the condition of having an abnormal number of chromosomes, is a hallmark of cancer cells. Recent work performed in yeast and mouse models suggests that aneuploidy interferes with cell proliferation and organism development. However, other recent experiments suggested that aneuploidy might play a positive role in tumor initiation and/or progression and in the emergence of chemotherapy as well as antibiotic resistances. Given its general deleterious effects on cellular fitness, how could aneuploidy be beneficial? In this set of experiments we plan to provide evidence that aneuploidy induces phenotypic variation through direct and indirect changes not only at the transcriptome but also at the proteome level.
2010-10-01 | E-MTAB-325 | biostudies-arrayexpress