+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Identification of dosage-sensitive genes in Saccharomyces cerevisiae using the genetic tug-of-war method



Identification of dosage-sensitive genes in Saccharomyces cerevisiae using the genetic tug-of-war method



Genome Research 23(2): 300-311



Gene overexpression beyond a permissible limit causes defects in cellular functions. However, the permissible limits of most genes are unclear. Previously, we developed a genetic method designated genetic tug-of-war (gTOW) to measure the copy number limit of overexpression of a target gene. In the current study, we applied gTOW to the analysis of all protein-coding genes in the budding yeast Saccharomyces cerevisiae. We showed that the yeast cellular system was robust against an increase in the copy number by up to 100 copies in >80% of the genes. After frameshift and segmentation analyses, we isolated 115 dosage-sensitive genes (DSGs) with copy number limits of 10 or less. DSGs contained a significant number of genes involved in cytoskeletal organization and intracellular transport. DSGs tended to be highly expressed and to encode protein complex members. We demonstrated that the protein burden caused the dosage sensitivity of highly expressed genes using a gTOW experiment in which the open reading frame was replaced with GFP. Dosage sensitivities of some DSGs were rescued by the simultaneous increase in the copy numbers of partner genes, indicating that stoichiometric imbalances among complexes cause dosage sensitivity. The results obtained in this study will provide basic knowledge about the physiology of chromosomal abnormalities and the evolution of chromosomal composition.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036751554

Download citation: RISBibTeXText

PMID: 23275495

DOI: 10.1101/gr.146662.112


Related references

Heterozygous screen in Saccharomyces cerevisiae identifies dosage-sensitive genes that affect chromosome stability. Genetics 178(3): 1193-1207, 2008

Molecular analysis of Saccharomyces cerevisiae chromosome I. On the number of genes and the identification of essential genes using temperature-sensitive-lethal mutations. Journal of Molecular Biology 225(1): 53-65, 1992

Genetic mapping in saccharomyces cerevisiae part 4 mapping of temperature sensitive genes and use of disomic strains in localizing genes. Genetics 74(1): 35-54, 1973

Genetic analysis of Saccharomyces cerevisiae chromosome I: on the role of mutagen specificity in delimiting the set of genes identifiable using temperature-sensitive-lethal mutations. Genetics 127(2): 279-285, 1991

LA-PCR-based quick method for the identification of genes responsible for the complementation of Saccharomyces cerevisiae mutations. Biotechniques 20(5): 772, 1996

La-Pcr-Based Quick Method for the Identification of Genes Responsible for the Complementation of Saccharomyces cerevisiae Mutations. BioTechniques 20(5): 772-778, 1996

A rapid and sensitive non-radioactive method applicable for genome-wide analysis of Saccharomyces cerevisiae genes involved in small RNA biology. Yeast 30(4): 119-128, 2013

A genetic screen in Saccharomyces cerevisiae identifies new genes that interact with mex67-5, a temperature-sensitive allele of the gene encoding the mRNA export receptor. Molecular Genetics and Genomics 281(1): 125-134, 2009

Photoreactivation of saccharomyces cerevisiae cells after irradiation with 25 mev electrons the influence of the photoreactivable damage on the oxygen effect manifestation in radio sensitive and uv sensitive saccharomyces cerevisiae mutants. Radiobiologiya 26(4): 460-464, 1986

Gene dosage affects the expression of the duplicated NHP6 genes of Saccharomyces cerevisiae. Gene (Amsterdam) 272(1-2): 93-101, 11 July, 2001

Genetic differences between saccharomyces carlsbergensis and saccharomyces cerevisiae 2. restriction endo nuclease analysis of genes in chromosome iii. Carlsberg Research Communications 47(4): 233-244, 1982

Mapping chromosomal genes of Saccharomyces cerevisiae using an improved genetic mapping method. Genetics 92(3): 803-821, 1979

Genetic diversity study of the yeast Saccharomyces bayanus var. uvarum reveals introgressed subtelomeric Saccharomyces cerevisiae genes. Research in Microbiology 162(2): 204-213, 2011

Genes that cause overproduction of isoamyl alcohol by increased gene dosage effect in saccharomyces cerevisiae. Agricultural and Biological Chemistry 55(4): 919-924, 1991

Identification and genetic analysis of Saccharomyces pombe cDNA that suppress deletion of IRA1 in Saccharomyces cerevisiae. Gene 29(1): 147-152, 1993