title: A general lack of compensation for gene dosage in yeast.
abstract: Gene copy number variation has been discovered in humans, between related species, and in different cancer tissues, but it is unclear how much of this genomic-level variation leads to changes in the level of protein abundance. To address this, we eliminated one of the two genomic copies of 730 different genes in Saccharomyces cerevisiae and asked how often a 50% reduction in gene dosage leads to a 50% reduction in protein level. For at least 80% of genes tested, and under several environmental conditions, it does: protein levels in the heterozygous strain are close to 50% of wild type. For <5% of the genes tested, the protein levels in the heterozygote are maintained at nearly wild-type levels. These experiments show that protein levels are not, in general, directly monitored and adjusted to a desired level. Combined with fitness data, this implies that proteins are expressed at levels higher than necessary for survival.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Springer
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Weissman
authors.forename: Marc W
authors.initials: MW
authors.lastname: Kirschner
mesh_terms: D025461:Feedback, Physiological; D018628:Gene Dosage; D005800:Genes, Fungal; D023281:Genomics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
chemical_list: D029701:Saccharomyces cerevisiae Proteins
references.citation: Cell. 1982 Jun;29(2):347-55
references.pmid: 7116444
references.citation: Nature. 2003 Oct 16;425(6959):686-91
references.pmid: 14562095
references.citation: Mol Gen Genet. 1977 Dec 9;157(3):327-32
references.pmid: 340929
references.citation: Nature. 2003 Oct 16;425(6959):737-41
references.pmid: 14562106
references.citation: PLoS One. 2007 Feb 28;2(2):e250
references.pmid: 17327914
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: Nat Cell Biol. 2007 Apr;9(4):422-7
references.pmid: 17310239
references.citation: Genetics. 1972 May;71(1):157-84
references.pmid: 4624779
references.citation: Genome Biol. 2003;4(4):R28
references.pmid: 12702209
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12963-8
references.pmid: 12297621
references.citation: Genome Res. 2007 Sep;17(9):1266-77
references.pmid: 17666543
references.citation: Science. 1999 Aug 6;285(5429):901-6
references.pmid: 10436161
references.citation: Science. 2007 Aug 17;317(5840):916-24
references.pmid: 17702937
references.citation: Nature. 2006 Jun 15;441(7095):840-6
references.pmid: 16699522
references.citation: Genetics. 2008 Mar;178(3):1653-60
references.pmid: 18245823
references.citation: Science. 2008 Apr 18;320(5874):362-5
references.pmid: 18420932
references.citation: Nat Methods. 2008 Aug;5(8):711-8
references.pmid: 18622397
references.citation: Cell. 1981 Aug;25(2):537-46
references.pmid: 6116546
references.citation: RNA. 2002 Aug;8(8):969-80
references.pmid: 12212852
references.citation: Nat Genet. 2000 Jul;25(3):333-7
references.pmid: 10888885
references.citation: Mol Cell. 2006 Feb 3;21(3):319-30
references.pmid: 16455487
references.citation: Nature. 2008 May 1;453(7191):56-64
references.pmid: 18451855
references.citation: J Clin Invest. 2002 Feb;109(4):451-5
references.pmid: 11854316
references.citation: Genetics. 1981 Mar-Apr;97(3-4):639-66
references.pmid: 7297851
references.citation: Genetics. 2005 Apr;169(4):1915-25
references.pmid: 15716499
references.citation: Nat Genet. 1999 Mar;21(3):278-83
references.pmid: 10080179
references.citation: Nature. 2005 Jul 28;436(7050):588-92
references.pmid: 16049495
references.citation: Cell. 2004 Jul 9;118(1):31-44
references.pmid: 15242642
references.citation: Genes Dev. 2005 Dec 1;19(23):2816-26
references.pmid: 16322557
references.citation: Nucleic Acids Res. 2008 Jan;36(Database issue):D637-40
references.pmid: 18000002