A general lack of compensation for gene dosage in yeast.
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.
Springer
Michael
M
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
Weissman
Jonathan S
JS
Kirschner
Marc W
MW
D025461:Feedback, Physiological; D018628:Gene Dosage; D005800:Genes, Fungal; D023281:Genomics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics
D029701:Saccharomyces cerevisiae Proteins
Cell. 1982 Jun;29(2):347-55
7116444
Nature. 2003 Oct 16;425(6959):686-91
14562095
Mol Gen Genet. 1977 Dec 9;157(3):327-32
340929
Nature. 2003 Oct 16;425(6959):737-41
14562106
PLoS One. 2007 Feb 28;2(2):e250
17327914
Nat Genet. 2000 May;25(1):25-9
10802651
Nat Cell Biol. 2007 Apr;9(4):422-7
17310239
Genetics. 1972 May;71(1):157-84
4624779
Genome Biol. 2003;4(4):R28
12702209
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12963-8
12297621
Genome Res. 2007 Sep;17(9):1266-77
17666543
Science. 1999 Aug 6;285(5429):901-6
10436161
Science. 2007 Aug 17;317(5840):916-24
17702937
Nature. 2006 Jun 15;441(7095):840-6
16699522
Genetics. 2008 Mar;178(3):1653-60
18245823
Science. 2008 Apr 18;320(5874):362-5
18420932
Nat Methods. 2008 Aug;5(8):711-8
18622397
Cell. 1981 Aug;25(2):537-46
6116546
RNA. 2002 Aug;8(8):969-80
12212852
Nat Genet. 2000 Jul;25(3):333-7
10888885
Mol Cell. 2006 Feb 3;21(3):319-30
16455487
Nature. 2008 May 1;453(7191):56-64
18451855
J Clin Invest. 2002 Feb;109(4):451-5
11854316
Genetics. 1981 Mar-Apr;97(3-4):639-66
7297851
Genetics. 2005 Apr;169(4):1915-25
15716499
Nat Genet. 1999 Mar;21(3):278-83
10080179
Nature. 2005 Jul 28;436(7050):588-92
16049495
Cell. 2004 Jul 9;118(1):31-44
15242642
Genes Dev. 2005 Dec 1;19(23):2816-26
16322557
Nucleic Acids Res. 2008 Jan;36(Database issue):D637-40
18000002