Phenotypic impact of regulatory noise in cellular stress-response pathways.
Recent studies indicate that intrinsic promoter-mediated gene expression noise can confer a selective advantage under acute environmental stress by providing beneficial phenotypic diversity within cell populations. To investigate how extrinsic gene expression noise impacts the fitness of cell populations under stress, we engineered two nearly isogenic budding yeast strains; one carrying a two-step regulatory cascade that allows for precise control of the noise transmitted from a transcriptional regulator to a downstream stress-inducing gene, and one carrying a network with low constant upstream noise. The fitness and gene expression of these strains were compared under acute and prolonged stress exposure. Using a phenomenological modeling approach, we predicted that increased noise should confer a fitness advantage under high stress conditions, but reciprocally reduce the resistance of the population to low stress. The model also predicted that extrinsic noise might serve as a basis for phenotypic plasticity whereby gene expression distributions are modulated in response to prolonged stress. Experimentally, we confirmed the predicted differential fitness advantage of extrinsic noise under acute stress, as well as the predicted modulation of gene expression under prolonged stress. However, contrary to model predictions, strains with low and high extrinsic noise showed very similar adaptive responses to prolonged stress. This suggests that while phenotypic heterogeneity generated by noise in regulatory signals can confer increased robustness to acute stress, it is not a requirement for the observed long-term phenotypic plasticity.
Zhuravel
Daniil
D
Fraser
Dawn
D
St-Pierre
Simon
S
Tepliakova
Lioudmila
L
Pang
Wyming L
WL
Hasty
Jeff
J
Kærn
Mads
M
Yeast. 1997 Jul;13(9):837-48
9234672
Mol Microbiol. 2009 Mar;71(6):1333-40
19220745
Nat Rev Genet. 2005 Jun;6(6):451-64
15883588
Nat Genet. 2002 May;31(1):69-73
11967532
Nat Rev Microbiol. 2006 Aug;4(8):577-87
16845428
Yeast. 1993 Jun;9(6):575-82
8346673
Science. 2008 Apr 4;320(5872):65-8
18388284
Mol Syst Biol. 2008;4:170
18319722
Science. 2004 Jun 18;304(5678):1811-4
15166317
Science. 2005 Mar 25;307(5717):1965-9
15790857
Nature. 2000 Jun 1;405(6786):590-3
10850721
Nat Genet. 2007 Aug;39(8):945-9
17660811
Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7963-8
10859354
Nature. 2006 Jun 15;441(7095):840-6
16699522
PLoS Comput Biol. 2008 Aug 15;4(8):e1000125
18716677
Nat Rev Genet. 2009 May;10(5):336-42
19337290
Sci STKE. 2002 Jul 30;2002(143):pe33
12149512
PLoS Biol. 2004 Jun;2(6):e137
15124029
Int J Food Microbiol. 2002 Sep 15;78(1-2):19-30
12222634
Nat Genet. 2005 Sep;37(9):937-44
16086016
Nat Genet. 2006 Jun;38(6):636-43
16715097
Nature. 2003 Apr 10;422(6932):633-7
12687005
Mol Syst Biol. 2009;5:299
19690568
Mol Cell. 2006 Dec 28;24(6):853-65
17189188
Science. 2007 Jul 27;317(5837):526-9
17569828
Cell. 2008 Oct 17;135(2):216-26
18957198
Science. 2005 Mar 25;307(5717):1962-5
15790856
Mol Cell. 2007 Dec 14;28(5):755-60
18082601
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3581-6
15738412
Nat Rev Genet. 2008 Aug;9(8):583-93
18591982
Mol Syst Biol. 2006;2:41
16883354
Nat Rev Microbiol. 2006 Apr;4(4):259-71
16541134
Biophys J. 2007 Dec 1;93(11):L55-7
17890398