Genetic variation in Saccharomyces cerevisiae: circuit diversification in a signal transduction network.
The connection between genotype and phenotype was assessed by determining the adhesion phenotype for the same mutation in two closely related yeast strains, S288c and Sigma, using two identical deletion libraries. Previous studies, all in Sigma, had shown that the adhesion phenotype was controlled by the filamentation mitogen-activated kinase (fMAPK) pathway, which activates a set of transcription factors required for the transcription of the structural gene FLO11. Unexpectedly, the fMAPK pathway is not required for FLO11 transcription in S288c despite the fact that the fMAPK genes are present and active in other pathways. Using transformation and a sensitized reporter, it was possible to isolate RPI1, one of the modifiers that permits the bypass of the fMAPK pathway in S288c. RPI1 encodes a transcription factor with allelic differences between the two strains: The RPI1 allele from S288c but not the one from Sigma can confer fMAPK pathway-independent transcription of FLO11. Biochemical analysis reveals differences in phosphorylation between the alleles. At the nucleotide level the two alleles differ in the number of tandem repeats in the ORF. A comparison of genomes between the two strains shows that many genes differ in size due to variation in repeat length.
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Brian L
BL
Chin
Owen
O
Ryan
Fran
F
Lewitter
Charles
C
Boone
Gerald R
GR
Fink
D015966:Gene Expression Regulation, Fungal; D015723:Gene Library; D014644:Genetic Variation; D016681:Genome, Fungal; D020935:MAP Kinase Signaling System / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D020080:Tandem Repeat Sequences; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
C110690:FLO11 protein, S cerevisiae; C100940:FLO8 protein, S cerevisaie; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; C069934:RPI1 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators