Physiol. Genomics AJP: Regulatory, Integrative and Comparative Physiology
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Physiol. Genomics 16: 107-118, 2003. First published October 21, 2003; doi:10.1152/physiolgenomics.00139.2003
1094-8341/03 $5.00
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Received 22 August 2002; accepted in final form 14 October 2003.
Physiological Genomics 16:107-118 (2003)
1094-8341/03 $5.00 © 2003 American Physiological Society

Transcriptome profiling of a Saccharomyces cerevisiae mutant with a constitutively activated Ras/cAMP pathway

D. L. Jones 1, J. Petty 2, D. C. Hoyle 3, A. Hayes 2, E. Ragni 4, L. Popolo 4, S. G. Oliver 2 and L. I. Stateva 1

1 Department of Biomolecular Sciences, University of Manchester Institute of Science and Technology (UMIST), Manchester M60 1QD
2 School of Biological Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom
3 Department of Computer Science, University of Manchester, Manchester, M13 9PT, United Kingdom
4 Dipartimento di Scienze Biomolecolari e Biotecnologie, Università degli Studi di Milano, Milan 20133, Italy

Often changes in gene expression levels have been considered significant only when above/below some arbitrarily chosen threshold. We investigated the effect of applying a purely statistical approach to microarray analysis and demonstrated that small changes in gene expression have biological significance. Whole genome microarray analysis of a pde2{Delta} mutant, constructed in the Saccharomyces cerevisiae reference strain FY23, revealed altered expression of ~11% of protein encoding genes. The mutant, characterized by constitutive activation of the Ras/cAMP pathway, has increased sensitivity to stress, reduced ability to assimilate nonfermentable carbon sources, and some cell wall integrity defects. Applying the Munich Information Centre for Protein Sequences (MIPS) functional categories revealed increased expression of genes related to ribosome biogenesis and downregulation of genes in the cell rescue, defense, cell death and aging category, suggesting a decreased response to stress conditions. A reduced level of gene expression in the unfolded protein response pathway (UPR) was observed. Cell wall genes whose expression was affected by this mutation were also identified. Several of the cAMP-responsive orphan genes, upon further investigation, revealed cell wall functions; others had previously unidentified phenotypes assigned to them. This investigation provides a statistical global transcriptome analysis of the cellular response to constitutive activation of the Ras/cAMP pathway.

constitutive activation of PKA by PDE2 deletion; Ras/cAMP pathway; cell wall integrity




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