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1 Biomolecular Sciences, UMIST, Manchester, United Kingdom
2 School of Biological Sciences, University of Manchester, Manchester, United Kingdom
3 Computer science, University of Manchester, Manchester, United Kingdom
4 Dipartimento di Scienze Biomoleculari e Biotechnologie, Universita degli Studi di Milano, Milano, Italy
* To whom correspondence should be addressed. E-mail: lubomira.stateva{at}umist.ac.uk.
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
mutant, constructed in the Saccharomyces cerevisiae reference strain FY23, revealed altered expression of approximately 11% of protein encoding genes. The mutant, characterised by constitutive activation of the Ras/cAMP pathway, has increased sensitivity to stress, reduced ability to assimilate non-fermentable carbon sources and some cell wall integrity defects. Applying the MIPS functional categories revealed increased expression of genes related to ribosome biogenesis and down-regulation of genes in the cell rescue, defence, cell death and ageing category, suggesting a decreased response to stress conditions. A reduced level of gene expression in the Unfolded Protein Response pathway 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.
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