Plasticity of genetic interactions in metabolic networks of yeast
- *Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom; and
- †Department of Zoology, University of Oxford, Oxford OX1 3PS, United Kingdom
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Edited by Charles R. Cantor, Sequenom, Inc., San Diego, CA, and approved December 12, 2006 (received for review August 17, 2006)
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Fig. 1.Model to explain conditional synthetic lethality. A key metabolite (yellow circle) can be synthesized via three independent pathways. Metabolic genes A and B show synthetic lethality in Environment I, where starting nutrients of both pathways are present in the medium. However, B is unable to compensate deletion of A in Environment II, and the double mutant is rescued by the third pathway in Environment III.
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Fig. 2.Distribution of environmental specificity of single-gene deletion phenotypes. Gene deletions showing conditional growth phenotypes were compiled from published large-scale screens (see SI Table 2). Of 4,823 genes not essential for growth on YPD, 963 exhibited lethality or a strong growth defect under at least 1 of the 31 conditions investigated.
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Fig. 3.Distribution of environmental specificity of predicted synthetic lethal interactions. The histogram shows the distribution of the number of simulated environments where each of the 98 gene pairs exhibits synthetic lethality (only gene pairs interacting in at least 1 of the 53 conditions investigated are included).
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Fig. 4.Examples of environment-specific synthetic genetic interactions. (A) Alternative routes to phosphatidylcholine biosynthesis in yeast. Cho2p, phosphatidylethanolamine methyltransferase; Opi3p, phospholipid methyltransferase; Cki1p, choline kinase; Pct1p, cholinephosphate cytidylyltransferase; Cpt1p, sn-1,2-diacylglycerol cholinephosphotransferase; PS, phosphatidylserine; PE, phosphatidylethanolamine; PME, phosphatidyl-N-methylethanolamine; PDME, phosphatidyl-N-dimethylethanolamine; CHO, choline; PCHO, choline phosphate; CDPCHO, CDP-choline; PC, phosphatidylcholine. (B) One member of the SSL pair makes an important individual contribution to growth under a different condition. CHO2 and PCT1 can compensate null mutations in one another under nutrient-rich (YPD) conditions, but the cho2Δ mutant is slow growing on minimal medium. (C) The double deletant becomes viable under a different condition. The SAM1/SAM2 duplicate gene pair, which encodes two distinct forms of S-adenosylmethionine (AdoMet) synthetase, can compensate null mutations in one another, and the double mutants are inviable under nutrient-rich (YPD) conditions. However, addition of AdoMet to the medium yields viable double mutants.
Footnotes
- ‡To whom correspondence may be addressed. E-mail: steve.oliver{at}manchester.ac.uk or d.delneri{at}manchester.ac.uk
- © 2007 by The National Academy of Sciences of the USA
