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Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast

Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast Under laboratory conditions 80% of yeast genes seem not to be essential for viability 1 . This raises the question of what the mechanistic basis for dispensability is, and whether it is the result of selection for buffering or an incidental side product. Here we analyse these issues using an in silico flux model 2,3,4,5 of the yeast metabolic network. The model correctly predicts the knockout fitness effects in 88% of the genes studied 4 and in vivo fluxes. Dispensable genes might be important, but under conditions not yet examined in the laboratory. Our model indicates that this is the dominant explanation for apparent dispensability, accounting for 37–68% of dispensable genes, whereas 15–28% of them are compensated by a duplicate, and only 4–17% are buffered by metabolic network flux reorganization. For over one-half of those not important under nutrient-rich conditions, we can predict conditions when they will be important. As expected, such condition-specific genes have a more restricted phylogenetic distribution. Gene duplicates catalysing the same reaction are not more common for indispensable reactions, suggesting that the reason for their retention is not to provide compensation. Instead their presence is better explained by selection for high enzymatic flux. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast

Papp, Balázs; Pál, Csaba; Hurst, Laurence D.
Nature , Volume 429 (6992) – Jun 10, 2004
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References (50)

Publisher
Springer Journals
Copyright
Copyright © 2004 by Macmillan Magazines Ltd.
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/nature02636
Publisher site
See Article on Publisher Site

Abstract

Under laboratory conditions 80% of yeast genes seem not to be essential for viability 1 . This raises the question of what the mechanistic basis for dispensability is, and whether it is the result of selection for buffering or an incidental side product. Here we analyse these issues using an in silico flux model 2,3,4,5 of the yeast metabolic network. The model correctly predicts the knockout fitness effects in 88% of the genes studied 4 and in vivo fluxes. Dispensable genes might be important, but under conditions not yet examined in the laboratory. Our model indicates that this is the dominant explanation for apparent dispensability, accounting for 37–68% of dispensable genes, whereas 15–28% of them are compensated by a duplicate, and only 4–17% are buffered by metabolic network flux reorganization. For over one-half of those not important under nutrient-rich conditions, we can predict conditions when they will be important. As expected, such condition-specific genes have a more restricted phylogenetic distribution. Gene duplicates catalysing the same reaction are not more common for indispensable reactions, suggesting that the reason for their retention is not to provide compensation. Instead their presence is better explained by selection for high enzymatic flux.

Journal

Nature – Springer Journals

Published: Jun 10, 2004

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