- THIS ARTICLE
- Full Text (PDF)
- Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Szathmary, E.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Szathmary, E.
Genetics, Vol 133, 127-132, Copyright © 1993
INVESTIGATIONS |
Do Deleterious Mutations Act Synergistically? Metabolic Control Theory Provides a Partial Answer
E. Szathmary
Laboratory of Mathematical Biology, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, England
Metabolic control theory is used to derive conditions under which two deleterious mutations affecting the dynamics of a metabolic pathway act synergistically. It is found that two mutations tend to act mostly synergistically when they reduce the activity of the same enzyme. If the two mutations affect different enzymes, the conclusion depends on the way that fitness is determined by aspects of the pathway. The cases analyzed are: selection for (1) maximal flux, (2) maximal equilibrium concentration (pool size) of an intermediate, (3) optimal flux, (4) optimal pool size. The respective types of epistasis found are: (1) antagonistic, (2) partly synergistic, (3-4) synergism is likely to predominate over antagonism. This results in somewhat different predictions concerning the effect of metabolic mutations on fitness in prokaryotes and eukaryotes. The fact that bacteria are largely clonal but have often a mosaic gene structure is consistent with expectations from the model.
This article has been cited by other articles:
 |
|
 |
|
  W. J. Dickinson Synergistic Fitness Interactions and a High Frequency of Beneficial Changes Among Mutations Accumulated Under Relaxed Selection in Saccharomyces cerevisiae Genetics, March 1, 2008; 178(3): 1571 - 1578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. H. Barton and S. P. Otto Evolution of Recombination Due to Random Drift Genetics, April 1, 2005; 169(4): 2353 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bonhoeffer, C. Chappey, N. T. Parkin, J. M. Whitcomb, and C. J. Petropoulos Evidence for Positive Epistasis in HIV-1 Science, November 26, 2004; 306(5701): 1547 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. C. Bagheri and G. P. Wagner Evolution of Dominance in Metabolic Pathways Genetics, November 1, 2004; 168(3): 1713 - 1735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Poon and L. Chao Drift Increases the Advantage of Sex in RNA Bacteriophage {Phi}6 Genetics, January 1, 2004; 166(1): 19 - 24. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Agrawal and J. R. Chasnov Recessive Mutations and the Maintenance of Sex in Structured Populations Genetics, June 1, 2001; 158(2): 913 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Peters and P. D. Keightley A Test for Epistasis Among Induced Mutations in Caenorhabditis elegans Genetics, December 1, 2000; 156(4): 1635 - 1647. [Abstract] [Full Text]
|
|
|
|
|
|
T. Lenormand and S. P. Otto The Evolution of Recombination in a Heterogeneous Environment Genetics, September 1, 2000; 156(1): 423 - 438. [Abstract] [Full Text]
|
|
|
|
|
|
B. Bost, C. Dillmann, and D. de Vienne Fluxes and Metabolic Pools as Model Traits for Quantitative Genetics. I. The L-Shaped Distribution of Gene Effects Genetics, December 1, 1999; 153(4): 2001 - 2012. [Abstract] [Full Text]
|
|
|
|
 |
|
 B Oliver, J Singer, V Laget, G Pennetta, and D Pauli Function of Drosophila ovo+ in germ-line sex determination depends on X-chromosome number Development, January 11, 1994; 120(11): 3185 - 3195. [Abstract] [PDF]
|
|