This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kuepfer, L. Articles by Blank, L. M. Search for Related Content PubMed PubMed Citation Articles by Kuepfer, L. Articles by Blank, L. M. Social Bookmarking                   What's this?

Letter

Metabolic functions of duplicate genes in Saccharomyces cerevisiae

Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland

The roles of duplicate genes and their contribution to the phenomenon of enzyme dispensability are a central issue in molecular and genome evolution. A comprehensive classification of the mechanisms that may have led to their preservation, however, is currently lacking. In a systems biology approach, we classify here back-up, regulatory, and gene dosage functions for the 105 duplicate gene families of Saccharomyces cerevisiae metabolism. The key tool was the reconciled genome-scale metabolic model iLL672, which was based on the older iFF708. Computational predictions of all metabolic gene knockouts were validated with the experimentally determined phenotypes of the entire singleton yeast library of 4658 mutants under five environmental conditions. iLL672 correctly identified 96%-98% and 73%-80% of the viable and lethal singleton phenotypes, respectively. Functional roles for each duplicate family were identified by integrating the iLL672-predicted in silico duplicate knockout phenotypes, genome-scale carbon-flux distributions, singleton mutant phenotypes, and network topology analysis. The results provide no evidence for a particular dominant function that maintains duplicate genes in the genome. In particular, the back-up function is not favored by evolutionary selection because duplicates do not occur more frequently in essential reactions than singleton genes. Instead of a prevailing role, multigene-encoded enzymes cover different functions. Thus, at least for metabolism, persistence of the paralog fraction in the genome can be better explained with an array of different, often overlapping functional roles.

² Corresponding author.
E-mail sauer{at}biotech.biol.ethz.ch; fax 41-1-633 10 51.

¹ Present address: Department of Biochemical and Chemical Engineering, University of Dortmund, 44221 Dortmund, Germany, and the Institute for Analytical Sciences (ISAS), 44139 Dortmund, Germany.

[Supplemental material is available online at www.genome.org.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. Mahadevan and D. R. Lovley The Degree of Redundancy in Metabolic Genes Is Linked to Mode of Metabolism Biophys. J., February 15, 2008; 94(4): 1216 - 1220. [Abstract] [Full Text] [PDF]

				T. Fuhrer, L. Chen, U. Sauer, and D. Vitkup Computational Prediction and Experimental Verification of the Gene Encoding the NAD+/NADP+-Dependent Succinate Semialdehyde Dehydrogenase in Escherichia coli J. Bacteriol., November 15, 2007; 189(22): 8073 - 8078. [Abstract] [Full Text] [PDF]

				T. Shlomi, M. Herrgard, V. Portnoy, E. Naim, B. O. Palsson, R. Sharan, and E. Ruppin Systematic condition-dependent annotation of metabolic genes Genome Res., November 1, 2007; 17(11): 1626 - 1633. [Abstract] [Full Text] [PDF]

				O. Rokhlenko, T. Shlomi, R. Sharan, E. Ruppin, and R. Y. Pinter Constraint-based functional similarity of metabolic genes: going beyond network topology Bioinformatics, August 15, 2007; 23(16): 2139 - 2146. [Abstract] [Full Text] [PDF]

				J. G. Bundy, B. Papp, R. Harmston, R. A. Browne, E. M. Clayson, N. Burton, R. J. Reece, S. G. Oliver, and K. M. Brindle Evaluation of predicted network modules in yeast metabolism using NMR-based metabolite profiling Genome Res., April 1, 2007; 17(4): 510 - 519. [Abstract] [Full Text] [PDF]

				R. Harrison, B. Papp, C. Pal, S. G. Oliver, and D. Delneri Plasticity of genetic interactions in metabolic networks of yeast PNAS, February 13, 2007; 104(7): 2307 - 2312. [Abstract] [Full Text] [PDF]

				B. Teusink, A. Wiersma, D. Molenaar, C. Francke, W. M. de Vos, R. J. Siezen, and E. J. Smid Analysis of Growth of Lactobacillus plantarum WCFS1 on a Complex Medium Using a Genome-scale Metabolic Model J. Biol. Chem., December 29, 2006; 281(52): 40041 - 40048. [Abstract] [Full Text] [PDF]

				R. Khanna, Y. Shen, G. Toledo-Ortiz, E. A. Kikis, H. Johannesson, Y.-S. Hwang, and P. H. Quail Functional Profiling Reveals That Only a Small Number of Phytochrome-Regulated Early-Response Genes in Arabidopsis Are Necessary for Optimal Deetiolation PLANT CELL, September 1, 2006; 18(9): 2157 - 2171. [Abstract] [Full Text] [PDF]