BACKGROUND: Selection on proteins is typically measured with the assumption that each protein acts independently. However, selection more likely acts at higher levels of biological organization, requiring an integrative view of protein function. Here, we built a kinetic model for de novo pyrimidine biosynthesis in the yeast Saccharomyces cerevisiae to relate pathway function to selective pressures on individual protein-encoding genes. RESULTS: Gene families across yeast were constructed for each member of the pathway and the ratio of nonsynonymous to synonymous nucleotide substitution rates (dN/dS) was estimated for each enzyme from S. cerevisiae and closely related species. We found a positive relationship between the influence that each enzyme has on pathway function and its selective constraint. CONCLUSIONS: We expect this trend to be locally present for enzymes that have pathway control, but over longer evolutionary timescales we expect that mutation-selection balance may change the enzymes that have pathway control.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/610280 |
| Date | January 2015 |
| Creators | Hermansen, Russell A., Mannakee, Brian K., Knecht, Wolfgang, Liberles, David A., Gutenkunst, Ryan N. |
| Contributors | Department of Molecular Biology, University of Wyoming, Department of Biology and Center for Computational Genetics and Genomics, Temple University, Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Department of Biology and Lund Protein Production Platform, Lund University, Department of Molecular and Cellular Biology, University of Arizona |
| Publisher | BioMed Central Ltd |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | Article |
| Rights | © 2015 Hermansen et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) |
| Relation | http://www.biomedcentral.com/1471-2148/15/232 |
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