Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast. (December 2015)

• Record Type: Journal Article
• Authors: Hermansen, Russell; Mannakee, Brian; Knecht, Wolfgang; Liberles, David; Gutenkunst, Ryan
• Is Part Of: BMC evolutionary biology. Volume 15(2015)Supplement 1
• Page Start: 1
• Page End: 13
• Publication Date: 2015-12
• Subjects: Evolutionary systems biology -- Metabolic pathway evolution -- Phylogenetics -- Kinetic model -- Enzyme evolution -- Substitution rate; Evolution (Biology) -- Periodicals; 576.805
• DOI: 10.1186/s12862-015-0515-x
• Languages: English
• ISSNs: 1471-2148

Abstract

Abstract 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 forde novo pyrimidine biosynthesis in the yeastSaccharomyces 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 fromS. 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.