Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast

Russell A. Hermansen, Brian K. Mannakee, Wolfgang Knecht, David A. Liberles, Ryan N. Gutenkunst

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


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.

Original languageEnglish (US)
Article number232
JournalBMC Evolutionary Biology
Issue number1
StatePublished - Oct 28 2015


  • Enzyme evolution
  • Evolutionary systems biology
  • Kinetic model
  • Metabolic pathway evolution
  • Phylogenetics
  • Substitution rate

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics


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