Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast.
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.
Department of Molecular Biology, University of Wyoming, Laramie, WY, 82071, USA. rhermans@uwyo.edu.|Department of Biology and Center for Computational Genetics and Genomics, Temple University, Philadelphia, PA, 19122, USA. rhermans@uwyo.edu.
Russell A
RA
Hermansen
Division of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ, 85721, USA. mannakee@email.arizona.edu.
Brian K
BK
Mannakee
Department of Biology and Lund Protein Production Platform, Lund University, 22362, Lund, Sweden. wolfgang.knecht@biol.lu.se.
Wolfgang
W
Knecht
Department of Molecular Biology, University of Wyoming, Laramie, WY, 82071, USA. daliberles@temple.edu.|Department of Biology and Center for Computational Genetics and Genomics, Temple University, Philadelphia, PA, 19122, USA. daliberles@temple.edu.
David A
DA
Liberles
Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, 85721, USA. rgutenk@email.arizona.edu.
Ryan N
RN
Gutenkunst
D053898:Biosynthetic Pathways; D019143:Evolution, Molecular; D009154:Mutation; D010802:Phylogeny; D011743:Pyrimidines / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*
D011743:Pyrimidines; D029701:Saccharomyces cerevisiae Proteins