Abstract
BackgroundSelection 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.ResultsGene 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-015-0515-x) contains supplementary material, which is available to authorized users.
Highlights
Selection on proteins is typically measured with the assumption that each protein acts independently
One prediction from coupling between enzymes in a pathway is that when a pathway is under negative selection, that the selective pressure on amino acid change in an individual protein will relate to the sensitivity of pathway function to perturbation of each individual enzyme based upon amino acid changes
Phylogenetic analysis Phylogenetic trees for each of the URA genes involved in the de novo pyrimidine biosynthesis pathway in S. cerevisiae S288c were constructed
Summary
Selection on proteins is typically measured with the assumption that each protein acts independently. A common test for this type of problem is dN/dS, the ratio of nonsynonymous to synonymous nucleotide substitution rates In using this measure (or other measures of selection) to predict functional shifts, one is making the assumption that each protein-coding gene functions independently. One prediction from coupling between enzymes in a pathway is that when a pathway is under negative selection (or other types of selection), that the selective pressure on amino acid change in an individual protein will relate to the sensitivity of pathway function to perturbation of each individual enzyme based upon amino acid changes. Several previous studies have examined the relationship between evolutionary rate and pathway flux, including examination of the effects of network topology [2,3,4,5], a picture linked to underlying evolutionary processes has not yet fully emerged
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