Metabolic Flux and Sequence Conservation

Source: Bilu, Y., Shlomi, T., Barkai, N., and Ruppin, E. Conservation of expression and sequence of metabolic genes is reflected by activity across metabolic states. 2006. PLoS Computational Biology, 2(8):e106

The authors use flux balance analysis (FBA) to create an optimal solution set for metabolic genes in various media conditions. They then compare the flux in this set for individual reactions to evolution rate of the protein-coding region, promoter, and expression levels. The authors found rough correlation in the expected manner: lower flux variability genes show higher conservation across species. Additionally, genes found to be active throughout different media conditions were found to be well conserved.

Other notes
-in FBA’s optimal solution space there are missing constraints to the model, though it has been shown that models still carry meaningful biological info
-flux values show moderate, statistically significant correlation with corresponding gene expression levels and protein abundance
-flux variability analysis: difference between max and min flux values in the space of optimal flux distributions for each reaction
-expression divergence score: expression patterns among four yeast strains
-promoter conservation score: based on three yeast species’ conservation of S. cerevisiae transcription factor binding sites
-moderate, statistically significant correlation between flexibility scores and expression divergence score, promoter conservation score
-possible that high flexibility score means the genes are in pathways that have alternatives
-of the 50 genes with highest flex score, 6% are essential, whereas 17% of the 89 zero-flex genes are essential
-statistically significant correlation between knockout growth rate (For metabolic genes) and evolutionary rate
-best predictor for evolutionary rate is the expression level of the encoded gene
-“Previous studies suggest that the predicted variability in metabolic states may represent heterogeneous metabolic behaviors of individuals within a cell population”


I found this study short and sweet. A simple question: Do highly conserved genes have more rigid optimum activities? So for enzymes that are not metabolically constrained we see a greater diversity in sequence. This makes senses, mess with the choke-points and you screw up a pathway, tinker with some of the non rate-limiting genes and there isn't as much a problem.