Use of Genome-Scale Metabolic Models in Evolutionary Systems Biology
One of the major aims of the nascent field of evolutionary systems biology is to test evolutionary hypotheses that are not only realistic from a population genetic point of view but also detailed in terms of molecular biology mechanisms. By providing a mapping between genotype and phenotype for hundreds of genes, genome-scale systems biology models of metabolic networks have already provided valuable insights into the evolution of metabolic gene contents and phenotypes of yeast and other microbial species. Here we review the recent use of these computational models to predict the fitness effect of mutations, genetic interactions, evolutionary outcomes, and to decipher the mechanisms of mutational robustness. While these studies have demonstrated that even simplified models of biochemical reaction networks can be highly informative for evolutionary analyses, they have also revealed the weakness of this modeling framework to quantitatively predict mutational effects, a challenge that needs to be addressed for future progress in evolutionary systems biology.
Key wordsFlux balance analysis (FBA) constraint-based modeling gene essentiality genetic interaction genome evolution fitness landscape metabolic network Saccharomyces cerevisiae
We thank Csaba Pál for suggestions on the manuscript and Kiran Patil and Juan I. Castrillo for comments on the issue of quantitative fitness predictions with FBA. B.P. is supported by The International Human Frontier Science Program Organization, the Hungarian Scientific Research Fund (OTKA), the “Lendület Program,” and the Bolyai Fellowship of the Hungarian Academy of Sciences. R.N. is supported by The Netherlands Genomics Initiative (NGI – Horizon grant) and The Netherlands Organisation for Scientific Research (NWO – VENI Grant).
- 6.Loewe, L., and Hillston, J. (2008) The distribution of mutational effects on fitness in a simple circadian clock. Lect. Notes Bioinf. 5307, 156–175.Google Scholar
- 35.Wolf, J. B., Brodie, E. D., and Wade, M. J. (2000) Epistasis and the Evolutionary Process. New York, NY: Oxford University Press.Google Scholar
- 41.Hurst, L. D., and Pál, C. (2007) Genomic redundancy and dispensability. In: Pagel, M., and Pomiankowski, A. (eds.), Evolutionary Genomics and Proteomics (pp. 141–160). Sunderland, MA: Sinauer Associates Inc.Google Scholar