Environmental and genetic perturbations reveal different networks of metabolic regulation

Anthony J. Greenberg, Sean R. Hackett, Lawrence G. Harshman, Andrew G. Clark

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Progress in systems biology depends on accurate descriptions of biological networks. Connections in a regulatory network are identified as correlations of gene expression across a set of environmental or genetic perturbations. To use this information to predict system behavior, we must test how the nature of perturbations affects topologies of networks they reveal. To probe this question, we focused on metabolism of Drosophila melanogaster. Our source of perturbations is a set of crosses among 92 wild-derived lines from five populations, replicated in a manner permitting separate assessment of the effects of genetic variation and environmental fluctuation. We directly assayed activities of enzymes and levels of metabolites. Using a multivariate Bayesian model, we estimated covariance among metabolic parameters and built fine-grained probabilistic models of network topology. The environmental and genetic co-regulation networks are substantially the same among five populations. However, genetic and environmental perturbations reveal qualitative differences in metabolic regulation, suggesting that environmental shifts, such as diet modifications, produce different systemic effects than genetic changes, even if the primary targets are the same.

Original languageEnglish (US)
Article number563
JournalMolecular Systems Biology
Issue number1
StatePublished - 2011
Externally publishedYes


  • Bayesian model
  • G matrix
  • hierarchical model
  • metabolic network

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Agricultural and Biological Sciences
  • Applied Mathematics


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