Environmental and genetic perturbations reveal different networks of metabolic regulation

Authors

  • Anthony J Greenberg,

    Corresponding author
    1. Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA
    • Corresponding author. Department of Molecular Biology and Genetics, Cornell University, 101 Biotechnology Building, Ithaca, NY 14853, USA. Tel.: +1 607 255 1707; Fax: +1 607 255 4698; E-mail: ajg67@cornell.edu

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  • Sean R Hackett,

    1. Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA
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    • Present address: Graduate Program in Quantitative and Computational Biology, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA

  • Lawrence G Harshman,

    1. School of Biological Sciences, University of Nebraska-Lincoln, Lincoln, NE, USA
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  • Andrew G Clark

    1. Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA
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Abstract

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.

Synopsis

Measurement of metabolic and physiological parameters in replicated crosses of Drosophila melanogaster inbred lines reveals that environmental and genetic perturbations uncover substantially different networks of metabolic regulation.

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  • We collected extensive data on enzyme activities and physiological parameters from replicated crosses of D. melanogaster inbred lines.
  • We implemented a multivariate hierarchical Bayesian model to separately assess genetic and environmental covariation among system components and infer metabolic regulatory networks.
  • Networks revealed by both environmental and genetic perturbations are similar among populations and between sexes.
  • Environmental and genetic networks differ substantially, suggesting that environmental changes and mutations would have different systemic effects even when their primary targets are the same.

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