Abstract

BackgroundComparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. By selecting taxa representative of different lineages or lifestyles and using a comprehensive set of descriptors of the structure and complexity of their metabolic networks, one can highlight both qualitative and quantitative differences in the metabolic organization of species subject to distinct evolutionary paths or environmental constraints.ResultsWe used a novel representation of metabolic networks, termed network of interacting pathways or NIP, to focus on the modular, high-level organization of the metabolic capabilities of the cell. Using machine learning techniques we identified the most relevant aspects of cellular organization that change under evolutionary pressures. We considered the transitions from prokarya to eukarya (with a focus on the transitions among the archaea, bacteria and eukarya), from unicellular to multicellular eukarya, from free living to host-associated bacteria, from anaerobic to aerobic, as well as the acquisition of cell motility or growth in an environment of various levels of salinity or temperature. Intuitively, we expect organisms with more complex lifestyles to have more complex and robust metabolic networks. Here we demonstrate for the first time that such organisms are not only characterized by larger, denser networks of metabolic pathways but also have more efficiently organized cross communications, as revealed by subtle changes in network topology. These changes are unevenly distributed among metabolic pathways, with specific categories of pathways being promoted to more central locations as an answer to environmental constraints.ConclusionsCombining methods from graph theory and machine learning, we have shown here that evolutionary pressures not only affects gene and protein sequences, but also specific details of the complex wiring of functional modules in the cell. This approach allows the identification and quantification of those changes, and provides an overview of the evolution of intracellular systems.

Highlights

  • Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks

  • Unicellular eukarya were opposed to multicellular eukarya to reveal how the more stable environment and cellular differentiation that a multicellular body implies impacted the organization of metabolism

  • Aerobic bacteria were compared to anaerobes and to facultative aerobic bacteria as a potential negative control; in Raymond et al [22], the authors demonstrated that aerobic metabolism had little impact on the rewiring of metabolic network structure during evolution, network size was affected

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Summary

Introduction

Comparison of metabolic networks across species is a key to understanding how evolutionary pressures shape these networks. Network representations are increasingly used to Networks are used in comparative studies to highlight the differences and similarities existing in the organization of the intracellular mechanisms of multiple species. Studies have been published that compare the topological features of metabolic networks for taxa sampled from all three kingdoms of life [14,15,16,17]. These investigations shed light on how these metabolic networks differ among the archaea, bacteria and eukarya, as a result of natural selection processes [18]. The results show that while some properties are shared by all taxa (e.g., their metabolic networks are all scale-free), bacteria species distinguish themselves over archaea and eukarya by having a shorter network average path length [15,16]

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