The evolution of modularity in bacterial metabolic networks

Anat Kreimer, Elhanan Borenstein, Uri Gophna, Eytan Ruppin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Deciphering the modular organization of metabolic networks and understanding how modularity evolves have attracted tremendous interest in recent years. Here, we present a comprehensive large scale characterization of modularity across the bacterial tree of life, systematically quantifying the modularity of the metabolic networks of >300 bacterial species. Three main determinants of metabolic network modularity are identified. First, network size is an important topological determinant of network modularity. Second, several environmental factors influence network modularity, with endosymbionts and mammal-specific pathogens having lower modularity scores than bacterial species that occupy a wider range of niches. Moreover, even among the pathogens, those that alternate between two distinct niches, such as insect and mammal, tend to have relatively high metabolic network modularity. Third, horizontal gene transfer is an important force that contributes significantly to metabolic modularity. We additionally reconstruct the metabolic network of ancestral bacterial species and examine the evolution of modularity across the tree of life. This reveals a trend of modularity decrease from ancestors to descendants that is likely the outcome of niche specialization and the incorporation of peripheral metabolic reactions.

Original languageEnglish
Pages (from-to)6976-6981
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
StatePublished - 13 May 2008


  • Bacterial evolution
  • Horizontal gene transfer
  • Lateral gene transfer
  • Network modules
  • Systems biology


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