Copy number alterations among mammalian enzymes cluster in the metabolic network

Mol Biol Evol. 2011 Feb;28(2):1111-21. doi: 10.1093/molbev/msq296. Epub 2010 Nov 3.


Using two high-quality human metabolic networks, we employed comparative genomics techniques to infer metabolic network structures for seven other mammals. We then studied copy number alterations (CNAs) in these networks. Using a graph-theoretic approach, we show that the pattern of CNAs is distinctly different from the random distributions expected under genetic drift. Instead, we find that changes in copy number are most common among transporter genes and that the CNAs differ depending on the mammalian lineage in question. Thus, we find an excess of transporter genes in cattle involved in the milk production, secretion, and regulation. These results suggest a potential role for dosage selection in the evolution of mammalian metabolic networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Gene Dosage
  • Humans
  • Mammals / metabolism*
  • Membrane Transport Proteins / genetics
  • Metabolic Networks and Pathways*
  • Milk / metabolism


  • Membrane Transport Proteins