Phylogenetic analysis and molecular evolution of guanine deaminases: from guanine to dendrites

J Mol Evol. 2009 Mar;68(3):227-35. doi: 10.1007/s00239-009-9205-x. Epub 2009 Feb 17.


Guanine deaminase (GDA; guanase) is a ubiquitous enzyme that catalyzes the first step of purine metabolism by hydrolytic deamination of guanine, resulting in the production of xanthine. This hydrolase subfamily member plays an essential role in maintaining homeostasis of cellular triphosphate nucleotides for energy, signal transduction pathways, and nitrogen sources. In mammals, GDA protein levels can play a role in neuronal development by regulating dendritic arborization. We previously demonstrated that the most abundant alternative splice form of GDA in mammals, termed cypin (cytosolic PSD-95 interactor), interacts with postsynaptic density proteins, regulates microtubule polymerization, and increases dendrite number. Since purine metabolism and dendrite development were previously thought to be independent cellular processes, this multifunctional protein serves as a new target for the treatment of cognitive disorders characterized by aberrant neuronal morphology and purine metabolism. Although the enzymatic activity of GDA has been conserved during evolution from prokaryotes to higher eukaryotes, a detailed evolutionary assessment of the principal domains in GDA proteins has not yet been put forward. In this study, we perform a complete evolutionary analysis of the full-length sequences and the principal domains in guanine deaminases. Furthermore, we reconstruct the molecular phylogeny of guanine deaminases with neighbor-joining, maximum-likelihood, and UPGMA methods of phylogenetic inference. This study can act as a model whereby a universal housekeeping enzyme may be adapted to act also as a key regulator of a developmental process.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Conserved Sequence
  • Dendrites
  • Eukaryotic Cells
  • Evolution, Molecular*
  • Guanine / metabolism
  • Guanine Deaminase / genetics*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Phylogeny*
  • Prokaryotic Cells
  • Protein Interaction Domains and Motifs / genetics
  • Rats
  • Zinc / metabolism


  • Carrier Proteins
  • Nerve Tissue Proteins
  • Guanine
  • Gda protein, rat
  • Guanine Deaminase
  • Zinc