The evolutionary history of the first three enzymes in pyrimidine biosynthesis

Bioessays. 1993 Mar;15(3):157-64. doi: 10.1002/bies.950150303.


Some metabolic pathways are nearly ubiquitous among organisms: the genes encoding the enzymes for such pathways must therefore be ancient and essential. De novo pyrimidine biosynthesis is an example of one such metabolic pathway. In animals a single protein called CAD carries the first three steps of this pathway. The same three enzymes in prokaryotes are associated with separate proteins. The CAD gene appears to have evolved through a process of gene duplication and DNA rearrangement, leading to an in-frame gene fusion encoding a chimeric protein. A driving force for the creation of eukaryotic genes encoding multienzymatic proteins such as CAD may be the advantage of coordinate expression of enzymes catalyzing steps in a biosynthetic pathway. The analogous structure in bacteria is the operon. Differences in the translational mechanisms of eukaryotes and prokaryotes may have dictated the different strategies used by organisms to evolve coordinately regulated genes.

Publication types

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

MeSH terms

  • Animals
  • Aspartate Carbamoyltransferase / genetics*
  • Bacteria / metabolism
  • Biological Evolution
  • Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / genetics*
  • Dihydroorotase / genetics*
  • Mammals / metabolism
  • Multienzyme Complexes / genetics*
  • Pyrimidines / biosynthesis*


  • CAD trifunctional enzyme
  • Multienzyme Complexes
  • Pyrimidines
  • Aspartate Carbamoyltransferase
  • Dihydroorotase
  • Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)