Evolution of a Urea Cycle Enzyme to δ-Crystallin

  • Masataka Mori
  • Tadashi Matsubasa
  • Yoshihiro Amaya
  • Masaki Takiguchi


The urea cycle is closely related to the arginine biosynthetic pathway. It was thus expected that urea cycle enzymes evolved from arginine metabolic enzymes. cDNA clones for the mammalian urea cycle enzymes, ornithine trans- carbamylase, argininosuccinate lyase, and arginase, were isolated and sequenced, and the above view was confirmed. The amino acid sequences of the urea cycle enzymes are around 40% identical to those of the corresponding enzymes of the arginine metabolic pathways in microorganisms.

Sequence comparison revealed an unexpected similarity between argininosuccinate lyase and chicken 5-crystallin, a dominant structural protein in lenses of birds and reptiles. There are two δ-crystallin genes (δ1 and δ2) in the chicken that are tandemly arranged and separated by about 4 kb (kilobase). The δ1 gene encodes the major structural protein in the lens (δ1-crystallin), whereas the nature of the δ2 gene product (δ2-crystallin) is un-known. Rat argininosuccinate lyase is 64% and 69% identical with chicken δ1- and δ2-crystallins respectively. The rat argininosuccinate lyase gene was cloned and its structure was determined. This gene is a single-copy gene about 14 kb long and is split into 16 exons. A comparison with the chicken δ-crystallin genes revealed that all introns interrupt the protein coding regions at homologous positions. This close similarity in structural organization indicates that the chicken δ1- and δ2-crystallin genes evolved by recruitment and duplication of the preexisting argininosuccinate lyase gene and that δ2-crystallin is the direct homologue of argininosuccinate lyase and functions in arginine biosynthesis.


Urea Cycle Lens Protein Ornithine Transcarbamylase Major Structural Protein Carbamyl Phosphate 


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Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  • Masataka Mori
    • 1
  • Tadashi Matsubasa
    • 1
  • Yoshihiro Amaya
    • 1
  • Masaki Takiguchi
    • 1
  1. 1.Institute for Medical GeneticsKumamoto University Medical SchoolKumamotoJapan

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