Comparison of the evolution rates of cytosolic and mitochondrial aspartate aminotransferase.

Abstract

TWO isoenzymes of aspartate aminotransf erase (AAT) occur in animal and possibly in all eukaryotic cells, one in the cytosol (cAAT) and the other in the mitochondria (mAAT)1. Both isoenzymes are composed of two identical polypeptide chains of about 400 amino acid residues and their reaction mechanisms and kinetic features are essentially the same1,2. They are homologous proteins, as evidenced by 48% sequence identity of the two isoenzymes from pig3,4, and are both coded for by nuclear DNA and synthesised by cytosolic ribosomes5–7. Comparison of the isoenzymes from pig with those from chicken by quantitative microcomplement fixation has shown that the interspecies similarity of the mitochondrial isoenzymes markedly exceeds that of the cytosolic isoenzymes8. The same conclusion has been reached by comparison of the known amino acid sequences of the pig isoenzymes3,4 with the chicken isoenzymes, for which more than half of their sequences have already been determined. The sequence identity of the two cytosolic isoenzymes seems to be approximately 50% (Y. M. Torchinsky, personal communication), whereas that of the two mitochondrial isoenzymes is about 85% (ref. 9 and U. Hausner, P. C., K. J. Wilson, unpublished). In the present study, the immunological interspecies comparison of the two isoenzymes was extended to species of all vertebrate classes. The evolution of the two compartmented isoenzymes was found to have proceeded at identical and constant rates throughout the development of the nonmammalian vertebrates. After the emergence of mammals, however, the rate of evolution of the cytosolic isoenzyme more than doubled while its mitochondrial counterpart retained the slower rate of the nonmammalian vertebrates.