Evolutionary recruitment of biochemically specialized subdivisions of Family I within the protein superfamily of aminotransferases.

It is generally accepted that ancient organisms must have possessed small genomes producing fewer gene products than contemporary organisms. Since the evolution of high specificity is surely a demanding process, primitive enzymes are likely to have been broad-specificity catalysts, utilizing a family of related substrates and producing a family of related products (67). Events of gene duplication could then have facilitated the differential narrowing of substrate specificities to produce the expanded repertoire of specialized enzymes seen in contemporary organisms. The gene recruitment hypothesis (27) states that the latter scenario is the basis for the emergence of gene families whose members catalyze a variety of related enzymatic reactions. The ever-enlarging database of deduced amino acid sequences is revealing the outlines of many large and stillgrowing gene families whose common ancestor may often have been a fundamental multipurpose unit in the primitive systems referred to above. Although numerous expected homology relationships have been confirmed, sometimes reasonable predictions of homology relationships have not been correct. For example, since the beta subunit of tryptophan synthase (TrpB) in Escherichia coli is a pyridoxal 59-phosphate (PLP)-dependent enzyme that can be replaced functionally by a constitutively expressed tryptophanase (also PLP dependent) and because both catalyze b-elimination reactions, homology was predicted (27). However, TrpB and tryptophanase appear to be analogous rather than homologous (1, 47). It is additionally striking that wholly unanticipated homologs of TrpB have surfaced (47), namely, threonine synthase, threonine dehydratase, and D-serine dehydratase (all PLP-dependent enzymes). Homolog relationships that are perhaps even more surprising have also emerged. For example, pyruvate oxidase (a peripheral-membrane redox flavoprotein) and the large catalytic subunit of acetohydroxyacid synthase isoenzymes (cytoplasmic proteins in the common pathway of isoleucine-valine biosynthesis) are homologs (4). In such instances of unforeseen homology, it has inevitably been possible to rationalize a common ancestor in terms of related mechanistic features of catalysis. Indeed, the elucidation of such relationships has been quite illuminating at both the biochemical and evolutionary levels. In this minireview the model of gene recruitment is used to analyze one section of aminotransferase homologs whose membership includes a large gene family of orthologous and paralogous proteins.