Evolutionary Relationship of a Fish C Type Lactate Dehydrogenase to Other Vertebrate Lactate Dehydrogenase Isozymes

Abstract

It is assumed that the genes for the three types of vertebrate lactate dehydrogenase isozymes (A, B, and C) arose from an ancestral lactate dehydrogenase gene by a mechanism involving gene duplications. The currently accepted model was originally proposed by Holmes in 1972 (FEBS Lett. 28: 51–55). The main points in this proposal are as follows: (1) the ancestral lactate dehydrogenase was an A type; (2) the gene for this A type lactate dehydrogenase duplicated to produce the A and B forms; and (3) the C isozymes of fish and warm-blooded vertebrates are derived from B types by successive, independent gene duplication events. More structural data have become available since this model was first put forward, and Li et al. (1983. J. Biol. Chem. 258: 7029–7032) have shown that rodent C type lactate dehydrogenases appear to be ancestral to the A and B forms. We have extended Li's reevaluation of the evolutionary relationships among vertebrate lactate dehydrogenase isozymes. Our analysis indicates that there is no significant difference in the rates of evolution along the A, B, or C lineages. This confirms that a C type rather than an A type lactate dehydrogenase was the ancestral form. A duplication of the gene for this C type gave rise to the gene which, by a further gene duplication, yielded the A and B type lactate dehydrogenase genes. In addition, amino acid compositional data reveal that the C type lactate dehydrogenase from Atlantic cod (Gadus morhua) and the C type lactate dehydrogenase isozymes of rodents are homologous proteins that are the result of divergent evolution via speciation events rather than by independent gene duplications. This novel interpretation of lactate dehydrogenase isozyme evolution is discussed with respect to the tissue specificities of C type lactate dehydrogenases in vertebrates.