Zoological Studies

Vol. 37 No. 1, 1998

Structure, Regulation and Evolution of Vertebrate Lactate Dehydrogenase Genes

Steven Shoei-Lung Li

Institute of Life Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan 804

Steven Shoei-Lung Li (1998) In vertebrates, L-lactate dehydrogenase (LDH) isozymes A (muscle) and B (heart) are best suited for pyruvate reduction and lactate oxidation, respectively. In mammals and columbid birds, a 3rd LDH-C isozyme is expressed in testis. In advanced teleost fish a 3rd LDH isozyme is found only in the eye, but in more primitive teleosts, if it is present, it has a generalized distribution. The evolutionary relationships among these 3rd forms of LDH isozymes have not been completely resolved.
We have cloned the cDNAs encoding LDH-A, LDH-B, and/or LDH-C isozymes from the human, mouse, rat, porcine, pigeon, alligator, lizard, turtle, Xenopus, and a nematode. We have determined the exon-intron organization of human LDH-A, LDH-B, and LDH-C genes, and the complete sequence of 12 851 nucleotides of the mouse LDH-A gene. The protein-coding sequences of the mammalian LDH-A, LDH-B, and LDH-C genes, as well as duck LDH-B gene, are interrupted by 6 introns at homologous positions. The expression of vertebrate LDH-A, LDH-B, and LDH-C genes is tissue specific and developmentally regulated. Expression of the mammalian LDH-A gene was also shown to be induced by cAMP and estrogen.
In collaboration with Dr. Wen-Hsiung Li, we analyzed the evolutionary relationships among vertebrate LDH isoyzmes. Contrary to the common opinion that the turtle lineage branched off before the divergence between the lizard/alligator and bird lineages, the turtle lineage was found clustered with either the alligator lineage or the alligator-bird clade, while the lizard lineage was found to have branched off before the divergence between the alligator/turtle and bird lineages. The pigeon testicular LDH-C gene was evidently duplicated from the LDH-B (heart) gene, so it is not orthologous to the mammalian testicular LDH-C genes, which appear to be derived from the LDH-A (muscle) gene.

Key words: Genes, Isozymes, Protein sequences, Phylogenetic tree.

*Correspondence: Tel: 886-7-5252379. Fax: 886-7-5252360. E-mail: lissl@mail.nsysu.edu.tw