• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of pnasPNASInfo for AuthorsSubscriptionsAboutThis Article
Proc Natl Acad Sci U S A. Jan 1, 1993; 90(1): 242–246.

Sequence analysis of teleost retina-specific lactate dehydrogenase C: evolutionary implications for the vertebrate lactate dehydrogenase gene family.


At least two gene duplication events have led to the three lactate dehydrogenase (LDH; EC isozymes (LDH-A, LDH-B, and LDH-C) of chordates. The prevailing model for the evolution of the LDH loci involves duplication of a primordial LDH locus near the origin of vertebrates, giving rise to Ldh-A and Ldh-B. A third locus, designated Ldh-C, is expressed in the spermatocytes of mammals and a single family of birds and in the eye or liver tissues of teleost fishes. Ldh-C might have arisen independently in these taxa as duplications of either Ldh-A or Ldh-B. Several authors have challenged this traditional hypothesis on the basis of amino acid sequence and immunological similarity of the three LDH isozymes. They suggest that the primordial LDH gene was duplicated to form Ldh-C and a locus that later gave rise to Ldh-A and Ldh-B. We have differentiated between these hypotheses by determining the cDNA sequence of the retina-specific LDH-C from a teleost, Fundulus heteroclitus. On the basis of amino acid sequence similarity, we conclude that the LDH-C isozymes in fish and mammals are not orthologous but derive from independent gene duplications. Furthermore, our phylogenetic analyses support previous hypotheses that teleost Ldh-C is derived from a duplication of the Ldh-B locus.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Britten RJ, Davidson EH. Repetitive and non-repetitive DNA sequences and a speculation on the origins of evolutionary novelty. Q Rev Biol. 1971 Jun;46(2):111–138. [PubMed]
  • Kimura M, Ohta T. On some principles governing molecular evolution. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2848–2852. [PMC free article] [PubMed]
  • Needleman SB, Wunsch CD. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970 Mar;48(3):443–453. [PubMed]
  • Whitt GS. Genetic, developmental and evolutionary aspects of the lactate dehydrogenase isozyme system. Cell Biochem Funct. 1984 Jul;2(3):134–139. [PubMed]
  • Markert CL, Shaklee JB, Whitt GS. Evolution of a gene. Multiple genes for LDH isozymes provide a model of the evolution of gene structure, function and regulation. Science. 1975 Jul 11;189(4197):102–114. [PubMed]
  • Holmes RS. Evolution of lactate dehydrogenase genes. FEBS Lett. 1972 Nov 15;28(1):51–55. [PubMed]
  • Li SS, Fitch WM, Pan YC, Sharief FS. Evolutionary relationships of vertebrate lactate dehydrogenase isozymes A4 (muscle), B4 (heart), and C4 (testis). J Biol Chem. 1983 Jun 10;258(11):7029–7032. [PubMed]
  • Baldwin J, Lake PS, Moon TW. Immunochemical evidence that the single lactate dehydrogenase of lampreys is more similar to LDHB4 than to LDHA4 of hagfish. J Exp Zool. 1987 Jan;241(1):1–8. [PubMed]
  • Crawford DL, Constantino HR, Powers DA. Lactate dehydrogenase-B cDNA from the teleost Fundulus heteroclitus: evolutionary implications. Mol Biol Evol. 1989 Jul;6(4):369–383. [PubMed]
  • Whitt GS. Homology of lactate dehydrogenase genes: E gene function in the teleost nervous system. Science. 1969 Nov 28;166(3909):1156–1158. [PubMed]
  • Sensabaugh GF, Jr, Kaplan NO. A lactate dehydeogenase specific to the liver of gadoid fish. J Biol Chem. 1972 Jan 25;247(2):585–593. [PubMed]
  • Shaklee JB, Kepes KL, Whitt GS. Specialized lactate dehydrogenase isozymes: the molecular and genetic basis for the unique eye and liver LDHs of teleost fishes. J Exp Zool. 1973 Aug;185(2):217–240. [PubMed]
  • Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. [PubMed]
  • Marchuk D, Drumm M, Saulino A, Collins FS. Construction of T-vectors, a rapid and general system for direct cloning of unmodified PCR products. Nucleic Acids Res. 1991 Mar 11;19(5):1154–1154. [PMC free article] [PubMed]
  • Hediger MA, Frank G, Zuber H. Structure and function of L-lactate dehydrogenases from thermophilic and mesophilic bacteria, IV. The primary structure of the mesophilic lactate dehydrogenase from Bacillus subtilis. Biol Chem Hoppe Seyler. 1986 Sep;367(9):891–903. [PubMed]
  • Minowa T, Iwata S, Sakai H, Masaki H, Ohta T. Sequence and characteristics of the Bifidobacterium longum gene encoding L-lactate dehydrogenase and the primary structure of the enzyme: a new feature of the allosteric site. Gene. 1989 Dec 21;85(1):161–168. [PubMed]
  • Ono M, Matsuzawa H, Ohta T. Nucleotide sequence and characteristics of the gene for L-lactate dehydrogenase of Thermus aquaticus YT-1 and the deduced amino acid sequence of the enzyme. J Biochem. 1990 Jan;107(1):21–26. [PubMed]
  • Hondred D, Hanson AD. Hypoxically inducible barley lactate dehydrogenase: cDNA cloning and molecular analysis. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7300–7304. [PMC free article] [PubMed]
  • Taylor SS. Amino acid sequence of dogfish muscle lactate dehydrogenase. J Biol Chem. 1977 Mar 10;252(5):1799–1806. [PubMed]
  • Hirota Y, Katsumata A, Takeya T. Nucleotide and deduced amino acid sequences of chicken lactate dehydrogenase-A. Nucleic Acids Res. 1990 Nov 11;18(21):6432–6432. [PMC free article] [PubMed]
  • Ishiguro N, Osame S, Kagiya R, Ichijo S, Shinagawa M. Primary structure of bovine lactate dehydrogenase-A isozyme and its synthesis in Escherichia coli. Gene. 1990 Jul 16;91(2):281–285. [PubMed]
  • Kiltz HH, Keil W, Griesbach M, Petry K, Meyer H. The primary structure of porcine lactate dehydrogenase: isoenzymes M4 and H4. Hoppe Seylers Z Physiol Chem. 1977 Jan;358(1):123–127. [PubMed]
  • Sass C, Briand M, Benslimane S, Renaud M, Briand Y. Characterization of rabbit lactate dehydrogenase-M and lactate dehydrogenase-H cDNAs. Control of lactate dehydrogenase expression in rabbit muscle. J Biol Chem. 1989 Mar 5;264(7):4076–4081. [PubMed]
  • Tsujibo H, Tiano HF, Li SS. Nucleotide sequences of the cDNA and an intronless pseudogene for human lactate dehydrogenase-A isozyme. Eur J Biochem. 1985 Feb 15;147(1):9–15. [PubMed]
  • Sakai I, Sharief FS, Pan YC, Li SS. The cDNA and protein sequences of human lactate dehydrogenase B. Biochem J. 1987 Dec 15;248(3):933–936. [PMC free article] [PubMed]
  • Millan JL, Driscoll CE, LeVan KM, Goldberg E. Epitopes of human testis-specific lactate dehydrogenase deduced from a cDNA sequence. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5311–5315. [PMC free article] [PubMed]
  • Matrisian LM, Rautmann G, Magun BE, Breathnach R. Epidermal growth factor or serum stimulation of rat fibroblasts induces an elevation in mRNA levels for lactate dehydrogenase and other glycolytic enzymes. Nucleic Acids Res. 1985 Feb 11;13(3):711–726. [PMC free article] [PubMed]
  • Pan YC, Sharief FS, Okabe M, Huang S, Li SS. Amino acid sequence studies on lactate dehydrogenase C4 isozymes from mouse and rat testes. J Biol Chem. 1983 Jun 10;258(11):7005–7016. [PubMed]
  • Fukasawa KM, Li SS. Complete nucleotide sequence of the mouse lactate dehydrogenase-A functional gene: comparison of the exon-intron organization of dehydrogenase genes. Genetics. 1987 May;116(1):99–105. [PMC free article] [PubMed]
  • Hiraoka BY, Sharief FS, Yang YW, Li WH, Li SS. The cDNA and protein sequences of mouse lactate dehydrogenase B. Molecular evolution of vertebrate lactate dehydrogenase genes A (muscle), B (heart) and C (testis). Eur J Biochem. 1990 Apr 30;189(2):215–220. [PubMed]
  • Stock DW, Whitt GS. Evolutionary implications of the cDNA sequence of the single lactate dehydrogenase of a lamprey. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1799–1803. [PMC free article] [PubMed]
  • Eventoff W, Rossmann MG, Taylor SS, Torff HJ, Meyer H, Keil W, Kiltz HH. Structural adaptations of lactate dehydrogenase isozymes. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2677–2681. [PMC free article] [PubMed]
  • Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. [PubMed]
  • Edwards YH, Povey S, LeVan KM, Driscoll CE, Millan JL, Goldberg E. Locus determining the human sperm-specific lactate dehydrogenase, LDHC, is syntenic with LDHA. Dev Genet. 1987;8(4):219–232. [PubMed]
  • Li SS, Luedemann M, Sharief FS, Takano T, Deaven LL. Mapping of human lactate dehydrogenase-A, -B, and -C genes and their related sequences: the gene for LDHC is located with that for LDHA on chromosome 11. Cytogenet Cell Genet. 1988;48(1):16–18. [PubMed]
  • Thomas K, Del Mazo J, Eversole P, Bellvé A, Hiraoka Y, Li SS, Simon M. Developmental regulation of expression of the lactate dehydrogenase (LDH) multigene family during mouse spermatogenesis. Development. 1990 Jun;109(2):483–493. [PubMed]
  • Zinkham WH, Isensee H, Renwick JH. Linkage of lactate dehydrogenase B and C loci in pigeons. Science. 1969 Apr 11;164(3876):185–187. [PubMed]
  • Hendriks W, Mulders JW, Bibby MA, Slingsby C, Bloemendal H, de Jong WW. Duck lens epsilon-crystallin and lactate dehydrogenase B4 are identical: a single-copy gene product with two distinct functions. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7114–7118. [PMC free article] [PubMed]
  • Goldberg E. Immunochemical specificity of lactate dehydrogenase-X. Proc Natl Acad Sci U S A. 1971 Feb;68(2):349–352. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...