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EMBO J. Jul 1988; 7(7): 1979–1988.
PMCID: PMC454470

Complete structure and organization of immunoglobulin heavy chain constant region genes in a phylogenetically primitive vertebrate.

Abstract

Immunoglobulin (Ig) gene organization in Heterodontus francisci (horned shark), a phylogenetically primitive vertebrate, is unique. Homologous Ig heavy chain variable (VH) and constant region (CH) specific probes were used to screen a spleen cDNA library constructed in lambda gt11. Both secretory (SEC) and transmembrane (TM) cDNA clones were recovered; the latter were identified by a negative selection strategy. The complete sequence of the CH portion of a Heterodontus genomic DNA-lambda clone also was determined. The sequences of the individual CH genes differ from each other in all exons. When compared to mammalian prototypes, similarities in exon and intron organization as well as conservation of sequences involved with differential splicing of SEC and TM mRNA indicate that Heterodontus heavy chain genes are of the mu type, although intron lengths are uniformly longer in Heterodontus. Heterodontus genes are not associated, however, with the family of DNA sequences that have been implicated in heavy chain class switching in mammals. Spleen cDNA library screening and RNA blot analyses indicate that mRNAs encoding TM Ig are exceedingly rare. The relationship between this quantitative difference and the distribution of polyadenylation signal sequences suggests that regulation of Ig gene expression in Heterodontus may be highly dependent on position effects.

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Selected References

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  • Alt FW, Bothwell AL, Knapp M, Siden E, Mather E, Koshland M, Baltimore D. Synthesis of secreted and membrane-bound immunoglobulin mu heavy chains is directed by mRNAs that differ at their 3' ends. Cell. 1980 Jun;20(2):293–301. [PubMed]
  • Chirgwin JM, Przybyla AE, MacDonald RJ, Rutter WJ. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. [PubMed]
  • Clem LW, Small PA., Jr Phylogeny of immunoglobulin structure and function. I. Immunoglobulins of the lemon shark. J Exp Med. 1967 May 1;125(5):893–920. [PMC free article] [PubMed]
  • Dahan A, Reynaud CA, Weill JC. Nucleotide sequence of the constant region of a chicken mu heavy chain immunoglobulin mRNA. Nucleic Acids Res. 1983 Aug 25;11(16):5381–5389. [PMC free article] [PubMed]
  • Early P, Rogers J, Davis M, Calame K, Bond M, Wall R, Hood L. Two mRNAs can be produced from a single immunoglobulin mu gene by alternative RNA processing pathways. Cell. 1980 Jun;20(2):313–319. [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Galli G, Guise JW, McDevitt MA, Tucker PW, Nevins JR. Relative position and strengths of poly(A) sites as well as transcription termination are critical to membrane versus secreted mu-chain expression during B-cell development. Genes Dev. 1987 Jul;1(5):471–481. [PubMed]
  • Goldberg GI, Vanin EF, Zrolka AM, Blattner FR. Sequence of the gene for the constant region of the mu chain of Balb/c mouse immunoglobulin. Gene. 1981 Oct;15(1):33–42. [PubMed]
  • Hinds KR, Litman GW. Major reorganization of immunoglobulin VH segmental elements during vertebrate evolution. Nature. 1986 Apr 10;320(6062):546–549. [PubMed]
  • Honjo T. Immunoglobulin genes. Annu Rev Immunol. 1983;1:499–528. [PubMed]
  • Kehry M, Sibley C, Fuhrman J, Schilling J, Hood LE. Amino acid sequence of a mouse immunoglobulin mu chain. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2932–2936. [PMC free article] [PubMed]
  • Kokubu F, Hinds K, Litman R, Shamblott MJ, Litman GW. Extensive families of constant region genes in a phylogenetically primitive vertebrate indicate an additional level of immunoglobulin complexity. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5868–5872. [PMC free article] [PubMed]
  • Law R, Kuwabara MD, Briskin M, Fasel N, Hermanson G, Sigman DS, Wall R. Protein-binding site at the immunoglobulin mu membrane polyadenylylation signal: possible role in transcription termination. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9160–9164. [PMC free article] [PubMed]
  • Litman GW, Berger L, Murphy K, Litman R, Hinds K, Erickson BW. Immunoglobulin VH gene structure and diversity in Heterodontus, a phylogenetically primitive shark. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2082–2086. [PMC free article] [PubMed]
  • Marcu KB, Banerji J, Penncavage NA, Lang R, Arnheim N. 5' flanking region of immunoglobulin heavy chain constant region genes displays length heterogeneity in germlines of inbred mouse strains. Cell. 1980 Nov;22(1 Pt 1):187–196. [PubMed]
  • McCumber LJ, Clem LW. A comparative study of J chain structure and stoichiometry in human and nurse shark IgM. Immunochemistry. 1976 Jun;13(6):479–484. [PubMed]
  • McGuire KL, Duncan WR, Tucker PW. Phylogenetic conservation of immunoglobulin heavy chains: direct comparison of hamster and mouse Cmu genes. Nucleic Acids Res. 1985 Aug 12;13(15):5611–5628. [PMC free article] [PubMed]
  • Nikaido T, Nakai S, Honjo T. Switch region of immunoglobulin Cmu gene is composed of simple tandem repetitive sequences. Nature. 1981 Aug 27;292(5826):845–848. [PubMed]
  • Perry RP, Kelley DE. Immunoglobulin messenger RNAs in murine cell lines that have characteristics of immature B lymphocytes. Cell. 1979 Dec;18(4):1333–1339. [PubMed]
  • Peterson ML, Perry RP. Regulated production of mu m and mu s mRNA requires linkage of the poly(A) addition sites and is dependent on the length of the mu s-mu m intron. Proc Natl Acad Sci U S A. 1986 Dec;83(23):8883–8887. [PMC free article] [PubMed]
  • Reth M, Petrac E, Wiese P, Lobel L, Alt FW. Activation of V kappa gene rearrangement in pre-B cells follows the expression of membrane-bound immunoglobulin heavy chains. EMBO J. 1987 Nov;6(11):3299–3305. [PMC free article] [PubMed]
  • Rogers J, Wall R. Immunoglobulin RNA rearrangements in B lymphocyte differentiation. Adv Immunol. 1984;35:39–59. [PubMed]
  • Rogers J, Early P, Carter C, Calame K, Bond M, Hood L, Wall R. Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin mu chain. Cell. 1980 Jun;20(2):303–312. [PubMed]
  • Sakano H, Rogers JH, Hüppi K, Brack C, Traunecker A, Maki R, Wall R, Tonegawa S. Domains and the hinge region of an immunoglobulin heavy chain are encoded in separate DNA segments. Nature. 1979 Feb 22;277(5698):627–633. [PubMed]
  • Sakoyama Y, Yaoita Y, Honjo T. Immunoglobulin switch region-like sequences in Drosophila melanogaster. Nucleic Acids Res. 1982 Jul 24;10(14):4203–4214. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Schwager J, Mikoryak CA, Steiner LA. Amino acid sequence of heavy chain from Xenopus laevis IgM deduced from cDNA sequence: implications for evolution of immunoglobulin domains. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2245–2249. [PMC free article] [PubMed]
  • Shimizu A, Takahashi N, Yaoita Y, Honjo T. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Cell. 1982 Mar;28(3):499–506. [PubMed]
  • Sitia R, Neuberger MS, Milstein C. Regulation of membrane IgM expression in secretory B cells: translational and post-translational events. EMBO J. 1987 Dec 20;6(13):3969–3977. [PMC free article] [PubMed]
  • Takahashi N, Ueda S, Obata M, Nikaido T, Nakai S, Honjo T. Structure of human immunoglobulin gamma genes: implications for evolution of a gene family. Cell. 1982 Jun;29(2):671–679. [PubMed]
  • Tsurushita N, Korn LJ. Effects of intron length on differential processing of mouse mu heavy-chain mRNA. Mol Cell Biol. 1987 Jul;7(7):2602–2605. [PMC free article] [PubMed]
  • Tsurushita N, Ho L, Korn LJ. Nuclear factors in B lymphoma enhance splicing of mouse membrane-bound mu mRNA in Xenopus oocytes. Science. 1988 Jan 29;239(4839):494–497. [PubMed]
  • Liu CP, Tucker PW, Mushinski JF, Blattner FR. Mapping of heavy chain genes for mouse immunoglobulins M and D. Science. 1980 Sep 19;209(4463):1348–1353. [PubMed]
  • Wickens M, Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984 Nov 30;226(4678):1045–1051. [PubMed]
  • Young RA, Davis RW. Efficient isolation of genes by using antibody probes. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1194–1198. [PMC free article] [PubMed]

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