Abstract
Hybridization kinetic analyses with synthetic DNA indicate that there are only two to three copies of the κ constant region gene per haploid genome. This result lends weight to the argument that the immunoglobulin light chain is encoded by more than one continuous gene sequence.
Keywords: gene reiteration, hybridization, synthetic DNA, mRNA
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Selected References
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- Ando T. A nuclease specific for heat-denatured DNA in isolated from a product of Aspergillus oryzae. Biochim Biophys Acta. 1966 Jan 18;114(1):158–168. doi: 10.1016/0005-2787(66)90263-2. [DOI] [PubMed] [Google Scholar]
- Appella E. Amino acid sequences of two mouse immunoglobulin lambda chains. Proc Natl Acad Sci U S A. 1971 Mar;68(3):590–594. doi: 10.1073/pnas.68.3.590. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Aviv H., Packman S., Swan D., Ross J., Leder P. In vitro synthesis of DNA complementary to mRNA derived from a light chain-producing myeloma tumour. Nat New Biol. 1973 Feb 7;241(110):174–176. doi: 10.1038/newbio241174a0. [DOI] [PubMed] [Google Scholar]
- Bernardini A., Tonegawa S. Hybridization studies with an antibody heavy chain mRNA. FEBS Lett. 1974 Apr 15;41(1):73–77. doi: 10.1016/0014-5793(74)80957-9. [DOI] [PubMed] [Google Scholar]
- Birnstiel M. L., Sells B. H., Purdom I. F. Kinetic complexity of RNA molecules. J Mol Biol. 1972 Jan 14;63(1):21–39. doi: 10.1016/0022-2836(72)90519-0. [DOI] [PubMed] [Google Scholar]
- Bishop J. O. The effect of genetic complexity on the time-course of ribonucleic acid-deoxyribonucleic acid hybridization. Biochem J. 1969 Aug;113(5):805–811. doi: 10.1042/bj1130805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brenner S., Milstein C. Origin of antibody variation. Nature. 1966 Jul 16;211(5046):242–243. doi: 10.1038/211242a0. [DOI] [PubMed] [Google Scholar]
- Britten R. J., Kohne D. E. Repeated sequences in DNA. Hundreds of thousands of copies of DNA sequences have been incorporated into the genomes of higher organisms. Science. 1968 Aug 9;161(3841):529–540. doi: 10.1126/science.161.3841.529. [DOI] [PubMed] [Google Scholar]
- Brownlee G. G., Cartwright E. M., Cowan N. J., Jarvis J. M., Milstein C. Purification and sequence of messenger RNA for immunoglobulin light chains. Nat New Biol. 1973 Aug 22;244(138):236–240. doi: 10.1038/newbio244236a0. [DOI] [PubMed] [Google Scholar]
- Brownlee G. G., Harrison T. M., Mathews M. B., Milstein C. Translation of messenger RNA for immunoglobulin light chains in a cell-free system from Krebs II ascites cells. FEBS Lett. 1972 Jun 15;23(2):244–248. doi: 10.1016/0014-5793(72)80352-1. [DOI] [PubMed] [Google Scholar]
- Cohn M. The take-home lesson--1971. Ann N Y Acad Sci. 1971 Dec 31;190:529–584. doi: 10.1111/j.1749-6632.1971.tb13562.x. [DOI] [PubMed] [Google Scholar]
- Delovitch T. L., Baglioni C. Estimation of light-chain gene reiteration of mouse immunoglobulin by DNA-RNA hybridization. Proc Natl Acad Sci U S A. 1973 Jan;70(1):173–178. doi: 10.1073/pnas.70.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dreyer W. J., Bennett J. C. The molecular basis of antibody formation: a paradox. Proc Natl Acad Sci U S A. 1965 Sep;54(3):864–869. doi: 10.1073/pnas.54.3.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edelman G. M., Gally J. A. Somatic recombination of duplicated genes: an hypothesis on the origin of antibody diversity. Proc Natl Acad Sci U S A. 1967 Feb;57(2):353–358. doi: 10.1073/pnas.57.2.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Efron D., Marcus A. Efficient synthesis of rabbit globin in a cell-free system from wheat embryo. FEBS Lett. 1973 Jun 15;33(1):23–27. doi: 10.1016/0014-5793(73)80150-4. [DOI] [PubMed] [Google Scholar]
- Gally J. A., Edelman G. M. Somatic translocation of antibody genes. Nature. 1970 Jul 25;227(5256):341–348. doi: 10.1038/227341a0. [DOI] [PubMed] [Google Scholar]
- Gray W. R., Dreyer W. J., Hood L. Mechanism of antibody synthesis: size differences between mouse kappa chains. Science. 1967 Jan 27;155(3761):465–467. doi: 10.1126/science.155.3761.465. [DOI] [PubMed] [Google Scholar]
- Hood L. E. Two genes, one polypeptide chain--fact or fiction? Fed Proc. 1972 Jan-Feb;31(1):177–187. [PubMed] [Google Scholar]
- Hood L., Talmage D. W. Mechanism of antibody diversity: germ line basis for variability. Science. 1970 Apr 17;168(3929):325–334. doi: 10.1126/science.168.3929.325. [DOI] [PubMed] [Google Scholar]
- Jerne N. K. The somatic generation of immune recognition. Eur J Immunol. 1971 Jan;1(1):1–9. doi: 10.1002/eji.1830010102. [DOI] [PubMed] [Google Scholar]
- Kunkel H. G., Natvig J. B., Joslin F. G. A "Lepore" type of hybrid gamma-globulin. Proc Natl Acad Sci U S A. 1969 Jan;62(1):144–149. doi: 10.1073/pnas.62.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LEDERBERG J. Genes and antibodies. Science. 1959 Jun 19;129(3364):1649–1653. doi: 10.1126/science.129.3364.1649. [DOI] [PubMed] [Google Scholar]
- Leder P., Ross J., Gielen J., Packman S., Ikawa Y., Aviv H., Swan D. Regulated expression of mammalian genes: globin and immunoglobulin as model systems. Cold Spring Harb Symp Quant Biol. 1974;38:753–761. doi: 10.1101/sqb.1974.038.01.080. [DOI] [PubMed] [Google Scholar]
- Lieberman R., Potter M. Close linkage in genes controlling gamma-A and gamma-G heavy chain structure in BALB/c mice. J Mol Biol. 1966 Jul;18(3):516–528. doi: 10.1016/s0022-2836(66)80040-2. [DOI] [PubMed] [Google Scholar]
- Mach B., Faust C., Vassalli P. Purification of 14S messenger RNA of immunoglobulin light chain that codes for a possible light-chain precursor. Proc Natl Acad Sci U S A. 1973 Feb;70(2):451–455. doi: 10.1073/pnas.70.2.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mage R. G., Young-Cooper G. O., Alexander C. Genetic control of variable and constant regions of immunoglobulin heavy chains. Nat New Biol. 1971 Mar 10;230(10):63–64. doi: 10.1038/newbio230063a0. [DOI] [PubMed] [Google Scholar]
- Milstein C., Brownlee G. G., Harrison T. M., Mathews M. B. A possible precursor of immunoglobulin light chains. Nat New Biol. 1972 Sep 27;239(91):117–120. doi: 10.1038/newbio239117a0. [DOI] [PubMed] [Google Scholar]
- Packman S., Aviv H., Ross J., Leder P. A comparison of globin genes in duck reticulocytes and liver cells. Biochem Biophys Res Commun. 1972 Nov 1;49(3):813–819. doi: 10.1016/0006-291x(72)90483-4. [DOI] [PubMed] [Google Scholar]
- Premkumar E., Shoyab M., Williamson A. R. Germ line basis for antibody diversity: immunoglobulin VH-and CH-gene frequencies measured by DNA-RNA hybridization. Proc Natl Acad Sci U S A. 1974 Jan;71(1):99–103. doi: 10.1073/pnas.71.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rabbitts T. H., Bishop J. O., Milstein C., Brownlee G. G. Comparative hybridization studies iwth an immunoglobulin light chain mRNA fraction and non-immunoglobulin mRNA of mouse. FEBS Lett. 1974 Mar 15;40(1):157–160. doi: 10.1016/0014-5793(74)80917-8. [DOI] [PubMed] [Google Scholar]
- Roberts B. E., Paterson B. M. Efficient translation of tobacco mosaic virus RNA and rabbit globin 9S RNA in a cell-free system from commercial wheat germ. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2330–2334. doi: 10.1073/pnas.70.8.2330. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross J., Aviv H., Leder P. Characterization of synthetic rabbit globin DNA. Arch Biochem Biophys. 1973 Oct;158(2):494–502. doi: 10.1016/0003-9861(73)90541-9. [DOI] [PubMed] [Google Scholar]
- Ross J., Aviv H., Scolnick E., Leder P. In vitro synthesis of DNA complementary to purified rabbit globin mRNA (RNA-dependent DNA polymerase-reticulocyte-hemoglobin-density gradient centrifugation-oligo(dT) primer). Proc Natl Acad Sci U S A. 1972 Jan;69(1):264–268. doi: 10.1073/pnas.69.1.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ross J., Ikawa Y., Leder P. Globin messenger-RNA induction during erythroid differentiation of cultured leukemia cells. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3620–3623. doi: 10.1073/pnas.69.12.3620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SMITHIES O. GAMMA-GLOBULIN VARIABILITY: A GENETIC HYPOTHESIS. Nature. 1963 Sep 28;199:1231–1236. doi: 10.1038/1991231a0. [DOI] [PubMed] [Google Scholar]
- Schechter I. Biologically and chemically pure mRNA coding for a mouse immunoglobulin L-chain prepared with the aid of antibodies and immobilized oligothymidine. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2256–2260. doi: 10.1073/pnas.70.8.2256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith G. P. Mouse immunoglobulin kappa chain MPC 11: extra amino-terminal residues. Science. 1973 Sep 7;181(4103):941–943. doi: 10.1126/science.181.4103.941. [DOI] [PubMed] [Google Scholar]
- Smith M., Stavnezer J., Huang R. C., Gurdon J. B., Lane C. D. Letter: Translation of messenger RNA for mouse immunoglobulin light chains in living frog oocytes. J Mol Biol. 1973 Nov 5;80(3):553–557. doi: 10.1016/0022-2836(73)90422-1. [DOI] [PubMed] [Google Scholar]
- Smithies O. Antibody variability. Somatic recombination between the elements of "antibody gene pairs" may explain antibody variability. Science. 1967 Jul 21;157(3786):267–273. doi: 10.1126/science.157.3786.267. [DOI] [PubMed] [Google Scholar]
- Smithies O. Pathways through networks of branched DNA. Science. 1970 Aug 28;169(3948):882–883. doi: 10.1126/science.169.3948.882. [DOI] [PubMed] [Google Scholar]
- Stavnezer J., Huang R. C. Synthesis of a mouse immunoglobulin light chain in a rabbit reticulocyte cell-free system. Nat New Biol. 1971 Apr 7;230(14):172–176. doi: 10.1038/newbio230172a0. [DOI] [PubMed] [Google Scholar]
- Staynov D. Z., Pinder J. C., Gratzer W. B. Molecular weight determination of nucleic acids by gel electrophoresis in non-aqueous solution. Nat New Biol. 1972 Jan 26;235(56):108–110. doi: 10.1038/newbio235108a0. [DOI] [PubMed] [Google Scholar]
- Stevens R. H., Williamson A. R. Specific IgG mRNA molecules from myeloma cells in heterogeneous nuclear and cytoplasmic RNA containing poly-A. Nature. 1972 Sep 15;239(5368):143–146. doi: 10.1038/239143a0. [DOI] [PubMed] [Google Scholar]
- Storb U. Evidence for multiple immunoglobulin genes. Biochem Biophys Res Commun. 1974 Mar 15;57(1):31–38. doi: 10.1016/s0006-291x(74)80353-0. [DOI] [PubMed] [Google Scholar]
- Storb U. Quantitation of immunoglobulin genes by nucleic acid hybridization with RNA from myeloma and spleen microsomes. J Immunol. 1972 Mar;108(3):755–764. [PubMed] [Google Scholar]
- Sutton W. D. A crude nuclease preparation suitable for use in DNA reassociation experiments. Biochim Biophys Acta. 1971 Jul 29;240(4):522–531. doi: 10.1016/0005-2787(71)90709-x. [DOI] [PubMed] [Google Scholar]
- Swan D., Aviv H., Leder P. Purification and properties of biologically active messenger RNA for a myeloma light chain. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1967–1971. doi: 10.1073/pnas.69.7.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Szilard L. THE MOLECULAR BASIS OF ANTIBODY FORMATION. Proc Natl Acad Sci U S A. 1960 Mar;46(3):293–302. doi: 10.1073/pnas.46.3.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tonegawa S., Baldi I. Electrophoretically homogeneous myeloma light chain mRNA and its translation in vitro. Biochem Biophys Res Commun. 1973 Mar 5;51(1):81–87. doi: 10.1016/0006-291x(73)90510-x. [DOI] [PubMed] [Google Scholar]
- Tonegawa S., Bernardini A., Weimann B. J., Steinberg C. Reiteration frequency of antibody genes. Studies with k-chain mRNA. FEBS Lett. 1974 Mar 15;40(1):92–96. doi: 10.1016/0014-5793(74)80901-4. [DOI] [PubMed] [Google Scholar]
- Tosi S. L., Dubiski S., Mage R. G. Distribution of allotypic specificities A1, A2, A14, and A15 among immunoglobulin G molecules. J Immunol. 1970 Mar;104(3):641–647. [PubMed] [Google Scholar]
- Wang A. C., Wang I. Y., McCormick J. N., Fudenberg H. H. The identity of light chains of monoclonal IgG and monoclonal IgM in one patient. Immunochemistry. 1969 May;6(3):451–459. doi: 10.1016/0019-2791(69)90301-2. [DOI] [PubMed] [Google Scholar]