Abstract
Five closely related immunoglobulin VH genes (subgroup II) were compared by sequencing of several kb of DNA. In three of the genes homology greater than 75% was found along an area of 4 kb that includes the coding region. The homology in flanking regions is only slightly lower than that in the coding sequences. Two other genes, which are located on the same EcoRI fragment, show high homology to the first three genes in the coding and immediately flanking regions. In more distant flanking regions no homology is found with the first three genes. This indicates that their evolutionary history differs from that of the other three genes. A region of simple DNA sequence composed of repetitive TCC and TCA elements was found at a distance of approximately 380 bp upstream from the initiator ATG of these VH genes. This region is the site where the two sets of genes abruptly start to diverge. The structure of the simple DNA sequence in the various VH genes suggests that it may be involved in gene interaction. We propose that both simple DNA sequences and homology in flanking regions serve a function in the correction of VH genes, which seem to be rather free to diverge and drift into pseudogenes. A correction mechanism may help this gene family to maintain its two major features, multiplicity and diversity.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baltimore D. Gene conversion: some implications for immunoglobulin genes. Cell. 1981 Jun;24(3):592–594. doi: 10.1016/0092-8674(81)90082-9. [DOI] [PubMed] [Google Scholar]
- Bentley D. L., Rabbitts T. H. Human immunoglobulin variable region genes--DNA sequences of two V kappa genes and a pseudogene. Nature. 1980 Dec 25;288(5792):730–733. doi: 10.1038/288730a0. [DOI] [PubMed] [Google Scholar]
- Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
- Bernard O., Hozumi N., Tonegawa S. Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell. 1978 Dec;15(4):1133–1144. doi: 10.1016/0092-8674(78)90041-7. [DOI] [PubMed] [Google Scholar]
- Bolivar F., Rodriguez R. L., Greene P. J., Betlach M. C., Heyneker H. L., Boyer H. W., Crosa J. H., Falkow S. Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. Gene. 1977;2(2):95–113. [PubMed] [Google Scholar]
- Bothwell A. L., Paskind M., Reth M., Imanishi-Kari T., Rajewsky K., Baltimore D. Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region. Cell. 1981 Jun;24(3):625–637. doi: 10.1016/0092-8674(81)90089-1. [DOI] [PubMed] [Google Scholar]
- Crews S., Griffin J., Huang H., Calame K., Hood L. A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody. Cell. 1981 Jul;25(1):59–66. doi: 10.1016/0092-8674(81)90231-2. [DOI] [PubMed] [Google Scholar]
- Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
- Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
- Givol D., Zakut R., Effron K., Rechavi G., Ram D., Cohen J. B. Diversity of germ-line immunoglobulin VH genes. Nature. 1981 Jul 30;292(5822):426–430. doi: 10.1038/292426a0. [DOI] [PubMed] [Google Scholar]
- Gough N. M., Bernard O. Sequences of the joining region genes for immunoglobulin heavy chains and their role in generation of antibody diversity. Proc Natl Acad Sci U S A. 1981 Jan;78(1):509–513. doi: 10.1073/pnas.78.1.509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grunstein M., Hogness D. S. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3961–3965. doi: 10.1073/pnas.72.10.3961. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hood L., Campbell J. H., Elgin S. C. The organization, expression, and evolution of antibody genes and other multigene families. Annu Rev Genet. 1975;9:305–353. doi: 10.1146/annurev.ge.09.120175.001513. [DOI] [PubMed] [Google Scholar]
- Kedes L. H. Histone genes and histone messengers. Annu Rev Biochem. 1979;48:837–870. doi: 10.1146/annurev.bi.48.070179.004201. [DOI] [PubMed] [Google Scholar]
- Kim S., Davis M., Sinn E., Patten P., Hood L. Antibody diversity: somatic hypermutation of rearranged VH genes. Cell. 1981 Dec;27(3 Pt 2):573–581. doi: 10.1016/0092-8674(81)90399-8. [DOI] [PubMed] [Google Scholar]
- Lauer J., Shen C. K., Maniatis T. The chromosomal arrangement of human alpha-like globin genes: sequence homology and alpha-globin gene deletions. Cell. 1980 May;20(1):119–130. doi: 10.1016/0092-8674(80)90240-8. [DOI] [PubMed] [Google Scholar]
- Liebhaber S. A., Goossens M., Kan Y. W. Homology and concerted evolution at the alpha 1 and alpha 2 loci of human alpha-globin. Nature. 1981 Mar 5;290(5801):26–29. doi: 10.1038/290026a0. [DOI] [PubMed] [Google Scholar]
- Max E. E., Seidman J. G., Leder P. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3450–3454. doi: 10.1073/pnas.76.7.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishioka Y., Leder P. Organization and complete sequence of identical embryonic and plasmacytoma kappa V-region genes. J Biol Chem. 1980 Apr 25;255(8):3691–3694. [PubMed] [Google Scholar]
- Proudfoot N. J., Maniatis T. The structure of a human alpha-globin pseudogene and its relationship to alpha-globin gene duplication. Cell. 1980 Sep;21(2):537–544. doi: 10.1016/0092-8674(80)90491-2. [DOI] [PubMed] [Google Scholar]
- Rabbitts T. H., Matthyssens G., Hamlyn P. H. Contribution of immunoglobulin heavy-chain variable-region genes to antibody diversity. Nature. 1980 Mar 20;284(5753):238–243. doi: 10.1038/284238a0. [DOI] [PubMed] [Google Scholar]
- Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
- Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. doi: 10.1038/286676a0. [DOI] [PubMed] [Google Scholar]
- Sanger F., Coulson A. R. The use of thin acrylamide gels for DNA sequencing. FEBS Lett. 1978 Mar 1;87(1):107–110. doi: 10.1016/0014-5793(78)80145-8. [DOI] [PubMed] [Google Scholar]
- Schaffner W., Kunz G., Daetwyler H., Telford J., Smith H. O., Birnstiel M. L. Genes and spacers of cloned sea urchin histone DNA analyzed by sequencing. Cell. 1978 Jul;14(3):655–671. doi: 10.1016/0092-8674(78)90249-0. [DOI] [PubMed] [Google Scholar]
- Seidman J. G., Leder A., Nau M., Norman B., Leder P. Antibody diversity. Science. 1978 Oct 6;202(4363):11–17. doi: 10.1126/science.99815. [DOI] [PubMed] [Google Scholar]
- Slightom J. L., Blechl A. E., Smithies O. Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell. 1980 Oct;21(3):627–638. doi: 10.1016/0092-8674(80)90426-2. [DOI] [PubMed] [Google Scholar]
- Smith D. R., Calvo J. M. Nucleotide sequence of the E coli gene coding for dihydrofolate reductase. Nucleic Acids Res. 1980 May 24;8(10):2255–2274. doi: 10.1093/nar/8.10.2255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith H. O., Birnstiel M. L. A simple method for DNA restriction site mapping. Nucleic Acids Res. 1976 Sep;3(9):2387–2398. doi: 10.1093/nar/3.9.2387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sodergren E. J., Fox M. S. Effects of DNA sequence non-homology on formation of bacteriophage lambda recombinants. J Mol Biol. 1979 Jun 5;130(4):357–377. doi: 10.1016/0022-2836(79)90428-5. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Sures I., Lowry J., Kedes L. H. The DNA sequence of sea urchin (S. purpuratus) H2A, H2B and H3 histone coding and spacer regions. Cell. 1978 Nov;15(3):1033–1044. doi: 10.1016/0092-8674(78)90287-8. [DOI] [PubMed] [Google Scholar]
- Weigert M., Perry R., Kelley D., Hunkapiller T., Schilling J., Hood L. The joining of V and J gene segments creates antibody diversity. Nature. 1980 Jan 31;283(5746):497–499. doi: 10.1038/283497a0. [DOI] [PubMed] [Google Scholar]
- Wellauer P. K., Dawid I. B., Brown D. D., Reeder R. H. The molecular basis for length heterogeneity in ribosomal DNA from Xenopus laevis. J Mol Biol. 1976 Aug 25;105(4):461–486. doi: 10.1016/0022-2836(76)90229-1. [DOI] [PubMed] [Google Scholar]
- Zakut R., Cohen J., Givol D. Cloning and sequence of the cDNA corresponding to the variable region of immunoglobulin heavy chain MPC11. Nucleic Acids Res. 1980 Aug 25;8(16):3591–3601. doi: 10.1093/nar/8.16.3591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zakut R., Givol D., Mory Y. Y. Structure of immunoglobulin gamma 2b heavy chain gene cloned from mouse embryo gene library. Nucleic Acids Res. 1980 Feb 11;8(3):453–466. doi: 10.1093/nar/8.3.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmer E. A., Martin S. L., Beverley S. M., Kan Y. W., Wilson A. C. Rapid duplication and loss of genes coding for the alpha chains of hemoglobin. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2158–2162. doi: 10.1073/pnas.77.4.2158. [DOI] [PMC free article] [PubMed] [Google Scholar]