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. 1984 Jun 11;12(11):4469–4479. doi: 10.1093/nar/12.11.4469

Human fetal globin DNA sequences suggest novel conversion event.

C J Stoeckert Jr, F S Collins, S M Weissman
PMCID: PMC318851  PMID: 6330670

Abstract

DNA sequencing studies of two recently cloned human A gamma globin alleles has revealed a number of base differences which are clustered in the large intron (IVS-2). One allele has a previously undescribed IVS-2 sequence. Most of the allelic differences can be explained as resulting from a gene conversion event involving G gamma as a donor. A novel feature of this event is that three G gamma-like regions occur interspersed among unconverted areas of the A gamma gene. We propose that an alternating purine-pyrimidine run which is located between two of the converted sites is the initiation site of the conversion event. Consistent with models of gene conversion, this poly (purine-pyrimidine) tract has single-stranded characteristics in supercoiled plasmids as assayed by S1-nuclease.

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Selected References

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  1. Arnott S., Chandrasekaran R., Birdsall D. L., Leslie A. G., Ratliff R. L. Left-handed DNA helices. Nature. 1980 Feb 21;283(5749):743–745. doi: 10.1038/283743a0. [DOI] [PubMed] [Google Scholar]
  2. Bentley D. L., Rabbitts T. H. Evolution of immunoglobulin V genes: evidence indicating that recently duplicated human V kappa sequences have diverged by gene conversion. Cell. 1983 Jan;32(1):181–189. doi: 10.1016/0092-8674(83)90508-1. [DOI] [PubMed] [Google Scholar]
  3. Bianchi M., DasGupta C., Radding C. M. Synapsis and the formation of paranemic joints by E. coli RecA protein. Cell. 1983 Oct;34(3):931–939. doi: 10.1016/0092-8674(83)90550-0. [DOI] [PubMed] [Google Scholar]
  4. Cockerill P. N., Goodwin G. H. Demonstration of an S1-nuclease sensitive site near the human beta-globin gene, and its protection by HMG 1 and 2. Biochem Biophys Res Commun. 1983 Apr 29;112(2):547–554. doi: 10.1016/0006-291x(83)91499-7. [DOI] [PubMed] [Google Scholar]
  5. Deininger P. L. Random subcloning of sonicated DNA: application to shotgun DNA sequence analysis. Anal Biochem. 1983 Feb 15;129(1):216–223. doi: 10.1016/0003-2697(83)90072-6. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Egel R. Intergenic conversion and reiterated genes. Nature. 1981 Mar 19;290(5803):191–192. doi: 10.1038/290191a0. [DOI] [PubMed] [Google Scholar]
  8. Grosveld F. G., Dahl H. H., de Boer E., Flavell R. A. Isolation of beta-globin-related genes from a human cosmid library. Gene. 1981 Apr;13(3):227–237. doi: 10.1016/0378-1119(81)90028-7. [DOI] [PubMed] [Google Scholar]
  9. Jackson J. A., Fink G. R. Gene conversion between duplicated genetic elements in yeast. Nature. 1981 Jul 23;292(5821):306–311. doi: 10.1038/292306a0. [DOI] [PubMed] [Google Scholar]
  10. Jeffreys A. J. DNA sequence variants in the G gamma-, A gamma-, delta- and beta-globin genes of man. Cell. 1979 Sep;18(1):1–10. doi: 10.1016/0092-8674(79)90348-9. [DOI] [PubMed] [Google Scholar]
  11. Klein H. L., Petes T. D. Intrachromosomal gene conversion in yeast. Nature. 1981 Jan 15;289(5794):144–148. doi: 10.1038/289144a0. [DOI] [PubMed] [Google Scholar]
  12. Kourilsky P. Genetic exchanges between partially homologous nucleotide sequences: possible implications for multigene families. Biochimie. 1983 Feb;65(2):85–93. doi: 10.1016/s0300-9084(83)80178-3. [DOI] [PubMed] [Google Scholar]
  13. Kłysik J., Stirdivant S. M., Wells R. D. Left-handed DNA. Cloning, characterization, and instability of inserts containing different lengths of (dC-dG) in Escherichia coli. J Biol Chem. 1982 Sep 10;257(17):10152–10158. [PubMed] [Google Scholar]
  14. 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]
  15. Liskay R. M., Stachelek J. L. Evidence for intrachromosomal gene conversion in cultured mouse cells. Cell. 1983 Nov;35(1):157–165. doi: 10.1016/0092-8674(83)90218-0. [DOI] [PubMed] [Google Scholar]
  16. Martin S. L., Vincent K. A., Wilson A. C. Rise and fall of the delta globin gene. J Mol Biol. 1983 Mar 15;164(4):513–528. doi: 10.1016/0022-2836(83)90048-7. [DOI] [PubMed] [Google Scholar]
  17. Meselson M. S., Radding C. M. A general model for genetic recombination. Proc Natl Acad Sci U S A. 1975 Jan;72(1):358–361. doi: 10.1073/pnas.72.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Messing J., Vieira J. A new pair of M13 vectors for selecting either DNA strand of double-digest restriction fragments. Gene. 1982 Oct;19(3):269–276. doi: 10.1016/0378-1119(82)90016-6. [DOI] [PubMed] [Google Scholar]
  19. Michelson A. M., Orkin S. H. Boundaries of gene conversion within the duplicated human alpha-globin genes. Concerted evolution by segmental recombination. J Biol Chem. 1983 Dec 25;258(24):15245–15254. [PubMed] [Google Scholar]
  20. Miller L. K., Cooke B. E., Fried M. Fate of mismatched base-pair regions in polyoma heteroduplex DNA during infection of mouse cells. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3073–3077. doi: 10.1073/pnas.73.9.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nordheim A., Rich A. Negatively supercoiled simian virus 40 DNA contains Z-DNA segments within transcriptional enhancer sequences. Nature. 1983 Jun 23;303(5919):674–679. doi: 10.1038/303674a0. [DOI] [PubMed] [Google Scholar]
  22. Ollo R., Rougeon F. Gene conversion and polymorphism: generation of mouse immunoglobulin gamma 2a chain alleles by differential gene conversion by gamma 2b chain gene. Cell. 1983 Feb;32(2):515–523. doi: 10.1016/0092-8674(83)90471-3. [DOI] [PubMed] [Google Scholar]
  23. Orkin S. H., Antonarakis S. E., Kazazian H. H., Jr Polymorphism and molecular pathology of the human beta-globin gene. Prog Hematol. 1983;13:49–73. [PubMed] [Google Scholar]
  24. Pease L. R., Schulze D. H., Pfaffenbach G. M., Nathenson S. G. Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the major histocompatibility complex. Proc Natl Acad Sci U S A. 1983 Jan;80(1):242–246. doi: 10.1073/pnas.80.1.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Petes T., Fink G. R. Gene conversion between repeated genes. Nature. 1982 Nov 18;300(5889):216–217. doi: 10.1038/300216a0. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Rossignol J. L., Paquette N., Nicolas A. Aberrant 4:4 asci, disparity in the direction of conversion, and frequencies of conversion in Ascobolus immersus. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 2):1343–1352. doi: 10.1101/sqb.1979.043.01.153. [DOI] [PubMed] [Google Scholar]
  28. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shen S. H., Slightom J. L., Smithies O. A history of the human fetal globin gene duplication. Cell. 1981 Oct;26(2 Pt 2):191–203. doi: 10.1016/0092-8674(81)90302-0. [DOI] [PubMed] [Google Scholar]
  30. Singleton C. K., Klysik J., Stirdivant S. M., Wells R. D. Left-handed Z-DNA is induced by supercoiling in physiological ionic conditions. Nature. 1982 Sep 23;299(5881):312–316. doi: 10.1038/299312a0. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Stringer J. R. DNA sequence homology and chromosomal deletion at a site of SV40 DNA integration. Nature. 1982 Mar 25;296(5855):363–366. doi: 10.1038/296363a0. [DOI] [PubMed] [Google Scholar]
  33. Szostak J. W., Orr-Weaver T. L., Rothstein R. J., Stahl F. W. The double-strand-break repair model for recombination. Cell. 1983 May;33(1):25–35. doi: 10.1016/0092-8674(83)90331-8. [DOI] [PubMed] [Google Scholar]
  34. Weiss E. H., Mellor A., Golden L., Fahrner K., Simpson E., Hurst J., Flavell R. A. The structure of a mutant H-2 gene suggests that the generation of polymorphism in H-2 genes may occur by gene conversion-like events. Nature. 1983 Feb 24;301(5902):671–674. doi: 10.1038/301671a0. [DOI] [PubMed] [Google Scholar]
  35. Wilson J. H. Genetic analysis of host range mutant viruses suggests an uncoating defect in simian virus 40-resistant monkey cells. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3503–3507. doi: 10.1073/pnas.74.8.3503. [DOI] [PMC free article] [PubMed] [Google Scholar]

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