Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Dec;75(12):6187–6191. doi: 10.1073/pnas.75.12.6187

Comparison of cloned mouse alpha- and beta-globin genes: conservation of intervening sequence locations and extragenic homology.

A Leder, H I Miller, D H Hamer, J G Seidman, B Norman, M Sullivan, P Leder
PMCID: PMC393144  PMID: 282635

Abstract

We have cloned and characterized a 9.7-kilobase EcoRI fragment of mouse DNA that contains an alpha-globin gene. The gene is encoded in at least three discontinous segments of DNA interrupted by two small intervening sequences that can be visualized as R-loop structures in the electron miscroscope. The size of the gene and its small intervening sequences fits well with the known size of the alpha-globin mRNA precursor, suggesting that these intervening sequences, like those of beta-globin, are transcribed. Partial sequence analysis indicates that the larger intervening sequence interrupts the alpha-globin gene at a site exactly corresponding to that interrupted by the larger intervening sequences in both the beta-globin major and minor genes. This observation suggests that these sequences were present when the alpha- and beta-globin genes diverged in early vertebrate evolution, more than 500 million years ago. Furthermore, though alpha and betamaj genes are encoded on different chromosomes, when their sequences are compared directly by visualization of heteroduplex structures, only one 150- to 200-base-pair segment of homology is recognized. These homologous sequences are located on the 3'-flanking segments of both genes, about 1.5 kilobases from each.

Full text

PDF

Images in this article

6188Image
on p.6188
6188Image
on p.6188
6189Image
on p.6189
6191Image
on p.6191

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aloni Y., Dhar R., Laub O., Horowitz M., Khoury G. Novel mechanism for RNA maturation: the leader sequences of simian virus 40 mRNA are not transcribed adjacent to the coding sequences. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3686–3690. doi: 10.1073/pnas.74.9.3686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Berget S. M., Moore C., Sharp P. A. Spliced segments at the 5' terminus of adenovirus 2 late mRNA. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3171–3175. doi: 10.1073/pnas.74.8.3171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brack C., Tonegawa S. Variable and constant parts of the immunoglobulin light chain gene of a mouse myeloma cell are 1250 nontranslated bases apart. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5652–5656. doi: 10.1073/pnas.74.12.5652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Breathnach R., Mandel J. L., Chambon P. Ovalbumin gene is split in chicken DNA. Nature. 1977 Nov 24;270(5635):314–319. doi: 10.1038/270314a0. [DOI] [PubMed] [Google Scholar]
  6. Chow L. T., Gelinas R. E., Broker T. R., Roberts R. J. An amazing sequence arrangement at the 5' ends of adenovirus 2 messenger RNA. Cell. 1977 Sep;12(1):1–8. doi: 10.1016/0092-8674(77)90180-5. [DOI] [PubMed] [Google Scholar]
  7. Curtis P. J., Mantei N., van den Berg J., Weissmann C. Presence of a putative 15S precursor to beta-globin mRNA but not to alpha-globin mRNA in Friend cells. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3184–3188. doi: 10.1073/pnas.74.8.3184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davidson E. H., Britten R. J. Organization, transcription, and regulation in the animal genome. Q Rev Biol. 1973 Dec;48(4):565–613. doi: 10.1086/407817. [DOI] [PubMed] [Google Scholar]
  9. Doel M. T., Houghton M., Cook E. A., Carey N. H. The presence of ovalbumin mRNA coding sequences in multiple restriction fragments of chicken DNA. Nucleic Acids Res. 1977 Nov;4(11):3701–3713. doi: 10.1093/nar/4.11.3701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fantoni A., Bank A., Marks P. A. Globin composition and synthesis of hemoglobins in developing fetal mice erythroid cells. Science. 1967 Sep 15;157(3794):1327–1329. doi: 10.1126/science.157.3794.1327. [DOI] [PubMed] [Google Scholar]
  11. Gilman J. G. Rodent hemoglobin structure: a comparison of several species of mice. Ann N Y Acad Sci. 1974 Nov 29;241(0):416–433. doi: 10.1111/j.1749-6632.1974.tb21897.x. [DOI] [PubMed] [Google Scholar]
  12. Glover D. M., Hogness D. S. A novel arrangement of the 18S and 28S sequences in a repeating unit of Drosophila melanogaster rDNA. Cell. 1977 Feb;10(2):167–176. doi: 10.1016/0092-8674(77)90212-4. [DOI] [PubMed] [Google Scholar]
  13. Goodman H. M., Olson M. V., Hall B. D. Nucleotide sequence of a mutant eukaryotic gene: the yeast tyrosine-inserting ochre suppressor SUP4-o. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5453–5457. doi: 10.1073/pnas.74.12.5453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jeffreys A. J., Flavell R. A. The rabbit beta-globin gene contains a large large insert in the coding sequence. Cell. 1977 Dec;12(4):1097–1108. doi: 10.1016/0092-8674(77)90172-6. [DOI] [PubMed] [Google Scholar]
  15. Kinniburgh A. J., Mertz J. E., Ross J. The precursor of mouse beta-globin messenger RNA contains two intervening RNA sequences. Cell. 1978 Jul;14(3):681–693. doi: 10.1016/0092-8674(78)90251-9. [DOI] [PubMed] [Google Scholar]
  16. Kitchingman G. R., Lai S. P., Westphal H. Loop structures in hybrids of early RNA and the separated strands of adenovirus DNA. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4392–4395. doi: 10.1073/pnas.74.10.4392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Konkel D. A., Tilghman S. M., Leder P. The sequence of the chromosomal mouse beta-globin major gene: homologies in capping, splicing and poly(A) sites. Cell. 1978 Dec;15(4):1125–1132. doi: 10.1016/0092-8674(78)90040-5. [DOI] [PubMed] [Google Scholar]
  18. Lai E. C., Woo S. L., Dugaiczyk A., Catterall J. F., O'Malley B. W. The ovalbumin gene: structural sequences in native chicken DNA are not contiguous. Proc Natl Acad Sci U S A. 1978 May;75(5):2205–2209. doi: 10.1073/pnas.75.5.2205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leder P., Tilghman S. M., Tiemeier D. C., Polsky F. I., Seidman J. G., Edgell M. H., Enquist L. W., Leder A., Norman B. The cloning of mouse globin and surrounding gene sequences in bacteriophage lambda. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):915–920. doi: 10.1101/sqb.1978.042.01.093. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Polsky F., Edgell M. H., Seidman J. G., Leder P. High capacity gel preparative electrophoresis for purification of fragments of genomic DNA. Anal Biochem. 1978 Jul 1;87(2):397–410. doi: 10.1016/0003-2697(78)90689-9. [DOI] [PubMed] [Google Scholar]
  22. Popp R. A., Bailiff E. G. Sequence of amino acids in the major and minor chains of the diffuse hemoglobin from BALB-c mice. Biochim Biophys Acta. 1973 Mar 23;303(1):61–67. doi: 10.1016/0005-2795(73)90148-7. [DOI] [PubMed] [Google Scholar]
  23. Popp R. A. Hemoglobins of mice: sequence and possible ambiguity at one position of the alpha chain. J Mol Biol. 1967 Jul 14;27(1):9–16. doi: 10.1016/0022-2836(67)90347-6. [DOI] [PubMed] [Google Scholar]
  24. Ross J. A precursor of globin messenger RNA. J Mol Biol. 1976 Sep 15;106(2):403–420. doi: 10.1016/0022-2836(76)90093-0. [DOI] [PubMed] [Google Scholar]
  25. Rougeon F., Mach B. Cloning and amplification of alpha and beta mouse globin gene sequences synthesised in vitro. Gene. 1977 May;1(3-4):229–239. doi: 10.1016/0378-1119(77)90047-6. [DOI] [PubMed] [Google Scholar]
  26. Russell E. S., McFarland E. C. Genetics of mouse hemoglobins. Ann N Y Acad Sci. 1974 Nov 29;241(0):25–38. doi: 10.1111/j.1749-6632.1974.tb21864.x. [DOI] [PubMed] [Google Scholar]
  27. Smith K., Lingrel J. B. Sequence organization of the beta-globin mRNA precursor. Nucleic Acids Res. 1978 Sep;5(9):3295–3301. doi: 10.1093/nar/5.9.3295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. Tiemeier D. C., Tilghman S. M., Leder P. Purification and cloning of a mouse ribosomal gene fragment in coliphage lambda. Gene. 1977;2(3-4):173–191. doi: 10.1016/0378-1119(77)90016-6. [DOI] [PubMed] [Google Scholar]
  30. Tiemeier D. C., Tilghman S. M., Polsky F. I., Seidman J. G., Leder A., Edgell M. H., Leder P. A comparison of two cloned mouse beta-globin genes and their surrounding and intervening sequences. Cell. 1978 Jun;14(2):237–245. doi: 10.1016/0092-8674(78)90110-1. [DOI] [PubMed] [Google Scholar]
  31. Tiemer D., Enquist L., Leder P. Improved derivative of a phage lambda EK2 vector for cloning recombinant DNA. Nature. 1976 Oct 7;263(5577):526–527. doi: 10.1038/263526a0. [DOI] [PubMed] [Google Scholar]
  32. Tilghman S. M., Curtis P. J., Tiemeier D. C., Leder P., Weissmann C. The intervening sequence of a mouse beta-globin gene is transcribed within the 15S beta-globin mRNA precursor. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1309–1313. doi: 10.1073/pnas.75.3.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Tilghman S. M., Tiemeier D. C., Polsky F., Edgell M. H., Seidman J. G., Leder A., Enquist L. W., Norman B., Leder P. Cloning specific segments of the mammalian genome: bacteriophage lambda containing mouse globin and surrounding gene sequences. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4406–4410. doi: 10.1073/pnas.74.10.4406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tilghman S. M., Tiemeier D. C., Seidman J. G., Peterlin B. M., Sullivan M., Maizel J. V., Leder P. Intervening sequence of DNA identified in the structural portion of a mouse beta-globin gene. Proc Natl Acad Sci U S A. 1978 Feb;75(2):725–729. doi: 10.1073/pnas.75.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Valenzuela P., Venegas A., Weinberg F., Bishop R., Rutter W. J. Structure of yeast phenylalanine-tRNA genes: an intervening DNA segment within the region coding for the tRNA. Proc Natl Acad Sci U S A. 1978 Jan;75(1):190–194. doi: 10.1073/pnas.75.1.190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weinstock R., Sweet R., Weiss M., Cedar H., Axel R. Intragenic DNA spacers interrupt the ovalbumin gene. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1299–1303. doi: 10.1073/pnas.75.3.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wellauer P. K., Dawid I. B. The structural organization of ribosomal DNA in Drosophila melanogaster. Cell. 1977 Feb;10(2):193–212. doi: 10.1016/0092-8674(77)90214-8. [DOI] [PubMed] [Google Scholar]
  38. White R. L., Hogness D. S. R loop mapping of the 18S and 28S sequences in the long and short repeating units of Drosophila melanogaster rDNA. Cell. 1977 Feb;10(2):177–192. doi: 10.1016/0092-8674(77)90213-6. [DOI] [PubMed] [Google Scholar]
  39. van den Berg J., van Ooyen A., Mantei N., Schamböck A., Grosveld G., Flavell R. A., Weissmann C. Comparison of cloned rabbit and mouse beta-globin genes showing strong evolutionary divergence of two homologous pairs of introns. Nature. 1978 Nov 2;276(5683):37–44. doi: 10.1038/276037a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES