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. 1981 Aug;78(8):4694–4698. doi: 10.1073/pnas.78.8.4694

alpha-Fetoprotein and albumin genes are in tandem in the mouse genome.

R S Ingram, R W Scott, S M Tilghman
PMCID: PMC320229  PMID: 6170978

Abstract

The urine alpha-fetoprotein (AFP) and serum albumin genes most probably arose in evolution as the consequence of a duplication of a common ancestral gene. They have both been previously mapped to chromosome 5 in the mouse. We now have evidence that these genes are closely linked. By using a unique copy DNA probe derived from previously cloned AFP 5' flanking DNA, a recombinant DNA phage has been isolated, from a bacteriophage DNA library, that contains sequences flanking the 5' end of the AFP gene and the 3' end of the albumin gene. Restriction endonuclease mapping and DNA sequence determination of the recombinant phage and comparison to total genomic DNA confirmed that the genes are in tandem, 13.5 kilobase pairs apart, with the albumin gene to the 5' side of the AFP gene. Thus, they are transcribed from the same strand of DNA.

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Selected References

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  1. Abelev G. I. Alpha-fetoprotein as a marker of embryo-specific differentiations in normal and tumor tissues. Transplant Rev. 1974;20(0):3–37. doi: 10.1111/j.1600-065x.1974.tb00139.x. [DOI] [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. Bernards R., Kooter J. M., Flavell R. A. Physical mapping of the globin gene deletion in (delta beta (0)) -thalassaemia. Gene. 1979 Jul;6(3):265–280. doi: 10.1016/0378-1119(79)90062-3. [DOI] [PubMed] [Google Scholar]
  4. Blattner F. R., Williams B. G., Blechl A. E., Denniston-Thompson K., Faber H. E., Furlong L., Grunwald D. J., Kiefer D. O., Moore D. D., Schumm J. W. Charon phages: safer derivatives of bacteriophage lambda for DNA cloning. Science. 1977 Apr 8;196(4286):161–169. doi: 10.1126/science.847462. [DOI] [PubMed] [Google Scholar]
  5. Buehler B. A. Hereditary disorders of albumin synthesis. Ann Clin Lab Sci. 1978 Jul-Aug;8(4):283–286. [PubMed] [Google Scholar]
  6. D'Eustachio P., Ingram R. S., Tilghman S. M., Ruddle F. H. Murine alpha-fetoprotein and albumin: two evolutionarily linked proteins encoded on the same mouse chromosome. Somatic Cell Genet. 1981 May;7(3):289–294. doi: 10.1007/BF01538854. [DOI] [PubMed] [Google Scholar]
  7. D'Eustachio P., Pravtcheva D., Marcu K., Ruddle F. H. Chromosomal location of the structural gene cluster encoding murine immunoglobulin heavy chains. J Exp Med. 1980 Jun 1;151(6):1545–1550. doi: 10.1084/jem.151.6.1545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deisseroth A., Nienhuis A., Turner P., Velez R., Anderson W. F., Ruddle F., Lawrence J., Creagan R., Kucherlapati R. Localization of the human alpha-globin structural gene to chromosome 16 in somatic cell hybrids by molecular hybridization assay. Cell. 1977 Sep;12(1):205–218. doi: 10.1016/0092-8674(77)90198-2. [DOI] [PubMed] [Google Scholar]
  9. Dodgson J. B., Strommer J., Engel J. D. Isolation of the chicken beta-globin gene and a linked embryonic beta-like globin gene from a chicken DNA recombinant library. Cell. 1979 Aug;17(4):879–887. doi: 10.1016/0092-8674(79)90328-3. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Fritsch E. F., Lawn R. M., Maniatis T. Characterisation of deletions which affect the expression of fetal globin genes in man. Nature. 1979 Jun 14;279(5714):598–603. doi: 10.1038/279598a0. [DOI] [PubMed] [Google Scholar]
  12. Gitlin D., Perricelli A., Gitlin J. D. The presence of serum alpha-fetoprotein in sharks and its synthesis by fetal gastrointestinal tract and liver. Comp Biochem Physiol B. 1973 Oct 15;46(2):207–215. doi: 10.1016/0305-0491(73)90311-8. [DOI] [PubMed] [Google Scholar]
  13. Gorin M. B., Cooper D. L., Eiferman F., van de Rijn P., Tilghman S. M. The evolution of alpha-fetoprotein and albumin. I. A comparison of the primary amino acid sequences of mammalian alpha-fetoprotein and albumin. J Biol Chem. 1981 Feb 25;256(4):1954–1959. [PubMed] [Google Scholar]
  14. Gorin M. B., Tilghman S. M. Structure of the alpha-fetoprotein gene in the mouse. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1351–1355. doi: 10.1073/pnas.77.3.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gusella J., Varsanyi-Breiner A., Kao F. T., Jones C., Puck T. T., Keys C., Orkin S., Housman D. Precise localization of human beta-globin gene complex on chromosome 11. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5239–5242. doi: 10.1073/pnas.76.10.5239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Heilig R., Perrin F., Gannon F., Mandel J. L., Chambon P. The ovalbumin gene family: structure of the X gene and evolution of duplicated split genes. Cell. 1980 Jul;20(3):625–637. doi: 10.1016/0092-8674(80)90309-8. [DOI] [PubMed] [Google Scholar]
  17. Hughes S. H., Stubblefield E., Payvar F., Engel J. D., Dodgson J. B., Spector D., Cordell B., Schimke R. T., Varmus H. E. Gene localization by chromosome fractionation: globin genes are on at least two chromosomes and three estrogen-inducible genes are on three chromosomes. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1348–1352. doi: 10.1073/pnas.76.3.1348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Innis M. A., Miller D. L. alpha-Fetoprotein gene expression. Partial DNA sequence and COOH-terminal homology to albumin. J Biol Chem. 1980 Oct 10;255(19):8994–8996. [PubMed] [Google Scholar]
  19. Jahn C. L., Hutchison C. A., 3rd, Phillips S. J., Weaver S., Haigwood N. L., Voliva C. F., Edgell M. H. DNA sequence organization of the beta-globin complex in the BALB/c mouse. Cell. 1980 Aug;21(1):159–168. doi: 10.1016/0092-8674(80)90123-3. [DOI] [PubMed] [Google Scholar]
  20. Jeffreys A. J., Craig I. W., Francke U. Localisation of the G gamma-, A gamma-, delta- and beta-globin genes on the short arm of human chromosome 11. Nature. 1979 Oct 18;281(5732):606–608. doi: 10.1038/281606a0. [DOI] [PubMed] [Google Scholar]
  21. Jeffreys A. J., Wilson V., Wood D., Simons J. P., Kay R. M., Williams J. G. Linkage of adult alpha- and beta-globin genes in X. laevis and gene duplication by tetraploidization. Cell. 1980 Sep;21(2):555–564. doi: 10.1016/0092-8674(80)90493-6. [DOI] [PubMed] [Google Scholar]
  22. Jones C. W., Kafatos F. C. Structure, organization and evolution of developmentally regulated chorion genes in a silkmoth. Cell. 1980 Dec;22(3):855–867. doi: 10.1016/0092-8674(80)90562-0. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Kioussis D., Eiferman F., van de Rijn P., Gorin M. B., Ingram R. S., Tilghman S. M. The evolution of alpha-fetoprotein and albumin. II. The structures of the alpha-fetoprotein and albumin genes in the mouse. J Biol Chem. 1981 Feb 25;256(4):1960–1967. [PubMed] [Google Scholar]
  25. Kioussis D., Hamilton R., Hanson R. W., Tilghman S. M., Taylor J. M. Construction and cloning of rat albumin structural gene sequences. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4370–4374. doi: 10.1073/pnas.76.9.4370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lacy E., Hardison R. C., Quon D., Maniatis T. The linkage arrangement of four rabbit beta-like globin genes. Cell. 1979 Dec;18(4):1273–1283. doi: 10.1016/0092-8674(79)90238-1. [DOI] [PubMed] [Google Scholar]
  27. Lerner M. R., Boyle J. A., Mount S. M., Wolin S. L., Steitz J. A. Are snRNPs involved in splicing? Nature. 1980 Jan 10;283(5743):220–224. doi: 10.1038/283220a0. [DOI] [PubMed] [Google Scholar]
  28. Liao W. S., Hamilton R. W., Taylor J. M. Amino acid sequence homology between rat alpha-fetoprotein and albumin at the COOH-terminal regions. J Biol Chem. 1980 Sep 10;255(17):8046–8049. [PubMed] [Google Scholar]
  29. Lifton R. P., Goldberg M. L., Karp R. W., Hogness D. S. The organization of the histone genes in Drosophila melanogaster: functional and evolutionary implications. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):1047–1051. doi: 10.1101/sqb.1978.042.01.105. [DOI] [PubMed] [Google Scholar]
  30. Lindgren J., Vaheri A., Ruoslahti E. Identification and isolation of a foetoprotein in the chicken. Differentiation. 1974 Aug;2(4):233–236. doi: 10.1111/j.1432-0436.1974.tb00356.x. [DOI] [PubMed] [Google Scholar]
  31. Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
  32. Maniatis T., Jeffrey A., Kleid D. G. Nucleotide sequence of the rightward operator of phage lambda. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1184–1188. doi: 10.1073/pnas.72.3.1184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. Nagase S., Shimamune K., Shumiya S. Albumin-deficient rat mutant. Science. 1979 Aug 10;205(4406):590–591. doi: 10.1126/science.451621. [DOI] [PubMed] [Google Scholar]
  35. Ruoslahti E., Engvall E. Immunological crossreaction between alpha-fetoprotein and albumin. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4641–4644. doi: 10.1073/pnas.73.12.4641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ruoslahti E., Seppälä M. alpha-Fetoprotein in cancer and fetal development. Adv Cancer Res. 1979;29:275–346. doi: 10.1016/s0065-230x(08)60849-0. [DOI] [PubMed] [Google Scholar]
  37. Ruoslahti E., Terry W. D. alpha foetoprotein and serum albumin show sequence homology. Nature. 1976 Apr 29;260(5554):804–805. doi: 10.1038/260804a0. [DOI] [PubMed] [Google Scholar]
  38. Sala-Trepat J. M., Dever J., Sargent T. D., Thomas K., Sell S., Bonner J. Changes in expression of albumin and alpha-fetoprotein genes during rat liver development and neoplasia. Biochemistry. 1979 May 29;18(11):2167–2178. doi: 10.1021/bi00578a006. [DOI] [PubMed] [Google Scholar]
  39. Sargent T. D., Yang M., Bonner J. Nucleotide sequence of cloned rat serum albumin messenger RNA. Proc Natl Acad Sci U S A. 1981 Jan;78(1):243–246. doi: 10.1073/pnas.78.1.243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schibler U., Marcu K. B., Perry R. P. The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells. Cell. 1978 Dec;15(4):1495–1509. doi: 10.1016/0092-8674(78)90072-7. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. Swan D., D'Eustachio P., Leinwand L., Seidman J., Keithley D., Ruddle F. H. Chromosomal assignment of the mouse kappa light chain genes. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2735–2739. doi: 10.1073/pnas.76.6.2735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. 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]
  44. Tuan D., Biro P. A., deRiel J. K., Lazarus H., Forget B. G. Restriction endonuclease mapping of the human gamma globin gene loci. Nucleic Acids Res. 1979 Jun 11;6(7):2519–2544. doi: 10.1093/nar/6.7.2519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wahl G. M., Stern M., Stark G. R. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. doi: 10.1073/pnas.76.8.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Wu C., Wong Y. C., Elgin S. C. The chromatin structure of specific genes: II. Disruption of chromatin structure during gene activity. Cell. 1979 Apr;16(4):807–814. doi: 10.1016/0092-8674(79)90096-5. [DOI] [PubMed] [Google Scholar]

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