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. 1986 Feb 25;14(4):1883–1902. doi: 10.1093/nar/14.4.1883

Evolution of the casein multigene family: conserved sequences in the 5' flanking and exon regions.

L Y Yu-Lee, L Richter-Mann, C H Couch, A F Stewart, A G Mackinlay, J M Rosen
PMCID: PMC339580  PMID: 3952000

Abstract

The rat alpha- and bovine alpha s1-casein genes have been isolated and their 5' sequences determined. The rat alpha-, beta-, gamma- and bovine alpha s1-casein genes contain similar 5' exon arrangements in which the 5' noncoding, signal peptide and casein kinase phosphorylation sequences are each encoded by separate exons. These findings support the hypothesis that during evolution, the family of casein genes arose by a process involving exon recruitment followed by intragenic and intergenic duplication of a primordial gene. Several highly conserved regions in the first 200 base pairs of the 5' flanking DNA have been identified. Additional sequence homology extending up to 550 base pairs upstream of the CAP site has been found between the rat alpha- and bovine alpha s1-casein sequences. Unexpectedly, the 5' flanking promoter regions are conserved to a greater extent than both the entire mature coding and intron regions of these genes. These conserved 5' flanking sequences may contain potential cis regulatory elements which are responsible for the coordinate expression of the functionally-related casein genes during mammary gland development.

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Selected References

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

  1. Blackburn D. E., Hobbs A. A., Rosen J. M. Rat beta casein cDNA: sequence analysis and evolutionary comparisons. Nucleic Acids Res. 1982 Apr 10;10(7):2295–2307. doi: 10.1093/nar/10.7.2295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  3. Calos M. P., Miller J. H. Transposable elements. Cell. 1980 Jul;20(3):579–595. doi: 10.1016/0092-8674(80)90305-0. [DOI] [PubMed] [Google Scholar]
  4. Campbell S. M., Rosen J. M., Hennighausen L. G., Strech-Jurk U., Sippel A. E. Comparison of the whey acidic protein genes of the rat and mouse. Nucleic Acids Res. 1984 Nov 26;12(22):8685–8697. doi: 10.1093/nar/12.22.8685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cato A. C., Geisse S., Wenz M., Westphal H. M., Beato M. The nucleotide sequences recognized by the glucocorticoid receptor in the rabbit uteroglobin gene region are located far upstream from the initiation of transcription. EMBO J. 1984 Dec 1;3(12):2771–2778. doi: 10.1002/j.1460-2075.1984.tb02208.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Charnay P., Treisman R., Mellon P., Chao M., Axel R., Maniatis T. Differences in human alpha- and beta-globin gene expression in mouse erythroleukemia cells: the role of intragenic sequences. Cell. 1984 Aug;38(1):251–263. doi: 10.1016/0092-8674(84)90547-6. [DOI] [PubMed] [Google Scholar]
  7. Concino M., Goldman R. A., Caruthers M. H., Weinmann R. Point mutations of the adenovirus major late promoter with different transcriptional efficiencies in vitro. J Biol Chem. 1983 Jul 10;258(13):8493–8496. [PubMed] [Google Scholar]
  8. Davidson E. H., Jacobs H. T., Britten R. J. Very short repeats and coordinate induction of genes. Nature. 1983 Feb 10;301(5900):468–470. doi: 10.1038/301468a0. [DOI] [PubMed] [Google Scholar]
  9. Dierks P., van Ooyen A., Mantei N., Weissmann C. DNA sequences preceding the rabbit beta-globin gene are required for formation in mouse L cells of beta-globin RNA with the correct 5' terminus. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1411–1415. doi: 10.1073/pnas.78.3.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Donahue T. F., Daves R. S., Lucchini G., Fink G. R. A short nucleotide sequence required for regulation of HIS4 by the general control system of yeast. Cell. 1983 Jan;32(1):89–98. doi: 10.1016/0092-8674(83)90499-3. [DOI] [PubMed] [Google Scholar]
  11. Dynan W. S., Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983 Nov;35(1):79–87. doi: 10.1016/0092-8674(83)90210-6. [DOI] [PubMed] [Google Scholar]
  12. Gilbert W. Why genes in pieces? Nature. 1978 Feb 9;271(5645):501–501. doi: 10.1038/271501a0. [DOI] [PubMed] [Google Scholar]
  13. Grosschedl R., Baltimore D. Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell. 1985 Jul;41(3):885–897. doi: 10.1016/s0092-8674(85)80069-6. [DOI] [PubMed] [Google Scholar]
  14. Gupta P., Rosen J. M., D'Eustachio P., Ruddle F. H. Localization of the casein gene family to a single mouse chromosome. J Cell Biol. 1982 Apr;93(1):199–204. doi: 10.1083/jcb.93.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Guyette W. A., Matusik R. J., Rosen J. M. Prolactin-mediated transcriptional and post-transcriptional control of casein gene expression. Cell. 1979 Aug;17(4):1013–1023. doi: 10.1016/0092-8674(79)90340-4. [DOI] [PubMed] [Google Scholar]
  16. Hall L., Laird J. E., Craig R. K. Nucleotide sequence determination of guinea-pig casein B mRNA reveals homology with bovine and rat alpha s1 caseins and conservation of the non-coding regions of the mRNA. Biochem J. 1984 Sep 15;222(3):561–570. doi: 10.1042/bj2220561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hall L., Laird J. E., Pascall J. C., Craig R. K. Guinea-pig casein A cDNA. Nucleotide sequence analysis and comparison of the deduced protein sequence with that of bovine alpha s2 casein. Eur J Biochem. 1984 Feb 1;138(3):585–589. doi: 10.1111/j.1432-1033.1984.tb07954.x. [DOI] [PubMed] [Google Scholar]
  18. Hamada H., Petrino M. G., Kakunaga T., Seidman M., Stollar B. D. Characterization of genomic poly(dT-dG).poly(dC-dA) sequences: structure, organization, and conformation. Mol Cell Biol. 1984 Dec;4(12):2610–2621. doi: 10.1128/mcb.4.12.2610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hamada H., Seidman M., Howard B. H., Gorman C. M. Enhanced gene expression by the poly(dT-dG).poly(dC-dA) sequence. Mol Cell Biol. 1984 Dec;4(12):2622–2630. doi: 10.1128/mcb.4.12.2622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hayes T. E., Dixon J. E. Z-DNA in the rat somatostatin gene. J Biol Chem. 1985 Jul 5;260(13):8145–8156. [PubMed] [Google Scholar]
  21. Hennighausen L. G., Sippel A. E. Characterization and cloning of the mRNAs specific for the lactating mouse mammary gland. Eur J Biochem. 1982 Jun 15;125(1):131–141. doi: 10.1111/j.1432-1033.1982.tb06660.x. [DOI] [PubMed] [Google Scholar]
  22. Hobbs A. A., Richards D. A., Kessler D. J., Rosen J. M. Complex hormonal regulation of rat casein gene expression. J Biol Chem. 1982 Apr 10;257(7):3598–3605. [PubMed] [Google Scholar]
  23. Hobbs A. A., Rosen J. M. Sequence of rat alpha- and gamma-casein mRNAs: evolutionary comparison of the calcium-dependent rat casein multigene family. Nucleic Acids Res. 1982 Dec 20;10(24):8079–8098. doi: 10.1093/nar/10.24.8079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Inouye S., Soberon X., Franceschini T., Nakamura K., Itakura K., Inouye M. Role of positive charge on the amino-terminal region of the signal peptide in protein secretion across the membrane. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3438–3441. doi: 10.1073/pnas.79.11.3438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Johnson M. L., Levy J., Supowit S. C., Yu-Lee L. Y., Rosen J. M. Tissue- and cell-specific casein gene expression. II. Relationship to site-specific DNA methylation. J Biol Chem. 1983 Sep 10;258(17):10805–10811. [PubMed] [Google Scholar]
  26. Jones W. K., Yu-Lee L. Y., Clift S. M., Brown T. L., Rosen J. M. The rat casein multigene family. Fine structure and evolution of the beta-casein gene. J Biol Chem. 1985 Jun 10;260(11):7042–7050. [PubMed] [Google Scholar]
  27. Jost J. P., Seldran M., Geiser M. Preferential binding of estrogen-receptor complex to a region containing the estrogen-dependent hypomethylation site preceding the chicken vitellogenin II gene. Proc Natl Acad Sci U S A. 1984 Jan;81(2):429–433. doi: 10.1073/pnas.81.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kafatos F. C., Jones C. W., Efstratiadis A. Determination of nucleic acid sequence homologies and relative concentrations by a dot hybridization procedure. Nucleic Acids Res. 1979 Nov 24;7(6):1541–1552. doi: 10.1093/nar/7.6.1541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Karin M., Haslinger A., Holtgreve H., Richards R. I., Krauter P., Westphal H. M., Beato M. Characterization of DNA sequences through which cadmium and glucocorticoid hormones induce human metallothionein-IIA gene. Nature. 1984 Apr 5;308(5959):513–519. doi: 10.1038/308513a0. [DOI] [PubMed] [Google Scholar]
  30. Larsen A., Weintraub H. An altered DNA conformation detected by S1 nuclease occurs at specific regions in active chick globin chromatin. Cell. 1982 Jun;29(2):609–622. doi: 10.1016/0092-8674(82)90177-5. [DOI] [PubMed] [Google Scholar]
  31. Maurer R. A. Selective binding of the estradiol receptor to a region at least one kilobase upstream from the rat prolactin gene. DNA. 1985 Feb;4(1):1–9. doi: 10.1089/dna.1985.4.1. [DOI] [PubMed] [Google Scholar]
  32. Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
  33. McKnight S. L. Functional relationships between transcriptional control signals of the thymidine kinase gene of herpes simplex virus. Cell. 1982 Dec;31(2 Pt 1):355–365. doi: 10.1016/0092-8674(82)90129-5. [DOI] [PubMed] [Google Scholar]
  34. McKnight S. L., Kingsbury R. C., Spence A., Smith M. The distal transcription signals of the herpesvirus tk gene share a common hexanucleotide control sequence. Cell. 1984 May;37(1):253–262. doi: 10.1016/0092-8674(84)90321-0. [DOI] [PubMed] [Google Scholar]
  35. Mercier J. C., Grosclaude F., Ribadeau-Dumas B. Structure primaire de la caséine s1 -bovine. Séquence complète. Eur J Biochem. 1971 Nov 11;23(1):41–51. doi: 10.1111/j.1432-1033.1971.tb01590.x. [DOI] [PubMed] [Google Scholar]
  36. Merrill G. F., Hauschka S. D., McKnight S. L. tk Enzyme expression in differentiating muscle cells is regulated through an internal segment of the cellular tk gene. Mol Cell Biol. 1984 Sep;4(9):1777–1784. doi: 10.1128/mcb.4.9.1777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Messing J. New M13 vectors for cloning. Methods Enzymol. 1983;101:20–78. doi: 10.1016/0076-6879(83)01005-8. [DOI] [PubMed] [Google Scholar]
  38. Miyata T., Hayashida H., Kikuno R., Hasegawa M., Kobayashi M., Koike K. Molecular clock of silent substitution: at least six-fold preponderance of silent changes in mitochondrial genes over those in nuclear genes. J Mol Evol. 1982;19(1):28–35. doi: 10.1007/BF02100221. [DOI] [PubMed] [Google Scholar]
  39. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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]
  41. Ohno S., Emori Y., Imajoh S., Kawasaki H., Kisaragi M., Suzuki K. Evolutionary origin of a calcium-dependent protease by fusion of genes for a thiol protease and a calcium-binding protein? Nature. 1984 Dec 6;312(5994):566–570. doi: 10.1038/312566a0. [DOI] [PubMed] [Google Scholar]
  42. Payvar F., DeFranco D., Firestone G. L., Edgar B., Wrange O., Okret S., Gustafsson J. A., Yamamoto K. R. Sequence-specific binding of glucocorticoid receptor to MTV DNA at sites within and upstream of the transcribed region. Cell. 1983 Dec;35(2 Pt 1):381–392. doi: 10.1016/0092-8674(83)90171-x. [DOI] [PubMed] [Google Scholar]
  43. Pelham H. R. A regulatory upstream promoter element in the Drosophila hsp 70 heat-shock gene. Cell. 1982 Sep;30(2):517–528. doi: 10.1016/0092-8674(82)90249-5. [DOI] [PubMed] [Google Scholar]
  44. Qasba P. K., Safaya S. K. Similarity of the nucleotide sequences of rat alpha-lactalbumin and chicken lysozyme genes. Nature. 1984 Mar 22;308(5957):377–380. doi: 10.1038/308377a0. [DOI] [PubMed] [Google Scholar]
  45. Renkawitz R., Schütz G., von der Ahe D., Beato M. Sequences in the promoter region of the chicken lysozyme gene required for steroid regulation and receptor binding. Cell. 1984 Jun;37(2):503–510. doi: 10.1016/0092-8674(84)90380-5. [DOI] [PubMed] [Google Scholar]
  46. Rosen J. M., O'Neal D. L., McHugh J. E., Comstock J. P. Progesterone-mediated inhibition of casein mRNA and polysomal casein synthesis in the rat mammary gland during pregnancy. Biochemistry. 1978 Jan 24;17(2):290–297. doi: 10.1021/bi00595a016. [DOI] [PubMed] [Google Scholar]
  47. Ruppert S., Scherer G., Schütz G. Recent gene conversion involving bovine vasopressin and oxytocin precursor genes suggested by nucleotide sequence. Nature. 1984 Apr 5;308(5959):554–557. doi: 10.1038/308554a0. [DOI] [PubMed] [Google Scholar]
  48. Sargent T. D., Wu J. R., Sala-Trepat J. M., Wallace R. B., Reyes A. A., Bonner J. The rat serum albumin gene: analysis of cloned sequences. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3256–3260. doi: 10.1073/pnas.76.7.3256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Scheidereit C., Geisse S., Westphal H. M., Beato M. The glucocorticoid receptor binds to defined nucleotide sequences near the promoter of mouse mammary tumour virus. Nature. 1983 Aug 25;304(5928):749–752. doi: 10.1038/304749a0. [DOI] [PubMed] [Google Scholar]
  50. Searle P. F., Davison B. L., Stuart G. W., Wilkie T. M., Norstedt G., Palmiter R. D. Regulation, linkage, and sequence of mouse metallothionein I and II genes. Mol Cell Biol. 1984 Jul;4(7):1221–1230. doi: 10.1128/mcb.4.7.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Slater E. P., Rabenau O., Karin M., Baxter J. D., Beato M. Glucocorticoid receptor binding and activation of a heterologous promoter by dexamethasone by the first intron of the human growth hormone gene. Mol Cell Biol. 1985 Nov;5(11):2984–2992. doi: 10.1128/mcb.5.11.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Sleigh R. W., Sculley T. B., Mackinlay A. G. The binding of beta-casein to hydroxyapatite: the effect of phosphate content and location. J Dairy Res. 1979 Apr;46(2):337–342. doi: 10.1017/s0022029900017271. [DOI] [PubMed] [Google Scholar]
  53. Soares M. B., Schon E., Henderson A., Karathanasis S. K., Cate R., Zeitlin S., Chirgwin J., Efstratiadis A. RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon. Mol Cell Biol. 1985 Aug;5(8):2090–2103. doi: 10.1128/mcb.5.8.2090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Staden R. An interactive graphics program for comparing and aligning nucleic acid and amino acid sequences. Nucleic Acids Res. 1982 May 11;10(9):2951–2961. doi: 10.1093/nar/10.9.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Stewart A. F., Willis I. M., Mackinlay A. G. Nucleotide sequences of bovine alpha S1- and kappa-casein cDNAs. Nucleic Acids Res. 1984 May 11;12(9):3895–3907. doi: 10.1093/nar/12.9.3895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Suwa Y., Mizukami Y., Sogawa K., Fujii-Kuriyama Y. Gene structure of a major form of phenobarbital-inducible cytochrome P-450 in rat liver. J Biol Chem. 1985 Jul 5;260(13):7980–7984. [PubMed] [Google Scholar]
  57. Südhof T. C., Goldstein J. L., Brown M. S., Russell D. W. The LDL receptor gene: a mosaic of exons shared with different proteins. Science. 1985 May 17;228(4701):815–822. doi: 10.1126/science.2988123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Topper Y. J. Multiple hormone interactions in the development of mammary gland in vitro. Recent Prog Horm Res. 1970;26:287–308. doi: 10.1016/b978-0-12-571126-5.50011-x. [DOI] [PubMed] [Google Scholar]
  59. Walter P., Blobel G. Purification of a membrane-associated protein complex required for protein translocation across the endoplasmic reticulum. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7112–7116. doi: 10.1073/pnas.77.12.7112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Williams L., McDonald C., Higgins S. Sequence organisation of rat seminal vesicle F gene: location of transcriptional start point and sequence comparison with six other androgen-regulated genes. Nucleic Acids Res. 1985 Feb 11;13(3):659–672. doi: 10.1093/nar/13.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Yu-Lee L. Y., Rosen J. M. The rat casein multigene family. I. Fine structure of the gamma-casein gene. J Biol Chem. 1983 Sep 10;258(17):10794–10804. [PubMed] [Google Scholar]
  62. von der Ahe D., Janich S., Scheidereit C., Renkawitz R., Schütz G., Beato M. Glucocorticoid and progesterone receptors bind to the same sites in two hormonally regulated promoters. Nature. 1985 Feb 21;313(6004):706–709. doi: 10.1038/313706a0. [DOI] [PubMed] [Google Scholar]

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