Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1985 Apr;5(4):768–779. doi: 10.1128/mcb.5.4.768

Two distinct families of human and bovine interferon-alpha genes are coordinately expressed and encode functional polypeptides.

D J Capon, H M Shepard, D V Goeddel
PMCID: PMC366781  PMID: 2985969

Abstract

The classical human interferon-alpha (HuIFN-alpha) gene family is estimated to consist of 15 or more nonallelic members which encode proteins sharing greater than 77% amino acid sequence homology. Low-stringency hybridization with a HuIFN-alpha cDNA probe permitted the isolation of two distinct classes of bovine IFN-alpha genes. The first subfamily (class I) is more closely related to the known HuIFN-alpha genes than to the second subfamily (class II) of bovine IFN-alpha genes. Extensive analysis of the human genome has revealed a HuIFN-alpha gene subfamily corresponding to the class II bovine IFN-alpha genes. The class I human and bovine IFN-alpha genes encode mature IFN polypeptides of 165 to 166 amino acids, whereas the class II IFN-alpha genes encode 172 amino acid proteins. Expression in Escherichia coli of members of both gene subfamilies results in polypeptides having potent antiviral activity. In contrast to previous studies which found no evidence of class II IFN-alpha protein or mRNA expression, we demonstrate that the class I and class II IFN-alpha genes are coordinately induced in response to viral infection.

Full text

PDF
771

Images in this article

772Image
on p.772
774Image
on p.774

Selected References

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

  1. Allen G., Fantes K. H. A family of structural genes for human lymphoblastoid (leukocyte-type) interferon. Nature. 1980 Oct 2;287(5781):408–411. doi: 10.1038/287408a0. [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. Blin N., Stafford D. W. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976 Sep;3(9):2303–2308. doi: 10.1093/nar/3.9.2303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brack C., Nagata S., Mantei N., Weissmann C. Molecular analysis of the human interferon-alpha gene family. Gene. 1981 Dec;15(4):379–394. doi: 10.1016/0378-1119(81)90181-5. [DOI] [PubMed] [Google Scholar]
  5. Cantell K., Hirvonen S., Kauppinen H. L., Myllylä G. Production of interferon in human leukocytes from normal donors with the use of Sendai virus. Methods Enzymol. 1981;78(Pt A):29–38. doi: 10.1016/0076-6879(81)78094-7. [DOI] [PubMed] [Google Scholar]
  6. Crea R., Horn T. Synthesis of oligonucleotides on cellulose by a phosphotriester method. Nucleic Acids Res. 1980 May 24;8(10):2331–2348. doi: 10.1093/nar/8.10.2331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Degrave W., Derynck R., Tavernier J., Haegeman G., Fiers W. Nucleotide sequence of the chromosomal gene for human fibroblast (beta 1) interferon and of the flanking regions. Gene. 1981 Aug;14(3):137–143. doi: 10.1016/0378-1119(81)90109-8. [DOI] [PubMed] [Google Scholar]
  8. Denhardt D. T. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. doi: 10.1016/0006-291x(66)90447-5. [DOI] [PubMed] [Google Scholar]
  9. Derynck R., Content J., DeClercq E., Volckaert G., Tavernier J., Devos R., Fiers W. Isolation and structure of a human fibroblast interferon gene. Nature. 1980 Jun 19;285(5766):542–547. doi: 10.1038/285542a0. [DOI] [PubMed] [Google Scholar]
  10. Enquist L., Sternberg N. In vitro packaging of lambda Dam vectors and their use in cloning DNA fragments. Methods Enzymol. 1979;68:281–298. doi: 10.1016/0076-6879(79)68020-5. [DOI] [PubMed] [Google Scholar]
  11. Epstein L. B. Interferon-gamma: success, structure and speculation. Nature. 1982 Feb 11;295(5849):453–454. doi: 10.1038/295453a0. [DOI] [PubMed] [Google Scholar]
  12. Gillespie D., Carter W. Concerted evolution of human interferon alpha genes. J Interferon Res. 1983;3(1):83–88. doi: 10.1089/jir.1983.3.83. [DOI] [PubMed] [Google Scholar]
  13. Goeddel D. V., Leung D. W., Dull T. J., Gross M., Lawn R. M., McCandliss R., Seeburg P. H., Ullrich A., Yelverton E., Gray P. W. The structure of eight distinct cloned human leukocyte interferon cDNAs. Nature. 1981 Mar 5;290(5801):20–26. doi: 10.1038/290020a0. [DOI] [PubMed] [Google Scholar]
  14. Goeddel D. V., Shepard H. M., Yelverton E., Leung D., Crea R., Sloma A., Pestka S. Synthesis of human fibroblast interferon by E. coli. Nucleic Acids Res. 1980 Sep 25;8(18):4057–4074. doi: 10.1093/nar/8.18.4057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Goeddel D. V., Yelverton E., Ullrich A., Heyneker H. L., Miozzari G., Holmes W., Seeburg P. H., Dull T., May L., Stebbing N. Human leukocyte interferon produced by E. coli is biologically active. Nature. 1980 Oct 2;287(5781):411–416. doi: 10.1038/287411a0. [DOI] [PubMed] [Google Scholar]
  16. Gray P. W., Goeddel D. V. Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859–863. doi: 10.1038/298859a0. [DOI] [PubMed] [Google Scholar]
  17. Gray P. W., Leung D. W., Pennica D., Yelverton E., Najarian R., Simonsen C. C., Derynck R., Sherwood P. J., Wallace D. M., Berger S. L. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503–508. doi: 10.1038/295503a0. [DOI] [PubMed] [Google Scholar]
  18. Havell E. A., Yamazaki S., Vilcek J. Altered molecular species of human interferon produced in the presence of inhibitors of glycosylation. J Biol Chem. 1977 Jun 25;252(12):4425–4427. [PubMed] [Google Scholar]
  19. Hiscott J., Cantell K., Weissmann C. Differential expression of human interferon genes. Nucleic Acids Res. 1984 May 11;12(9):3727–3746. doi: 10.1093/nar/12.9.3727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lawn R. M., Adelman J., Dull T. J., Gross M., Goeddel D., Ullrich A. DNA sequence of two closely linked human leukocyte interferon genes. Science. 1981 Jun 5;212(4499):1159–1162. doi: 10.1126/science.6165082. [DOI] [PubMed] [Google Scholar]
  21. Lawn R. M., Fritsch E. F., Parker R. C., Blake G., Maniatis T. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA. Cell. 1978 Dec;15(4):1157–1174. doi: 10.1016/0092-8674(78)90043-0. [DOI] [PubMed] [Google Scholar]
  22. Lawn R. M., Gross M., Houck C. M., Franke A. E., Gray P. V., Goeddel D. V. DNA sequence of a major human leukocyte interferon gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5435–5439. doi: 10.1073/pnas.78.9.5435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lund B., Edlund T., Lindenmaier W., Ny T., Collins J., Lundgren E., von Gabain A. Novel cluster of alpha-interferon gene sequences in a placental cosmid DNA library. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2435–2439. doi: 10.1073/pnas.81.8.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. McGrath J. P., Levinson A. D. Bacterial expression of an enzymatically active protein encoded by RSV src gene. Nature. 1982 Feb 4;295(5848):423–425. doi: 10.1038/295423a0. [DOI] [PubMed] [Google Scholar]
  27. Mellor A. L., Weiss E. H., Ramachandran K., Flavell R. A. A potential donor gene for the bm1 gene conversion event in the C57BL mouse. Nature. 1983 Dec 22;306(5945):792–795. doi: 10.1038/306792a0. [DOI] [PubMed] [Google Scholar]
  28. Messing J., Crea R., Seeburg P. H. A system for shotgun DNA sequencing. Nucleic Acids Res. 1981 Jan 24;9(2):309–321. doi: 10.1093/nar/9.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Miyata T., Hayashida H. Recent divergence from a common ancestor of human IFN-alpha genes. Nature. 1982 Jan 14;295(5845):165–168. doi: 10.1038/295165a0. [DOI] [PubMed] [Google Scholar]
  30. Mogensen K. E., Cantell K. Human leukocyte interferon: a role for disulphide bonds. J Gen Virol. 1974 Jan;22(1):95–103. doi: 10.1099/0022-1317-22-1-95. [DOI] [PubMed] [Google Scholar]
  31. Nagata S., Mantei N., Weissmann C. The structure of one of the eight or more distinct chromosomal genes for human interferon-alpha. Nature. 1980 Oct 2;287(5781):401–408. doi: 10.1038/287401a0. [DOI] [PubMed] [Google Scholar]
  32. Nagata S., Taira H., Hall A., Johnsrud L., Streuli M., Ecsödi J., Boll W., Cantell K., Weissmann C. Synthesis in E. coli of a polypeptide with human leukocyte interferon activity. Nature. 1980 Mar 27;284(5754):316–320. doi: 10.1038/284316a0. [DOI] [PubMed] [Google Scholar]
  33. Naylor S. L., Sakaguchi A. Y., Shows T. B., Law M. L., Goeddel D. V., Gray P. W. Human immune interferon gene is located on chromosome 12. J Exp Med. 1983 Mar 1;157(3):1020–1027. doi: 10.1084/jem.157.3.1020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ohno S., Taniguchi T. Structure of a chromosomal gene for human interferon beta. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5305–5309. doi: 10.1073/pnas.78.9.5305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Owerbach D., Rutter W. J., Shows T. B., Gray P., Goeddel D. V., Lawn R. M. Leukocyte and fibroblast interferon genes are located on human chromosome 9. Proc Natl Acad Sci U S A. 1981 May;78(5):3123–3127. doi: 10.1073/pnas.78.5.3123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Perler F., Efstratiadis A., Lomedico P., Gilbert W., Kolodner R., Dodgson J. The evolution of genes: the chicken preproinsulin gene. Cell. 1980 Jun;20(2):555–566. doi: 10.1016/0092-8674(80)90641-8. [DOI] [PubMed] [Google Scholar]
  38. Proudfoot N. J., Brownlee G. G. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. doi: 10.1038/263211a0. [DOI] [PubMed] [Google Scholar]
  39. Ragg H., Weissmann C. Not more than 117 base pairs of 5'-flanking sequence are required for inducible expression of a human IFN-alpha gene. Nature. 1983 Jun 2;303(5916):439–442. doi: 10.1038/303439a0. [DOI] [PubMed] [Google Scholar]
  40. Revel M. Genetic and functional diversity of interferons in man. Interferon. 1983;5:205–239. [PubMed] [Google Scholar]
  41. Rimm D. L., Horness D., Kucera J., Blattner F. R. Construction of coliphage lambda Charon vectors with BamHI cloning sites. Gene. 1980 Dec;12(3-4):301–309. doi: 10.1016/0378-1119(80)90113-4. [DOI] [PubMed] [Google Scholar]
  42. Romero-Herrera A. E., Lehmann H., Joysey K. A., Friday A. E. Molecular evolution of myoglobin and the fossil record: a phylogenetic synthesis. Nature. 1973 Dec 14;246(5433):389–395. doi: 10.1038/246389a0. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Schon E. A., Wernke S. M., Lingrel J. B. Gene conversion of two functional goat alpha-globin genes preserves only minimal flanking sequences. J Biol Chem. 1982 Jun 25;257(12):6825–6835. [PubMed] [Google Scholar]
  45. Sehgal P. B., Sagar A. D. Heterogeneity of poly(I) x poly(C)-induced human fibroblast interferon mRNA species. Nature. 1980 Nov 6;288(5786):95–97. doi: 10.1038/288095a0. [DOI] [PubMed] [Google Scholar]
  46. Shaw G. D., Boll W., Taira H., Mantei N., Lengyel P., Weissmann C. Structure and expression of cloned murine IFN-alpha genes. Nucleic Acids Res. 1983 Feb 11;11(3):555–573. doi: 10.1093/nar/11.3.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. 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]
  49. Streuli M., Hall A., Boll W., Stewart W. E., 2nd, Nagata S., Weissmann C. Target cell specificity of two species of human interferon-alpha produced in Escherichia coli and of hybrid molecules derived from them. Proc Natl Acad Sci U S A. 1981 May;78(5):2848–2852. doi: 10.1073/pnas.78.5.2848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Streuli M., Nagata S., Weissmann C. At least three human type alpha interferons: structure of alpha 2. Science. 1980 Sep 19;209(4463):1343–1347. doi: 10.1126/science.6158094. [DOI] [PubMed] [Google Scholar]
  51. Taniguchi T., Mantei N., Schwarzstein M., Nagata S., Muramatsu M., Weissmann C. Human leukocyte and fibroblast interferons are structurally related. Nature. 1980 Jun 19;285(5766):547–549. doi: 10.1038/285547a0. [DOI] [PubMed] [Google Scholar]
  52. Taylor J. M., Illmensee R., Summers J. Efficeint transcription of RNA into DNA by avian sarcoma virus polymerase. Biochim Biophys Acta. 1976 Sep 6;442(3):324–330. doi: 10.1016/0005-2787(76)90307-5. [DOI] [PubMed] [Google Scholar]
  53. Todokoro K., Kioussis D., Weissmann C. Two non-allelic human interferon alpha genes with identical coding regions. EMBO J. 1984 Aug;3(8):1809–1812. doi: 10.1002/j.1460-2075.1984.tb02050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Ullrich A., Gray A., Goeddel D. V., Dull T. J. Nucleotide sequence of a portion of human chromosome 9 containing a leukocyte interferon gene cluster. J Mol Biol. 1982 Apr 15;156(3):467–486. doi: 10.1016/0022-2836(82)90261-3. [DOI] [PubMed] [Google Scholar]
  55. Ullrich A., Shine J., Chirgwin J., Pictet R., Tischer E., Rutter W. J., Goodman H. M. Rat insulin genes: construction of plasmids containing the coding sequences. Science. 1977 Jun 17;196(4296):1313–1319. doi: 10.1126/science.325648. [DOI] [PubMed] [Google Scholar]
  56. Van Damme J., Billiau A. Large-scale production of human fibroblast interferon. Methods Enzymol. 1981;78(Pt A):101–119. doi: 10.1016/0076-6879(81)78103-5. [DOI] [PubMed] [Google Scholar]
  57. Weck P. K., Apperson S., Stebbing N., Gray P. W., Leung D., Shepard H. M., Goeddel D. V. Antiviral activities of hybrids of two major human leukocyte interferons. Nucleic Acids Res. 1981 Nov 25;9(22):6153–6166. doi: 10.1093/nar/9.22.6153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Weidle U., Weissmann C. The 5'-flanking region of a human IFN-alpha gene mediates viral induction of transcription. Nature. 1983 Jun 2;303(5916):442–446. doi: 10.1038/303442a0. [DOI] [PubMed] [Google Scholar]
  59. Weissenbach J., Chernajovsky Y., Zeevi M., Shulman L., Soreq H., Nir U., Wallach D., Perricaudet M., Tiollais P., Revel M. Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia coli cloning studies. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7152–7156. doi: 10.1073/pnas.77.12.7152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Weissmann C., Nagata S., Boll W., Fountoulakis M., Fujisawa A., Fujisawa J. I., Haynes J., Henco K., Mantei N., Ragg H. Structure and expression of human IFN-alpha genes. Philos Trans R Soc Lond B Biol Sci. 1982 Sep 24;299(1094):7–28. doi: 10.1098/rstb.1982.0102. [DOI] [PubMed] [Google Scholar]
  61. Wetzel R. Assignment of the disulphide bonds of leukocyte interferon. Nature. 1981 Feb 12;289(5798):606–607. doi: 10.1038/289606a0. [DOI] [PubMed] [Google Scholar]
  62. Wilson V., Jeffreys A. J., Barrie P. A., Boseley P. G., Slocombe P. M., Easton A., Burke D. C. A comparison of vertebrate interferon gene families detected by hybridization with human interferon DNA. J Mol Biol. 1983 Jun 5;166(4):457–475. doi: 10.1016/s0022-2836(83)80281-2. [DOI] [PubMed] [Google Scholar]
  63. Zoon K. C., Smith M. E., Bridgen P. J., Anfinsen C. B., Hunkapiller M. W., Hood L. E. Amino terminal sequence of the major component of human lymphoblastoid interferon. Science. 1980 Feb 1;207(4430):527–528. doi: 10.1126/science.7352260. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES