Skip to main content
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
. 1985 Oct;82(19):6455–6459. doi: 10.1073/pnas.82.19.6455

Conserved features of eukaryotic hsp70 genes revealed by comparison with the nucleotide sequence of human hsp70.

C Hunt, R I Morimoto
PMCID: PMC390735  PMID: 3931075

Abstract

We have determined the nucleotide sequence of the human hsp70 gene and 5' flanking region. The hsp70 gene is transcribed as an uninterrupted primary transcript of 2440 nucleotides composed of a 5' noncoding leader sequence of 212 nucleotides, a 3' noncoding region of 242 nucleotides, and a continuous open reading frame of 1986 nucleotides that encodes a protein with predicted molecular mass of 69,800 daltons. Upstream of the 5' terminus are the canonical TATAAA box, the sequence ATTGG that corresponds in the inverted orientation to the CCAAT motif, and the dyad sequence CTGGAAT/ATTCCCG that shares homology in 12 of 14 positions with the consensus transcription regulatory sequence common to Drosophila heat shock genes. Comparison of the predicted amino acid sequences of human hsp70 with the published sequences of Drosophila hsp70 and Escherichia coli dnaK reveals that human hsp70 is 73% identical to Drosophila hsp70 and 47% identical to E. coli dnaK. Surprisingly, the nucleotide sequences of the human and Drosophila genes are 72% identical and human and E. coli genes are 50% identical, which is more highly conserved than necessary given the degeneracy of the genetic code. The lack of accumulated silent nucleotide substitutions leads us to propose that there may be additional information in the nucleotide sequence of the hsp70 gene or the corresponding mRNA that precludes the maximum divergence allowed in the silent codon positions.

Full text

PDF
6459

Selected References

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

  1. Alitalo K., Ramsay G., Bishop J. M., Pfeifer S. O., Colby W. W., Levinson A. D. Identification of nuclear proteins encoded by viral and cellular myc oncogenes. Nature. 1983 Nov 17;306(5940):274–277. doi: 10.1038/306274a0. [DOI] [PubMed] [Google Scholar]
  2. Ashburner M., Bonner J. J. The induction of gene activity in drosophilia by heat shock. Cell. 1979 Jun;17(2):241–254. doi: 10.1016/0092-8674(79)90150-8. [DOI] [PubMed] [Google Scholar]
  3. Bardwell J. C., Craig E. A. Major heat shock gene of Drosophila and the Escherichia coli heat-inducible dnaK gene are homologous. Proc Natl Acad Sci U S A. 1984 Feb;81(3):848–852. doi: 10.1073/pnas.81.3.848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bienz M. Xenopus hsp 70 genes are constitutively expressed in injected oocytes. EMBO J. 1984 Nov;3(11):2477–2483. doi: 10.1002/j.1460-2075.1984.tb02159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Corces V., Pellicer A., Axel R., Meselson M. Integration, transcription, and control of a Drosophila heat shock gene in mouse cells. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7038–7042. doi: 10.1073/pnas.78.11.7038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cowie A., Kamen R. Multiple binding sites for polyomavirus large T antigen within regulatory sequences of polyomavirus DNA. J Virol. 1984 Dec;52(3):750–760. doi: 10.1128/jvi.52.3.750-760.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DeLucia A. L., Lewton B. A., Tjian R., Tegtmeyer P. Topography of simian virus 40 A protein-DNA complexes: arrangement of pentanucleotide interaction sites at the origin of replication. J Virol. 1983 Apr;46(1):143–150. doi: 10.1128/jvi.46.1.143-150.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dickerson R. E. The structures of cytochrome c and the rates of molecular evolution. J Mol Evol. 1971;1(1):26–45. doi: 10.1007/BF01659392. [DOI] [PubMed] [Google Scholar]
  10. Feldman L. T., Nevins J. R. Localization of the adenovirus E1Aa protein, a positive-acting transcriptional factor, in infected cells infected cells. Mol Cell Biol. 1983 May;3(5):829–838. doi: 10.1128/mcb.3.5.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fitch W. M. The molecular evolution of cytochrome c in eukaryotes. J Mol Evol. 1976 Jun 23;8(1):13–40. doi: 10.1007/BF01738880. [DOI] [PubMed] [Google Scholar]
  12. Hann S. R., Abrams H. D., Rohrschneider L. R., Eisenman R. N. Proteins encoded by v-myc and c-myc oncogenes: identification and localization in acute leukemia virus transformants and bursal lymphoma cell lines. Cell. 1983 Oct;34(3):789–798. doi: 10.1016/0092-8674(83)90535-4. [DOI] [PubMed] [Google Scholar]
  13. Hentschel C. C., Birnstiel M. L. The organization and expression of histone gene families. Cell. 1981 Aug;25(2):301–313. doi: 10.1016/0092-8674(81)90048-9. [DOI] [PubMed] [Google Scholar]
  14. Holmgren R., Corces V., Morimoto R., Blackman R., Meselson M. Sequence homologies in the 5' regions of four Drosophila heat-shock genes. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3775–3778. doi: 10.1073/pnas.78.6.3775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Holmgren R., Livak K., Morimoto R., Freund R., Meselson M. Studies of cloned sequences from four Drosophila heat shock loci. Cell. 1979 Dec;18(4):1359–1370. doi: 10.1016/0092-8674(79)90246-0. [DOI] [PubMed] [Google Scholar]
  16. Ingolia T. D., Craig E. A. Drosophila gene related to the major heat shock-induced gene is transcribed at normal temperatures and not induced by heat shock. Proc Natl Acad Sci U S A. 1982 Jan;79(2):525–529. doi: 10.1073/pnas.79.2.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ingolia T. D., Craig E. A., McCarthy B. J. Sequence of three copies of the gene for the major Drosophila heat shock induced protein and their flanking regions. Cell. 1980 Oct;21(3):669–679. doi: 10.1016/0092-8674(80)90430-4. [DOI] [PubMed] [Google Scholar]
  18. Ingolia T. D., Slater M. R., Craig E. A. Saccharomyces cerevisiae contains a complex multigene family related to the major heat shock-inducible gene of Drosophila. Mol Cell Biol. 1982 Nov;2(11):1388–1398. doi: 10.1128/mcb.2.11.1388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Jones K. A., Tjian R. Essential contact residues within SV40 large T antigen binding sites I and II identified by alkylation-interference. Cell. 1984 Jan;36(1):155–162. doi: 10.1016/0092-8674(84)90084-9. [DOI] [PubMed] [Google Scholar]
  20. Kalderon D., Richardson W. D., Markham A. F., Smith A. E. Sequence requirements for nuclear location of simian virus 40 large-T antigen. Nature. 1984 Sep 6;311(5981):33–38. doi: 10.1038/311033a0. [DOI] [PubMed] [Google Scholar]
  21. Kingston R. E., Baldwin A. S., Jr, Sharp P. A. Regulation of heat shock protein 70 gene expression by c-myc. Nature. 1984 Nov 15;312(5991):280–282. doi: 10.1038/312280a0. [DOI] [PubMed] [Google Scholar]
  22. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Lemischka I. R., Farmer S., Racaniello V. R., Sharp P. A. Nucleotide sequence and evolution of a mammalian alpha-tubulin messenger RNA. J Mol Biol. 1981 Sep 5;151(1):101–120. doi: 10.1016/0022-2836(81)90223-0. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Nevins J. R. Induction of the synthesis of a 70,000 dalton mammalian heat shock protein by the adenovirus E1A gene product. Cell. 1982 Jul;29(3):913–919. doi: 10.1016/0092-8674(82)90453-6. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Proudfoot N. The end of the message. Nature. 1982 Aug 5;298(5874):516–517. doi: 10.1038/298516a0. [DOI] [PubMed] [Google Scholar]
  29. Ruley H. E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983 Aug 18;304(5927):602–606. doi: 10.1038/304602a0. [DOI] [PubMed] [Google Scholar]
  30. Saito H., Uchida H. Initiation of the DNA replication of bacteriophage lambda in Escherichia coli K12. J Mol Biol. 1977 Jun 15;113(1):1–25. doi: 10.1016/0022-2836(77)90038-9. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Schöffl F., Raschke E., Nagao R. T. The DNA sequence analysis of soybean heat-shock genes and identification of possible regulatory promoter elements. EMBO J. 1984 Nov;3(11):2491–2497. doi: 10.1002/j.1460-2075.1984.tb02161.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wright P. J., DeLucia A. L., Tegtmeyer P. Sequence-specific binding of simian virus 40 A protein to nonorigin and cellular DNA. Mol Cell Biol. 1984 Dec;4(12):2631–2638. doi: 10.1128/mcb.4.12.2631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wu B. J., Morimoto R. I. Transcription of the human hsp70 gene is induced by serum stimulation. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6070–6074. doi: 10.1073/pnas.82.18.6070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wu B., Hunt C., Morimoto R. Structure and expression of the human gene encoding major heat shock protein HSP70. Mol Cell Biol. 1985 Feb;5(2):330–341. doi: 10.1128/mcb.5.2.330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zylicz M., Georgopoulos C. Purification and properties of the Escherichia coli dnaK replication protein. J Biol Chem. 1984 Jul 25;259(14):8820–8825. [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