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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
. 1983 Jun;80(12):3716–3720. doi: 10.1073/pnas.80.12.3716

Isolation and characterization of human myosin heavy chain genes.

L A Leinwand, L Saez, E McNally, B Nadal-Ginard
PMCID: PMC394121  PMID: 6304733

Abstract

We have isolated four unique human sarcomeric myosin heavy chain (MHC) genomic clones using rat MHC cDNA clones as probes. Three of these clones contain adult skeletal muscle-specific DNA sequences, whereas one clone contains embryonic skeletal muscle-specific sequences. This developmental and tissue specificity was determined by hybridization of each of the human clones to MHC mRNA from different muscle tissues. Cross-hybridization studies indicate that certain sequences of the human MHC genes have been conserved through evolution while other portions have diverged considerably. Preliminary evidence demonstrates that the MHC gene family is polymorphic in human populations. Each of the human MHC genes was shown to have repetitive sequences in multiple positions, both within the gene and in adjacent flanking DNA sequences. We have shown that, in contrast, four rat MHC genes have far fewer repetitive sequences even though two of the four genes contain the same muscle specificity as the human genes. Therefore, these genes may be useful to study gene evolution and repetitive sequence transposition.

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Selected References

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  1. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [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. 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]
  4. Dalla-Favera R., Gelmann E. P., Gallo R. C., Wong-Staal F. A human onc gene homologous to the transforming gene (v-sis) of simian sarcoma virus. Nature. 1981 Jul 2;292(5818):31–35. doi: 10.1038/292031a0. [DOI] [PubMed] [Google Scholar]
  5. Davidson E. H., Britten R. J. Regulation of gene expression: possible role of repetitive sequences. Science. 1979 Jun 8;204(4397):1052–1059. doi: 10.1126/science.451548. [DOI] [PubMed] [Google Scholar]
  6. Derman E., Krauter K., Walling L., Weinberger C., Ray M., Darnell J. E., Jr Transcriptional control in the production of liver-specific mRNAs. Cell. 1981 Mar;23(3):731–739. doi: 10.1016/0092-8674(81)90436-0. [DOI] [PubMed] [Google Scholar]
  7. Haynes S. R., Toomey T. P., Leinwand L., Jelinek W. R. The Chinese hamster Alu-equivalent sequence: a conserved highly repetitious, interspersed deoxyribonucleic acid sequence in mammals has a structure suggestive of a transposable element. Mol Cell Biol. 1981 Jul;1(7):573–583. doi: 10.1128/mcb.1.7.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Houck C. M., Rinehart F. P., Schmid C. W. A ubiquitous family of repeated DNA sequences in the human genome. J Mol Biol. 1979 Aug 15;132(3):289–306. doi: 10.1016/0022-2836(79)90261-4. [DOI] [PubMed] [Google Scholar]
  9. Leinwand L. A., Wydro R. M., Nadal-Ginard B. Small RNA molecules related to the Alu family of repetitive DNA sequences. Mol Cell Biol. 1982 Nov;2(11):1320–1330. doi: 10.1128/mcb.2.11.1320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mahdavi V., Periasamy M., Nadal-Ginard B. Molecular characterization of two myosin heavy chain genes expressed in the adult heart. Nature. 1982 Jun 24;297(5868):659–664. doi: 10.1038/297659a0. [DOI] [PubMed] [Google Scholar]
  11. Medford R. M., Wydro R. M., Nguyen H. T., Nadal-Ginard B. Cytoplasmic processing of myosin heavy chain messenger RNA: evidence provided by using a recombinant DNA plasmid. Proc Natl Acad Sci U S A. 1980 Oct;77(10):5749–5753. doi: 10.1073/pnas.77.10.5749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nguyen H. T., Gubits R. M., Wydro R. M., Nadal-Ginard B. Sarcomeric myosin heavy chain is coded by a highly conserved multigene family. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5230–5234. doi: 10.1073/pnas.79.17.5230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Page G. S., Smith S., Goodman H. M. DNA sequence of the rat growth hormone gene: location of the 5' terminus of the growth hormone mRNA and identification of an internal transposon-like element. Nucleic Acids Res. 1981 May 11;9(9):2087–2104. doi: 10.1093/nar/9.9.2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pearson W. R., Wu J. R., Bonner J. Analysis of rat repetitive DNA sequences. Biochemistry. 1978 Jan 10;17(1):51–59. doi: 10.1021/bi00594a008. [DOI] [PubMed] [Google Scholar]
  15. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  16. Shen C. K., Maniatis T. The organization of repetitive sequences in a cluster of rabbit beta-like globin genes. Cell. 1980 Feb;19(2):379–391. doi: 10.1016/0092-8674(80)90512-7. [DOI] [PubMed] [Google Scholar]
  17. Sinha A. M., Umeda P. K., Kavinsky C. J., Rajamanickam C., Hsu H. J., Jakovcic S., Rabinowitz M. Molecular cloning of mRNA sequences for cardiac alpha- and beta-form myosin heavy chains: expression in ventricles of normal, hypothyroid, and thyrotoxic rabbits. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5847–5851. doi: 10.1073/pnas.79.19.5847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Whalen R. G., Schwartz K., Bouveret P., Sell S. M., Gros F. Contractile protein isozymes in muscle development: identification of an embryonic form of myosin heavy chain. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5197–5201. doi: 10.1073/pnas.76.10.5197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wydro R. M., Nguyen H. T., Gubits R. M., Nadal-Ginard B. Characterization of sarcomeric myosin heavy chain genes. J Biol Chem. 1983 Jan 10;258(1):670–678. [PubMed] [Google Scholar]
  21. 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]

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