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The birth and development of the DNA theory of inheritance: sixty years since the discovery of the structure of DNA


The development of the DNA theory of inheritance culminated in the publication of the molecular structure of DNA 60 years ago. This paper describes this development, beginning with the discovery of DNA as a chemical substance by Friedrich Miescher in 1869, followed by its basic chemical analysis and demonstration of its participation in the structure of chromosomes. Subsequently it was discovered by Oswald Avery in 1944 that DNA was the genetic material, and then Erwin Chargaff showed that the proportions of the bases included in the structure of DNA followed a certain law. These findings, in association with the biophysical studies of Maurice Wilkins and Rosalind Franklin with Raymond Gosling, led James Watson and Francis Crick to the discovery of the double-helical structure of DNA in 1953. The paper ends with a short description of the development of the DNA theory of inheritance after the discovery of the double helix.

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  • Alloway J. L. 1932 The transformation in vitro of R pneumococci into S form of different specific types by the use of filtered pneumococcal extracts. J. Exp. Med. 55, 91–99.

  • Alloway J. L. 1933 Further observations on the use of pneumococcus extracts in affecting transformation of type in vitro. J. Exp. Med. 57, 265–278.

  • Altmann R. 1889 ber Nukleinsuren. Arch. f. Anatomie u. Physiol., Leipzig Physiol. Abt. 524–536.

  • Astbury W. T. and Bell F. O. 1938 X-ray study of thymonucleic acid. Nature 141, 747–748.

  • Avery O. T., MacLeod C. M. and MacCarty M. 1944 Studies on the chemical nature of the substance inducing transformation of Pneumococcal types. Induction of transformation by a deoxyribonucleic acid fraction isolated from Pneumococcus type III. J. Exp. Med. 79, 137–159.

  • Bartlett J. M. and Stirling D. 2003 A short history of the polymerase chain reaction. Methods Mol. Biol. 226, 3–6.

  • Beadle G. W. and Tatum E. L. 1941 Genetic control of biochemical reactions in Neurospora. Proc. Natl. Acad. Sci. USA 27, 499–506.

  • Boivin A., Vendrely R. and Vendrely C. 1948 L’acide dsoxyribonuclique du noyau cellulaire, dpositaire des caractres hrditaires: arguments d’ordre analytique. C. R. Hebd. Sanc. Acad. Sci., Paris 226, 1061–1063.

  • Boveri T. 1902 ber mehrpolige Mitosen als Mittel zur Analyse des Zellkerns. Verh. Phys.-Med. Ges. Vrzb. N.F. 35, 60–90.

  • Boveri T. 1903 ber die Konstitution der chromatischen Kernsubstanz. Verh. Deutsch. Zool. Ges. Wrzb. 13, 10–33.

  • Boveri T. H. 1904 Ergebnisse ber die Konstitution der chromatischen Substanz des Zellkerns. Gustav Fischer, Jena.

  • Brenner S., Jacob, F. and Meselson M. 1961 An unstable intermediate carrying information from genes to ribosomes for protein synthesis. Nature 190, 576–581.

  • Bresch C. and Hausmann R. 1972 Klassische und molekulare Genetik. Third expanded edition. Springer-Verlag, Berlin, Heidelberg, New York, USA.

  • Bridges C. B. 1914 Direct proof through non-disjunction that sex-linked genes of Drosophila are borne by the X-chromosome. Science 40, 107–109.

  • Bridges C. B. 1916 Non-disjunction as proof of the chromosome theory of heredity. Genetics 1, 1-52, 107–163.

  • Bridges C. B. 1935 Salivary chromosome maps with a key to the banding of the chromosomes of Drosophila Melanogaster. J. Hered. 26, 60–64.

  • Bridges C. B. 1938 A revised map of the salivary gland X-chromosome of Drosophila melanogaster. J. Hered. 29, 11–13.

  • Chargaff E. 1950 Chemical specificity of nucleic acids and mechanism of their enzymatic degradation. Experientia 6, 201–209.

  • Chargaff E. 1951 Structure and function of nucleic acid as cell constituent. Fed. Proc. 10, 654–659.

  • Chargaff E., Vischer E., Doniger R., Green C. and Misani F. 1949 The composition of the desoxypentose nucleic acid of thymus and spleen. J. Biol. Chem. 177, 405–416.

  • Creighton H. B. and McClintock B. 1931 A correlation of cytological and genetical crossing-over in Zea mays. Proc. Natl. Acad. Sci. USA 17, 492–497.

  • Crick F. 1970 Central dogma of molecular biology. Nature 227, 561–563.

  • Crick F. H. C. 1958 On protein synthesis. Symp. Soc. Exp. Biol. 12, 138–167.

  • Crick F. H. C., Barnett L., Brenner S. and Watts-Tobin R. J. 1961 General nature of the genetic code for proteins. Nature 192, 1227–1232.

  • Crick F. H. C., Wang J. C. and Bauer W. R. 1979 Is DNA really a double helix? J. Mol. Biol. 129, 449–461.

  • Dahm R. 2008 Discovering DNA: Friedrich Miescher and the early years of nucleic acid research. Hum. Genet. 122, 565–581

  • Dawson M. H. and Sia R. H. P. 1931 In vitro transformation of pneumococcal types. I. A technique for inducing transformation of pneumococcal types in vitro. J. Exp. Med. 54, 681–700.

  • Deichmann U. 2004 Early responses to Avery et al.’s paper on DNA as hereditary material. Hist. Stud. Phys. Biol. Sci. 34, 207–232.

  • Dobzhansky Th. 1929 Genetical and cytological proof of translocations involving the third and fourth chromosome in Drosophila melanogaster. Biol. Zentralbl. 49, 408–419.

  • Dounce A. L. 1952 Duplicating mechanism for peptide chain and nucleic acid synthesis. Enzymologia 15, 503–507.

  • Falk R. 2009 Genetic analysis: a history of genetic thinking. Cambridge University Press, Cambridge, UK.

  • Franklin R. E. and Gosling R. G. 1953 Molecular structure of nucleic acids. Molecular configuration in sodium thymonucleate. Nature 171, 740–741.

  • Gamow G. 1954 Possible relation between deoxyribonucleic acid and protein structures. Nature 173, 318.

  • Green R. E., Krause J., Ptak S. E., Briggs A. W., Ronan M. T., Simons J. F. et al. 2006 Analysis of one million base pairs of Neanderthal DNA. Nature 444, 330–336.

  • Griffith F. 1928 Significance of pneumococcal types. J. Hyg. 27, 113–159.

  • Griffiths A. J. F., Wessler S. R., Lewontin R. C. and Carroll S. B. 2008 Introduction to Genetic Analysis, 9th edition. W. H. Freeman, New York, USA.

  • Hershey A. D. and Chase M. 1952 Independent functions of viral protein and nucleic acid in growth of bacteriophage. J. Gen. Physiol. 36, 39–56.

  • Hollaender A. and Emmons C. W. 1941 Wavelength dependence of mutation production in ultraviolet with special emphasis on fungi. Cold Spring Harb. Symp. Quant. Biol. 9, 179–186.

  • Huberman J. A. and Riggs D. A. 1968 On the mechanism of DNA replication in mammalian chromosomes. J. Mol. Biol. 32, 327–341.

  • International Human Genome Sequencing Consortium 2001 Initial sequencing and analysis of the human genome. Nature 409, 860–921.

  • International Human Genome Sequencing Consortium 2004 Finishing the euchromatic sequence of the human genome. Nature 431, 931–945.

  • Jackson D., Symons R. and Berg P. 1972 Biochemical method for inserting new genetic information into DNA of simian virus 40: circular SV40 DNA molecules containing lambda phage genes and the galactose operon of Escherichia coli. Proc. Natl. Acad. Sci. USA 69, 2904–2909.

  • Jacob F. and Monod J. 1961 Genetic regulatory mechanisms in the synthesis of proteins. J. Mol. Biol. 3, 318–356.

  • Janning W. and Knust E. 2004 Genetik: allgemeine genetik, molekulare genetik, entwicklungsgenetik. Georg Thieme Verlag, Stuttgart, New York.

  • Judson H. F. 1996 The eighth day of creation. Markers of the revolution in biology. Expanded edition. Cold Spring Harbor Laboratory Press, New York.

  • Knapp E. and Schreiber H. 1939 Quantitative analyse der mutationsauslsende wirkung monochromatischen UV-lichtes in spermatozoiden von Sphaerocarpus. In Proceedings of the7th International Congress of Genetics, Edinburgh (ed. R. C. Punnett), pp. 175-176. Cambridge University Press, Cambridge.

  • Kossel A. 1913 Beziehungen der Chemie zur Physiologie. In Die Kultur der Gegenwart, ihre Entwicklung und ihre Ziele: Chemie (ed. Ev. Meyer), pp. 376-412. Teubner, Leipzig.

  • Kossel A. and Neumann A. 1893 ber das thymin, ein spaltungsprodukt der nukleinsure. Ber. deutsch. chem. Ges. 26, 2753–2756.

  • Maxam A. M. and Gilbert W. 1977 A new method for sequencing DNA. Proc. Natl. Acad. Sci. USA 74, 560–564.

  • McClung C. E. 1902 The accessory chromosome-sex determinant? Biol. Bull. (Woods Hole) 3, 43–84.

  • Mendel G. 1866 Versuche ber Pflanzenhybriden. Verh. naturf. Ver. Brnn 4, 3–47.

  • Meselson M. and Stahl F. W. 1958a The replication of DNA. Cold Spring Harb. Symp. Quant.Biol. 23, 9–12.

  • Meselson M. and Stahl F. W. 1958b The replication of DNA in Escherichia coli. Proc. Natl. Acad. Sci. USA 44, 671–682.

  • Miescher F. 1871 Über die chemische zusammensetzung der eiterzellen. Hoppe-Seyler’s Med.-chem. Unters. 4, 441–460.

  • Miescher F. 1874a Das protamin, eine neue organische basis aus den samenfden des rheinlachses. Ber. deutsch. chem. Ges. 7, 376–379.

  • Miescher F. 1874b Die spermatozoen einiger wilbertiere. Ein Beitrag zur histochemie. Verh. naturf. Ges. Basel 6, 138–208.

  • Mirsky A. E. 1968 The discovery of DNA. Sci. Am. 218, 78–88.

  • Morgan T. H. 1910 Sex limited inheritance in Drosophila. Science 32, 120–122.

  • Morgan T. H. 1911 The application of the conception of pure lines to sex-limited inheritance and to sexual dimorphism.Am. Nat. 45, 65–78.

  • Morgan T. H. 1919 The physical basis of heredity. Yale University Press, New Haven, USA.

  • Morgan T. H. 1926 The theory of the gene. Yale University Press, New Haven, USA.

  • Morgan T. H., Sturtevant A. H., Muller H. J. and Bridges C. B. 1915 The mechanism of mendelian heredity. Henry Holt, New York, USA.

  • Muller H. J. and Painter T. S. 1929 The cytological expression of changes in gene alignment produced by X-rays in Drosophila. Am. Nat. 63, 193–200.

  • Noonan J. P., Coop G., Kudaravelli S., Smith D., Krause J., Alessi J. et al. 2006. Sequencing and analysis of Neanderthal genomic DNA. Science 314, 1113–1118.

  • Olby R. C. 1994 The path to the double helix the discovery of DNA. Dover Publications, New York, USA.

  • Painter T. S. 1933 A new method for the study of chromosome rearrangements and the plotting of chromosome maps. Science 78, 585–586.

  • Painter T. S. 1934 A new method for the study of chromosome aberrations and the plotting of chromosome maps in Drosophila melanogaster. Genetics 19, 175-188.

  • Pardee A. B., Jacob F. and Monod J. 1959 The genetic control and cytoplasmic expression of inducibility in the synthesis of ?-galactosidase by E. coli. J. Mol. Biol. 1, 165-178.

  • Portin P. 1993 The concept of the gene: Short history and present status. Q. Rev. Biol. 68, 173-223.

  • Portin P. 2007 Evolution of man in the light of molecular genetics: A review. Part I. Our evolutionary history and genomics. Hereditas 144, 80-95.

  • Portin P. 2009 The elusive concept of the gene. Hereditas 146, 112-117.

  • Portugal F. H. and Cohen J. S. 1977 A century of DNA: a history of the discovery of the structure and function of the genetic substance. MIT Press, Cambridge, UK.

  • Pääbo S. 2003 The mosaic that is our genome. Nature 421, 409-412.

  • Reich D., Green R. E., Kircher M., Krause J., Petterson N., Durand E. Y. et al. 2010 Genetic history of an archaic hominin group from Denisova Cave in Siberia. Nature 468, 1053-1060.

  • Rheinberger H.-J. 1998 Kurze Gesichte der Molekularbiologie. In Gesichte der biologie. Theorien, methoden, institutionen, kurzbiographien, 3., neubearbeitete und erweiterte Auflage (ed. I. Jahn), pp. 642-663. Gustav Fisher, Jena, Germany.

  • Riley M., Pardee A. B., Jacob F. and Monod J. 1960 On the expression of a structural gene. J. Mol. Biol. 2, 216–225.

  • Sanger F., Nicklen S. and Coulson A. R. 1977 DNA sequencing with chain-termination inhibitors. Proc. Natl. Acad. Sci. USA 74, 5463–5467.

  • Scally A., Dutheil J. Y., Hillier L. W., Jordan G. G., Goodhead I, Herrero J. et al. 2012 Insights into hominid evolution from the gorilla genome sequence. Nature 483, 169–175.

  • Southern E. M. 1975 Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98, 503-517.

  • Srb A. M. and Horowitz N. H. 1944 The ornithine cycle in Neurospora and its genetic control. J. Biol. Chem. 154, 129–139

  • Stadler L. J. and Uber F. M. 1942 Genetic effects of ultraviolet radiation in maize. IV Comparison of monochromatic radiation. Genetics 27, 84-118.

  • Stern C. 1931 Zytologisch-genetische Untersuchungen als Beweise für die Morgansche Theorie des Faktorenaustauschs. Biol. Zentralbl. 51, 547-587.

  • Sturtevant A. H. 1913 The linear arrangement of the six sex-linked factors in Drosophila, as shown by their mode of association. J. Exp. Zool. 14, 43-59.

  • Sutton W. S. 1903 The chromosomes in heredity. Biol. Bull. (Woods Hole) 4, 231-251.

  • Sutton W. S. 1903 The chromosomes in heredity. Biol. Bull. (Woods Hole) 4, 231-251. Taylor J. H., Woods P. S. and Hughes W. L. 1957 The organization and duplication of chromosomes as revealed by autoradiographic studies using tritium-labeled thymidine. Proc. Natl. Acad. Sci. USA 43, 122-128.

  • The Chimpanzee Sequencing and Analysis Consortium 2005 Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437, 69-87.

  • The ENCODE Project Consortium 2007 Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799-816.

  • The ENCODE Project Consortium 2012 An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74.

  • Vendrely R. and Vendrely C. 1948 La teneur du noyau cellulaire en acide dsoxyribonuclique a travers les organes les individus et les espces animales. Experientia 4, 434-436.

  • Venter J. C. and 275 other authors 2001 The sequence of the human genome. Science 291, 1304-1351.

  • Watson J. D. 1968 The double helix: a personal account of the discovery of the structure of DNA. Atheneum, New York, USA.

  • Watson J. D. and Crick F. H. C. 1953a Molecular structure of nucleic acids. A structure for deoxyribose nucleic acid. Nature 171, 737-738.

  • Watson J. D. and Crick F. H. C. 1953b Genetical implications of the structure of deoxyribonucleic acid. Nature 171, 964-967.

  • Watson J. D. and Crick F. H. C. 1954 The structure of DNA. Cold Spring Harb. Symp. Quant. Biol. 18, 123-131.

  • Whitehouse H. L. K. 1973 Towards an understanding of the mechanism of heredity, 3rd edition. Edward Arnold, London, UK.

  • Wilkins M. H. F., Stokes A. R. and Wilson H. R. 1953 Molecular structure of nucleic acids. Molecular structure of deoxypentose nucleic acids.Nature 171, 738-740.

  • Wilson E. B. 1905 The chromosomes in relation to the determination of sex in insects. Science 22, 500-502.

  • Wittmann H. G. and Wittmann-Liebold B. 1966 Protein chemical studies of two RNA viruses and their mutants. Cold Spring Harb. Symp. Quant. Biol. 31, 163-172.

  • Yanofsky C. 1963 Amino acid replacements associated with mutation and recombination in the A gene and their relationship to in vitro coding data. Cold Spring Harb. Symp. Quant. Biol. 28, 581-588.

  • Yanofsky C., Ito J. and Horn V. 1966 Amino acid replacements and the genetic code. Cold Spring Harb. Symp. Quant. Biol. 31, 151-162.

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My friend, Professor Harri Savilahti, Department of Biology, University of Turku, read the first version of the manuscript and made several suggestions for improvement, for which I express my sincere thanks. Special thanks to Maaria Tringham, M.Sc. and Damon Tringham, M.Phil., for checking the language.

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Correspondence to PETTER PORTIN.

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[Portin P. 2014 The birth and development of the DNA theory of inheritance: sixty years since the discovery of the structure of DNA. J. Genet. 93, xx–xx]

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PORTIN, P. The birth and development of the DNA theory of inheritance: sixty years since the discovery of the structure of DNA. J Genet 93, 293–302 (2014).

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