165 DNA | Summary

DNA

DNA, or deoxyribonucleic acid, is vital to all living organisms. The discovery of its structure and function underpins many of the recent advances that have been made in understanding the molecular cause of disease and the formulation of new avenues of treatment.

This vial contains some of the first DNA Friedrich Miescher isolated from salmon sperm. It is in the possession of the University of Turbingen, Germany. Credit: Alfons Renz.

Definition

DNA is a complex, long-chained molecule that contains the genetic blueprint for building and maintaining all living organisms. Found in nearly all cells, DNA carries the instructions needed to create proteins, specific molecules essential to the development and functioning of the body. It also transfers hereditary information between generations.

Importance

DNA is central to biotechnology and medicine by virtue of the fact that it not only provides the basic blueprint for all life, it is a fundamental determinant of how the body functions and the disease process. Understanding the structure and function of DNA has helped revolutionise the investigation of disease pathways, assess an individual’s genetic susceptibility to specific diseases, diagnose genetic disorders, and formulate new drugs. It is also critical to the identification of pathogens.

Aside from its medical uses, the fact that DNA is unique to each individual makes it a vital forensic tool identifying criminals, the remains of a missing person, and determining the biological parent of a child. Within agriculture DNA is also used to help improve animal livestock and plants.

Discovery

The discovery of DNA stretches back to 1869, when Friedrich Miescher, a Swiss physician and biologist, began examining leucocytes, a type of white blood cell, he had sourced from pus collected on fresh surgical bandages. This he did while working in the laboratory of Felix Hoppe-Seyler in Tubingen, Germany as part of project to determine the chemical building blocks of cells. On looking through the microscope he observed that a substance separated from the solution of the cells whenever he added an acid and then dissolved again once alkali was added. The compound bore no resemblance to any known protein. Believing the substance to originate from the nuceli of the cell, Miescher nicknamed it 'nuclein'. On investigating further he discovered nuclein to be present in many other tissues. While possessing only simple tools and methods, by 1874 Miescher had come close to working out the genetic role of nuclein. He lacked sufficient communication skills, however, to convey the importance of what he had found to the wider scientific world.

In 1881 Albrecht Kossel, a German biochemist, renamed Miescher's compound deoxyribonucleic acid (DNA) based on the fact that he had discovered it to be a nucleic acid. Following this, he began working out its chemical composition. By 1901 he determined it to be made up of five nitrogen bases: adenine (A), cytosine (C), guanine (G), thymine (T) and uracil (U).

For many decades DNA remained little studied because it was assumed to be an inert substance incapable of carrying genetic material because of its simple structure. Proteins were instead thought to be the carriers of genetic material. In part this was because they had a more complex structure, being made up of 20 different amino acids.

It would not be until the mid 20th century that attitudes towards DNA began to change. This was prompted by the work of Oswald Avery at Rockefeller Institute in New York. From the early 1930s, Avery began to investigate how a type of non-infectious bacteria associated with pneumonia could transform into dangerous virulent forms if mixed with dead cells from the virulent strain and carried this trait into their offspring. The phenomenon had been first observed by Fred Griffith, a British physician, in 1928. By 1944 Avery had demonstrated with the help of his colleagues Colin MacLeod and Maclyn McCarty, that the transformation of the bacteria was linked to a stringy white substance – DNA. While not universally accepted at the time, Avery's finding helped kindle a new interest in DNA. It would take another few years before scientists finally accepted that it was DNA, not proteins, that carried DNA. It was finally agreed following experiments conducted by Alfred Hershey and Martha Hershey at Cold Spring Harbor in 1952.

By the 1950s a number of researchers had begun to investigate the structure of DNA in the hope that this would reveal how the molecule worked. Its structure was finally unveiled in 1953 through the combined efforts of the biophysicists Rosalind Franklin and Maurice Wilkins, based at King's College London, and Francis Crick and James Watson based in the Cavendish Laboratory, Cambridge University. Their work determined DNA to be a long linear molecule made up of two strands coiled around each other in a spiral configuration later known as the 'double helix'. Each strand was made up of four complementary nucleotides, chemical subunits: adenine (A), cytosine (C), guanine (G) and thymine (T). The two strands were oriented in opposite directions so that adenine always joined thymines (A T) and cytosines were linked with guanines (C G). Watson and Crick argued this structure helped each strand to reconstruct the other and facilitate the passing on of hereditary information.

Application

The analysis of DNA is pivotal to understanding both the biological mechanisms of life and diseases that arise when this process goes wrong. Many different applications have been developed to understand this process. Today scientists can analyse the molecule through a range of techniques, including DNA sequencing which helps work out its structure, through to PCR, which rapidly amplifies tiny quantities of DNA into billions of copies. Such techniques underpin all tests carried out today to for example identify a genetic mutation that causes cancer, or to determine whether a person carries a gene for a hereditary disease that can be passed on to their offspring. In addition, scientists have found ways to manipulate and construct new forms of DNA, known as recombinant DNA or gene cloning. Such technology is crucial to the mass production of many drugs, such as interferon, and the development of gene therapy.

DNA: timeline of key events

Date Event People Places
1842First observation of chromosomes by Swiss botanist Karl von NageliNageli
1864 - 1865Nucleus shown to contain genetic substanceHertwig, von Kolliker, Strasburger, Weismann University of Munich, University of Wurzburg, University of Freiburg
1869Discovery of DNAMiescher University of Tubingen
February 25, 1869Phoebus Levene was bornLevene
1871Papers describe DNA for first timeMiescher, Hoppe-Seyler, PloszUniversity of Tubingen
1872Walther Flemming, German biologist, describes chromosomes and examines their behaviour during cell division. FlemmingUniversity of Kiel
1877 - 1880Nucleic acid shown to have protein and non-protein componentsKosselUniversity of Tubingen
October 21, 1877 Oswald Theodore Avery was born in Halifax, CanadaAveryRockefeller University
1885 - 1901Nucleic acids structure determinedKosselInstitute of Physiology, University of Berlin, University of Marburg
1889Richard Altmann, German pathologist, renames nuclein as nucleic acidAltmannLeipzig University
August 26, 1895Johann Friedrich Miescher diedMiescher
1902Chromosomes linked with inheritanceBoveri, GarrodZoological-Zootomical Institute, Columbia University
1903The notion genetics is introducedJohannsenRoyal Veterinary University
September 24, 1905Severo Ochoa was born in Luarca, SpainOchoaNew York University
September 24, 1905Severo Ochoa was born in Luarca, SpainOchoaNew York University
October 2, 1907Alexander R Todd was born in Glasgow, ScotlandToddUniversity of Manchester
1909The term gene is first usedJohannsenUniversity of Copenhagen
1910First description of the building blocks of DNALeveneRockefeller University
1913First mapping of a chromosomeSturtevantColumbia University
December 14, 1914Solomon Spiegelman was born in Brooklyn, NY, USASpiegelmanUniversity of Minnesota
June 8, 1916Francis H C Crick was born in Northampton, United KingdomCrickLaboratory of Molecular Biology
December 15, 1916Maurice H F Wilkins was born in Pongaroa, New ZealandWilkinsKing's College London
March 3, 1918Arthur Kornberg was born in Brooklyn NY, USAKornbergStanford University
July 25, 1920Rosalind E Franklin was born in London, United KingdomFranklinKings College London
June 30, 1926Paul Berg was born in New York NY, USABergStanford University
1928Bacteria shown capable of transformationGriffithPathological Laboratory of the Ministry of Health
April 6, 1928James D Watson was born in Chicago IL, USAWatsonLaboratory of Molecular Biology
1929DNA nucleobases identifiedLeveneRockefeller University
June 3, 1929Werner Arber was born in Granichen, SwitzerlandArberUniversity of Geneva
April 26, 1932Michael Smith was born in Blackpool, United KingdomSmithUniversity of British Columbia
June 30, 1935Stanley Norman Cohen was born in Perth Amboy, NJ, USACohenStanford University
September 6, 1940Phoebus Levene diedLevene
1941Term 'genetic engineering' first coinedJost
September 6, 1943Richard J Roberts was bornRoberts
February 1, 1944DNA identified as a heritary agentAveryRockefeller University
December 1944Kary Banks Mullis was bornCetus Corporation
1949DNA content of a cells linked to a cell's number of chromosomesVendrely, BoivinPasteur Institute, Strasbourg School of Medicine
1949 - 1950DNA four base ratio shown to be always consistentCargraffColumbia University
September 1949Sickle cell shown to be caused by genetic mutationPaulingCalifornia Institute of Technology
November 1951Purified DNA and DNA in cells shown to have helical structureWilkinsKings College London
1952Bacteriophage experiments show DNA and not proteins to be genetic materialHershey, ChaseCarnegie Institution for Science
1952First observation of the modification of viruses by bacteriaLuria, HumanUniversity of Illinois
January 1952X-ray diffraction image, produced by Rosalind Franklin, shows DNA to have regularly repeating helical structureFranklinKings College London
April 1953DNA double-helix structure announcedCrick, WatsonCavendish Laboratory
April 1953Franklin's x-ray image of DNA publishedFranklinKings College London
1955Sanger completes the full sequence of amino acids in insulinSangerCambridge University
February 2, 1955Oswald Theodore Avery diedAveryRockefeller University
December 1955First discovery of the enzyme DNA polymeraseKornberg, Bessman, Simms, LehmanWashington University in St. Louis
1956DNA polymerase discovered to replicate DNAKornberg Washington University in St. Louis
1957Victor Ingram breaks the genetic code behind sickle-cell anaemia using Sanger's sequencing techniqueIngram, SangerCambridge University
1957First observation of messenger RNAAstrachan, VolkinOak Ridge National Laboratory
September 1957RNA proposed intermediary between DNA and proteinsCrickCavendish Laboratory
October 1957First synthesis of DNA in a test tubeKornbergWashington University in St. Louis
1958DNA replication explainedMeselson, StahlCalifornia Institute of Technology
1958Sanger awarded his first Nobel Prize in ChemistrySangerCambridge University
April 16, 1958Rosalind E Franklin diedFranklinKings College London
1960National Biomedical Research Foundation establishedLedleyGeorgetown University
1960Sanger begins to devise ways to sequence nucleic acids, starting with RNASangerCambridge University
1961 - 1966Genetic code cracked for the first timeKhorana, HolleyUniversity of Wisconsin, Cornell University
March 31, 1961Experiments reveal a type of RNA (messenger RNA) transports genetic information from the nucleus to the protein-making machinery in a cellBrenner, Crick, Jacob
May 1961Coding mechanism for DNA discoveredNirenberg, MatthaeiNational Institute for Health
1962Concept of restriction and modification enzymes bornArber, DussoixUniversity of Geneva
1962Sanger moves to the newly created Laboratory of Molecular Biology in CambridgeSangerLaboratory of Molecular Biololgy
October 18, 1962Watson, Crick and Wilkins won the Nobel Prize for Medicine for their work in determining the structure of DNAWatson, Crick, WilkinsLaboratory of Molecular Biology
1965Transfer RNA is the first nucleic acid molecule to be sequencedHolleyCornell University
1965Werner Arber predicts restriction enzymes could be used as a labortory tool to cleave DNAArberUniversity of Geneva
1965Atlas of Protein Sequence and Structure publishedDayhoffNational Biomedical Research Foundation
1965Ledley publishes Uses of Computers in Biology and MedicineLedleyNational Biomedical Research Foundation
1965Sanger and colleagues publish two-dimension partition sequencing methodSanger, Brownlee, BarrellLaboratory of Molecular Biology
1967First automatic protein sequencer developedEdman, BeggSt Vincent's School of Medical Research
1968 - 1970Restriction enzymes found to act as chemical knives to cut DNASmith, NathansUniversity of Geneva, University of California in Berkeley, Johns Hopkins University
1968The first partial sequence of a viral DNA is reportedWu, KaiserCornell University, Stanford University Medical School
1968Paul Berg started experiments to generate recombinant DNA moleculesBergStanford University
1969First principles for PCR publishedKhorana, KleppeUniversity of Wisconsin-Madison
1969New species of bacterium is isolated from hot spring in Yellowstone National Park by Thomas BrockBrockCase Western Reserve University
1969New idea for generating recombinant DNA conceivedLobhanStanford University
1970First complete gene synthesised KhoranaUniversity of Wisconsin
July 1970First restriction enzyme isolated and characterisedSmith, WilcoxJohns Hopkins University
1971Process called repair replication for synthesising short DNA duplexes and single-stranded DNA by polymerases is publishedKhorana, KleppeMIT
1971First plasmid bacterial cloning vector constructedBerg, Mertz, JacksonStanford University
May 1971Complete sequence of bacteriophage lambda DNA reportedWu, TaylorCornell University
June 1971First time potential biohazards of recombinant DNA raisedMertz, Berg, PollackStanford University
December 1971First experiments published demonstrating the use of restriction enzymes to cut DNADanna, NathansJohns Hopkins University
September 1972 - September 1972First time possible biohazards of recombinant DNA technology publicly discussedZinder
October 1972First paper published on generating recombinant DNABerg, Jackson, SymonsStanford University
November 1972First easy-to-use technique published for constucting recombinant DNA. J. Mertz, R. Davis, Proceedings of the National Academy of Science, USA 69/11, pp. 2270-74.Berg, MertzStanford University Medical School
November 1, 1972Nature editorial voiced concern about generating recombinant DNABerg, Jackson, SymonsStanford University
1973Recombinant DNA produced in bacteriaCohen, BoyerStanford University Medical School, University of California San Francisco
1973The sequencing of 24 basepairs is reportedGilbert, MaxamHarvard University
1974Regulation begins for recombinant genetic research
July 1974First concerns about potential biohazards of recombinant DNA publishedBerg, Baltimore, Boyer, Cohen
1975Temporary moratorium on genetic engineeringBerg
1975Sanger and Coulson publish their plus minus method for DNA sequencingSanger, CoulsonLaboratory of Molecular Biology
1976
April 1976Genentech foundedSwanson, BoyerGenentech Inc
1977Human growth hormone genetically engineered
1977Complete sequence of bacteriophage phi X174 DNA determinedSangerLaboratory of Molecular Biology
1977First computer programme written to help with the compilation and analysis of DNA sequence dataMcCallumLaboratory of Molecular Biology
February 1977Two different DNA sequencing methods published that allow for the rapid sequencing of long stretches of DNASanger, Maxam, GilbertHarvard University, Laboratory of Molecular Biology
1978Human insulin produced in E-coliGenentech
October 1978Nobel Prize for discovery and understanding of restriction enzymesArber, Nathans, SmithJohns Hopkins University, University of Geneva
1980Genetic engineering recognised for patenting
1980First patent awarded for gene cloningCohen, BoyerStanford University Medical School
1980Cesar Milstein proposed the use of recombinant DNA to improve monoclonal antibodiesMilsteinLaboratory of Molecular Biology
1980Sanger awarded his second Nobel Prize in ChemistrySanger, GilbertHarvard University, Laboratory of Molecular Biology
January 1980European Molecular Biology Laboratory convenes meeting on Computing and DNA SequencesEMBL
September 1980First transgenic mice made with recombinant DNA announced Barbosa, Gordon, Plotkin, Ruddle, ScangosYale University
September 1980First DNA sequence database createdDayhoffNational Biomedical Research Foundation
1980Largest nucleic acid sequence database in the world made available free over telephone networkDayhoffNational Biomedical Research Foundation
1981First genetically-engineered plant reported
1981First genetically cloned mice
1982Whole genome sequencing method is introduced for DNA sequencing
June 1982NIH agrees to provide US$3.2 million over 5 years to establish and maintain a nucleic sequence database
October 1982First recombinant DNA based drug approvedGenentech Inc
January 20, 1983Solomon Spiegelman diedSpiegelmanUniversity of Minnesota
1983Polymerase chain reaction (PCR) starts to be developed as a technique to amplify DNAMullisCetus Corporation
June 1984Results from PCR experiments start being reportedMullisCetus Corporation
1984First chimeric monoclonal antibodies developed which lays foundation for safer and more effective monoclonal antibody therapeuticsNeuberger, Rabbitts, Morrison, Oi, Herzenberg, Boulianne, Schulman, HozumiLaboratory of Molecular Biology, Stanford Univerity Medical School
March 1985Mullis and Cetus Corporation filed patent for the PCR techniqueMullisCetus Corporation
March 1985DNA fingerprinting principle laid outJeffreysUniversity of Leicester
December 20, 1985The Polymerase Chain Reaction technique was publishedMullisCetus Corporation
1986First machine developed for automating DNA sequencingHood, Smith, HunkapillerCalifornia Institute of Technology, Applied Biosystems
1986Human Genome Organization founded
May 1986First humanised monoclonal antibody createdDear, Foote, Jones, Neuberger, WinterLaboratory of Molecular Biology
June 1986Interferon approved for treating hairy cell leukaemia
June 1986First recombinant vaccine licensedMerck & Co
1988Campath-1H is created - the first clinically useful humanised monoclonal antibody.Winter, Waldmann, Reichmann, ClarkCambridge University, Laboratory of Molecular Biology
1988US Congress funds genome sequencing
April 1988Development of first rapid search computer programme to identify genes in a new sequencePearson, Lipman
April 1988First pitch for US Human Genome Project
October 1990Human Genome Project formally launched
1992GenBank is integrated into the NIH National Center for Biotechnology Information
November 1, 1993Severo Ochoa diedOchoaNew York University
December 1993Recombinant human deoxyribonuclease approved by FDA for cystic fibrosisGenentech
1994First chimeric monoclonal antibody therapeutic approved for marketCollerCentocor, State University of New York
July 1995Craig Venter's team at The Institute of Genomics Research (TIGR) published the first complete sequence of the 1.8 Mbp genome of a free-living organism (the bacterium Haemophilus influenzae)VenterThe Institute for Genomic Research
1996Complete genome sequence of the first eukaryotic organism, the yeast S. cerevisiae, is published
1996Pyrosequencing is introduced for DNA sequencingRonaghi, NyrenRoyal Institute of Technology
January 10, 1997Alexander R Todd diedToddUniversity of Manchester
December 1997First humanised monoclonal antibody approved for marketQueenProtein Design Labs, Roche
May 1998Commercial Human Genome Project launchedVenterCelera Genomics
December 1998Complete genome sequence of the first multicellular organism, the nematode worm Caenorhabditis elegans, is publishedSanger Institute, Washington University
1999First human chromosome sequence published
November 16, 1999Daniel Nathans diedNathans Johns Hopkins University
2000Complete sequences of the genomes of the fruit fly Drosophila and the first plant, Arabidopsis, are published
June 2000Human genome draft sequence announced
October 4, 2000Michael Smith diedUniversity of British Columbia
December 2000First plant DNA sequenced
February 2001First consensus sequence of human genome publishedCelera
2002Complete genome sequence of the first mammalian model organism, the mouse, is published
July 2002Poliovirus synthesisedStony Brook University
October 2002Genomic sequence of the principal malaria parasite and vector reported
April 2003The sequence of the first human genome was published
July 28, 2004Francis H C Crick diedCrickLaboratory of Molecular Biology
October 5, 2004Maurice H F Wilkins diedWilkinsKing's College London
October 5, 2004First DNA microarray diagnostic device approved
February 2005Enzyme Ubp10 demonstrated to protect the genome from potential destabilising molecular eventsBerger, EmreWistar Institute
May 2006Last human chromosome is sequenced
October 26, 2007Arthur Kornberg diedKornbergStanford University
2008Structure of telomerase, an enzyme that conserves the ends of chomosomes, was decodedWistar Institute
January 2011DNA sequencing proves useful to documenting the rapid evolution of Streptococcus penumoniae in response to the application of vaccinesWellcome Trust Sanger Institute
June 2012DNA sequencing helps identify the source of an MRSA outbreak in a neornatal intensive care unitPeacock, ParkhillCambridge University, Wellcome Trust Sanger Institute
December 2012DNA sequencing utilised for identifying neurological disease conditions different from those given in the original diagnosisUniversity of California San Diego
March 2014Promising results announced from trial conducted with HIV patients
October 7, 2015Nobel Prize in Chemistry awarded to scientists for understanding the process of DNA repairLindahl, Modrich, SancarFrancis Crick Institute, Howard Hughes Medical Institute, University of North Carolina

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