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1860s - G. Mendel described the basic principles of inheritance. 1866- E. Haeckel proposed that the nucleus contains the factors necessary for heredity.

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Presentation on theme: "1860s - G. Mendel described the basic principles of inheritance. 1866- E. Haeckel proposed that the nucleus contains the factors necessary for heredity."— Presentation transcript:

1 1860s - G. Mendel described the basic principles of inheritance E. Haeckel proposed that the nucleus contains the factors necessary for heredity F. Miescher described some of the chemical property of DNA (C 29 H 49 N 9 P 3 O 22 ). At that time proteins were supposed to be the hereditary material Altmann names "nucleic acids“ Walter Sutton proposes that chromosomes contain genetic material – All 4 bases in DNA now characterised, (incl. T & C) in roughly equal amounts Enzymes found to be made from proteins. Archibold Garrod proposes chromosomes affects enzymes Phosphate "backbone" proposed to connect DNA bases together Ribose sugar associated with DNA characterised F. Griffith experiments with rough (R) and smooth (S) strains of Streptococcus pneumoniae in mice Beadle and Tatum propose "one gene, one enzyme" hypothesis Avery, MacLeod, McCarty show DNA is "transforming" agent (e.g., genetic material). A brief history of Genetics

2 Alfred Hershey & Martha Chase demonstrate that DNA contains genetic material Postulation of a complimentary, double helical structure for DNA (by Watson and Crick) Chargaff & Davidson publish exhaustive set of three volumes on "The Nucleic Acids", describing in great detail their physical properties and characterisation Genetic experiments support hypothesis that genetic messages of DNA are conveyed by its sequence of bp Meselson and Stahl demonstrate that DNA replicates semi- conservatively. Isolation of the first enzyme (DNA polymerase I) by A. Kornberg Discovery of RNA polymerase Discovery of messenger RNA The triplet nature of the genetic code is discovered. Monad and Jacob propose operon model of gene regulation Appreciation that genes conveying antibiotic resistance in bacteria are often carried on small bits of extrachromosomal DNA (plasmids) Establishment of complete genetic code Isolation of the enzyme DNA ligase Isolation of the first restriction enzyme.

3 Temin and Baltimore report the discovery of reverse transcriptase in retroviruses Use of ligase to link together restriction fragments. First recombinant molecules generated Eukaryotic genes are cloned in bacterial plasmids Retroviral oncogenes are identified as the causative agents of transformation DNA sequencing becomes possible. Interrupted genes are discovered and splicing of their transcripts is inferred Production of first human hormone (somatostatin) using recombinant DNA methods Cellular oncogenes are discovered by transfection Catalytic activity of RNA is discovered. Transgenic mice and flies are obtained by introducing new DNA into the germ line First version of "GenBank" created for storage of DNA sequences Proposal of Intramolecular Triplex structure for certain purine rich DNA sequences Polymerase Chain Reaction (PCR) technique first used First BACTERIAL genomes completely sequenced. (Haemophilus influenzae and Mycoplasma genitalium).

4 Genome of first EUKARYOTE completely sequenced. (Saccharomyces cerevisiae, 13,000,000 bp on 16 chromosomes) Dolly the Sheep cloned. E.coli genome sequenced. 2002/03 - Genome of Pasmodium (30 MB), Caenorhabditis elegans (100 Mb), Arabidopsis thaliana (100 Mb), Drosophila melanogaster (120 Mb), Mus musculus (300 Mb) have been completely sequenced The Homo sapiens genome (3000 MB) is sequenced – Full Genome sequencing. The Genomics and Post-Genomics age.

5 The transforming principle is DNA (F. Griffith experiments, 1928) The discovery of the genetic material Streptococcus pneumoniae strains  R (rough) and S (smooth)

6 1944 – O.T. Avery, C. MacLeod and M. McCarty experiments The DNA as transforming principle Chemical composition Prep. N. C H N P 37 34,27% 3,89% 14,21% 8,57% 42 35,50% 3,76% 15,36% 9,04% DNA 34,2% 3,2% 15,32% 9,05% I passaggi fondamentali nei protocolli attualmente disponibili sono:

7 The mechanics of inheritance

8 Alfred Hershey and Martha Chase experiments with T2 bacteriophage in E. coli T2 bacteriophages infecting an E.coli cell

9 Il modello proposto da Watson e Crick per la struttura della doppia elica del DNA 1) Scoperta del DNA (Miescher, 1869). Caratterizzazione delle 4 basi azotate ( ). Lo scheletro che connette le basi azotate è formato da gruppi fosfato (1915). Il ribosio è associato con il DNA (1927). Le principali tappe di una grande scoperta 2) Idrolisi del DNA, A/T = 1 C/G = 1 (Esperimenti di Chargaff). James Watson and Francis Crick

10 3) Diffrazione ai raggi X. I primi pattern di diffrazione risalgono al 1938 ma solo nel 1950 fu possibile ottenere foto di diffrazione ad alta risoluzione nel laboratorio di M. Wilkins. 2 periodicità  3,4 Å e 34 Å 4) La struttura ad  elica delle proteine (L. Pauling, 1951). 5) Elettrotitolazioni (basi legate da legami idrogeno). 6) Il legame fosfodiesterico 3’--5’ (A.L. Todd, 1952). Rosalind Franklin Maurice Wilkins

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