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DNA: The Genetic Material. Chapter 12. 3. The Genetic Material. Frederick Griffith, 1928studied Streptococcus pneumoniae, a pathogenic bacterium causing pneumoniathere are 2 strains of Streptococcus:S strain is virulent R strain is nonvirulentGriffith infected mice with these strains hoping to understand the difference between the strains.

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    1. Announcements Lab Final- This week over 2nd half of labs; DNA Fingerprinting handout Due Lecture Exam- Monday April 26 (11, 12, and sex-linkage) Final Exam- Monday May 3 @ 10:30 am Yearbook Sales-Tuesday, April 13, from 11 a.m. to 12:30 p.m. in Jean Silva’s office in Powell.  Sales will continue from 2:30-5 p.m $10 The Laramie Project April 21 @ 12:30 p.m. Also April 22 – 24 @ 7 p.m. All shows in Peterson 142, The Black Box Theatre Earth Week Activities next week The SGC Creative Writing class will hold a public reading in Laird Auditorium on Monday April 19 at 3:00 Students who are graduating this semester to take the ETS Proficiency Profile Survey-?Collins 224 Tuesday, April 20, 6-8 pm Thursday, April 22, 1:30-3:30 pm 1

    2. DNA: The Genetic Material Chapter 12

    3. 3 The Genetic Material Frederick Griffith, 1928 studied Streptococcus pneumoniae, a pathogenic bacterium causing pneumonia there are 2 strains of Streptococcus: S strain is virulent R strain is nonvirulent Griffith infected mice with these strains hoping to understand the difference between the strains

    4. 4 The Genetic Material Griffith’s results: live S strain cells killed the mice live R strain cells did not kill the mice heat-killed S strain cells did not kill the mice heat-killed S strain + live R strain cells killed the mice

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    6. 6 The Genetic Material Griffith’s conclusion: information specifying virulence passed from the dead S strain cells into the live R strain cells Griffith called the transfer of this information transformation

    7. 7 The Genetic Material Avery, MacLeod, & McCarty, 1944 repeated Griffith’s experiment using purified cell extracts and discovered: removal of all protein from the transforming material did not destroy its ability to transform R strain cells DNA-digesting enzymes destroyed all transforming ability the transforming material is DNA

    8. 8 The Genetic Material Hershey & Chase, 1952 investigated bacteriophages: viruses that infect bacteria the bacteriophage was composed of only DNA and protein they wanted to determine which of these molecules is the genetic material that is injected into the bacteria

    9. 9 The Genetic Material Bacteriophage DNA was labeled with radioactive phosphorus (32P) Bacteriophage protein was labeled with radioactive sulfur (35S) radioactive molecules were tracked only the bacteriophage DNA (as indicated by the 32P) entered the bacteria and was used to produce more bacteriophage conclusion: DNA is the genetic material

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    11. 11 DNA Structure DNA is a nucleic acid. The building blocks of DNA are nucleotides, each composed of: a 5-carbon sugar called deoxyribose a phosphate group (PO4) a nitrogenous base adenine, thymine, cytosine, guanine

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    13. 13 DNA Structure The nucleotide structure consists of the nitrogenous base attached to the 1’ carbon of deoxyribose the phosphate group attached to the 5’ carbon of deoxyribose a free hydroxyl group (-OH) at the 3’ carbon of deoxyribose

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    15. 15 DNA Structure Nucleotides are connected to each other to form a long chain phosphodiester bond: bond between adjacent nucleotides formed between the phosphate group of one nucleotide and the 3’ –OH of the next nucleotide The chain of nucleotides has a 5’ to 3’ orientation.

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    17. 17 DNA Structure Determining the 3-dimmensional structure of DNA involved the work of a few scientists: Erwin Chargaff determined that amount of adenine = amount of thymine amount of cytosine = amount of guanine This is known as Chargaff’s Rules

    18. 18 DNA Structure Rosalind Franklin and Maurice Wilkins Franklin performed X-ray diffraction studies to identify the 3-D structure discovered that DNA is helical discovered that the molecule has a diameter of 2nm and makes a complete turn of the helix every 3.4 nm

    19. 19 DNA Structure James Watson and Francis Crick, 1953 deduced the structure of DNA using evidence from Chargaff, Franklin, and others proposed a double helix structure

    20. 20 DNA Structure The double helix consists of: 2 sugar-phosphate backbones nitrogenous bases toward the interior of the molecule bases form hydrogen bonds with complementary bases on the opposite sugar-phosphate backbone

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    22. 22 DNA Structure The two strands of nucleotides are antiparallel to each other one is oriented 5’ to 3’, the other 3’ to 5’ The two strands wrap around each other to create the helical shape of the molecule.

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    24. 24 DNA Replication Matthew Meselson & Franklin Stahl, 1958 investigated the process of DNA replication considered 3 possible mechanisms: conservative model semiconservative model dispersive model

    25. 25 DNA Replication Meselson and Stahl concluded that the mechanism of DNA replication is the semiconservative model. Each strand of DNA acts as a template for the synthesis of a new strand.

    26. 26 DNA Replication DNA replication includes: initiation – replication begins at an origin of replication elongation – new strands of DNA are synthesized by DNA polymerase termination – replication is terminated differently in prokaryotes and eukaryotes

    27. 27 DNA Repair DNA-damaging agents repair mechanisms specific vs. nonspecific mechanisms Mistakes during DNA replication can lead to changes in the DNA sequence and DNA damage. DNA can also be damaged by chemical or physical agents called mutagens. Repair mechanisms may be used to correct these problems.

    28. 28 DNA Repair DNA repair mechanisms can be: specific – targeting a particular type of DNA damage photorepair of thymine dimers non-specific – able to repair many different kinds of DNA damage excision repair to correct damaged or mismatched nitrogenous bases

    29. Genes and How They Work

    30. 30 The Nature of Genes Early ideas to explain how genes work came from studying human diseases. Archibald Garrod studied alkaptonuria, 1902 Garrod recognized that the disease is inherited via a recessive allele Garrod proposed that patients with the disease lacked a particular enzyme These ideas connected genes to enzymes.

    31. 31 The Nature of Genes Evidence for the function of genes came from studying fungus. George Beadle and Edward Tatum, 1941 studied Neurospora crassa used X-rays to damage the DNA in cells of Neurospora looked for cells with a new (mutant) phenotype caused by the damaged DNA

    32. 32 The Nature of Genes Beadle and Tatum looked for fungal cells lacking specific enzymes. The enzymes were required for the biochemical pathway producing the amino acid arginine. They identified mutants deficient in each enzyme of the pathway.

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    34. 34 The Nature of Genes Beadle and Tatum proposed that each enzyme of the arginine pathway was encoded by a separate gene. They proposed the one gene – one enzyme hypothesis. Today we know this as the one gene – one polypeptide hypothesis.

    35. 35 The Nature of Genes The central dogma of molecular biology states that information flows in one direction: DNA RNA protein Transcription is the flow of information from DNA to RNA. Translation is the flow of information from RNA to protein.

    36. 36 The Genetic Code Deciphering the genetic code required determining how 4 nucleotides (A, T, G, C) could encode more than 20 amino acids. Francis Crick and Sydney Brenner determined that the DNA is read in sets of 3 nucleotides for each amino acid.

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    38. 38 The Genetic Code codon: set of 3 nucleotides that specifies a particular amino acid reading frame: the series of nucleotides read in sets of 3 (codon) only 1 reading frame is correct for encoding the correct sequence of amino acids

    39. 39 The Genetic Code Marshall Nirenberg identified the codons that specify each amino acid. RNA molecules of only 1 nucleotide and of specific 3-base sequences were used to determine the amino acid encoded by each codon. The amino acids encoded by all 64 possible codons were determined.

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    41. 41 The Genetic Code stop codons: 3 codons (UAA, UGA, UAG) in the genetic code used to terminate translation start codon: the codon (AUG) used to signify the start of translation The remainder of the code is degenerate meaning that some amino acids are specified by more than one codon.

    42. Timeline of Molecular history 1859 Charles Darwin – no clue about genes 1865 Gregor Mendel – lost until 1900 1869 Friedrich Mieshcer - DNA 1900 Hugo de Vries – rediscovers Mendel 1902 Archibold Garrod – genetic cause of a human disease 1902 Sutton and Boveri – chromosome theory 1920 T.H. Morgan – genes on chromosomes/ Sex-linkage 1913 A.H. Sturtevant – linkage map 1927 H.J. Muller – x-ray induced mutations 1928-F. Griffith- Transformation 1941 G. Beadle and E.L. Taum – one gene = one enzyme 1944 O.T. Avery, C. McLeod, Maclyn McCarty - proposed DNA = genes 1950 E, Chargaff – DNA base composition rules 1952-Hershey and Chase 1953 J.Watson, F. Crick, R.Franklin and M.Wilkins – DNA structure 1958 M. Messelson and F. Stahl – DNA replication 1961 S.Brenner, F.Jacob, M. Messelson – mRNA discovered 1966 M. Niernberg, G.Khoroana – Genetic code 1970 H. Smith – restriction enzymes 1972 P. Berg – first recombinant DNA 1973 H. Boyer, S.Cohen – first “cloned DNA” fragment 1977 W.Gilbert, F.Sanger – DNA sequencing – first virus sequenced 1981- first transgenic mammals 1985 Alec Jeffreys – DNA fingerprinting 1985 Kary Mullis – PCR amplification 1990 J.Watson Human Genome Project 1993 Huntinington’s Disease Group – first identified genetic disease gene 1995 C.VentnerH.Smith – base sequences of H. influenzae and M. genitalium 1997 I. Wilmut – cloned Dolly the Sheep 2000 Alain Fischer - first successful gene therapy trial 2003 Complete human genome sequenced

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