The Molecular Basis for Inheritance

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Chapter 16

• The Molecular Basis for Inheritance

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• Characteristics of Genetic Material
• replication
• storage
• expression
• variation
• Genetic Material Protein or Nucleic Acid?

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• Evidence Favoring Proteins
• Great specificity of function
• Little was known about nucleic acids
• A key factor in determining the identity of the
  genetic material was the choice of appropriate
  experimental organisms
• The role of DNA in heredity was first worked out
  by studying microbes
• Bacteria and viruses

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• Evidence Favoring DNA
• Transformation Studies Griffith then Avery,
  McLeod and McCarty
• Hershey and Chase
• Indirect evidence from eukaryotes
• Recombinant DNA technology has provided empirical
  evidence that DNA is the genetic material in most
  organisms. A few organisms possess RNA as the
  genetic material.

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• Additional evidence came from studies using a
  bacteriophage
• virus that infects bacteria
• Phages are widely used as research tools in
  molecular genetics
• Viruses are much simpler than cells
• little more than DNA enclosed by a protein coat
• To reproduce, a virus must infect a cell and take
  over the cells metabolic machinery

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• Injected DNA provides genetic information that
  makes the cells produce new viral DNA and
  proteins, which assemble into new viruses.
• Provided evidence that nucleic acids, rather than
  proteins, are the hereditary material, at least
  for viruses

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• Indirect Evidence From Eukaryotes That DNA Is the
  Genetic Material of Cells
• Prior to mitosis, a eukaryotic cell exactly
  doubles its DNA content, and during mitosis, this
  DNA is distributed exactly equally to the two
  daughter cells
• Nucleic Acids DNA and RNA
• Polymers of nucleotides
• Each nucleotide has
• phosphate group
• pentose sugar ribose in RNA and deoxyribose in
  DNA
• nitrogenous base purines (AT) and pyrimidines
  (CG)

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• Chargaff found a peculiar regularity in the
  ratios of nucleotide bases
• the number of adenines approximately equaled the
  number of thymines, and the number of guanines
  approximately equaled the number of cytosines
• In humans the bases are present in these
  percentages
• A 30.9 and T 29.4
• G 19.9 and C 19.8
• Remained unexplained until the discovery of the
  double helix
• Chargaffs rules

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• Structure of DNA Watson and Crick double helix
• How could the structure of DNA could account for
  its role in inheritance.
• The arrangement of covalent bonds in a nucleic
  acid polymer was well established
• researchers began to focus on discovering the
  three-dimensional structure of DNA

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• In April 1953, Watson and Crick surprised the
  scientific world with their molecular model for
  DNA the double helix, which has since become the
  symbol of molecular biology.
• In a second paper that followed their
  announcement of the double helix, Watson and
  Crick stated their hypothesis for how DNA
  replicates

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• Two major sources of information used by Watson
  and Crick to determine DNA structure
• Base composition analysis conducted by Chargaff
• X-ray diffraction studies conducted by Ashbury
  and Franklin
• Crystallographers use mathematical equations to
  translate patterns into information about the
  three-dimensional shapes of molecules

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• Complementary base pairs
• Adenine and guanine are purines, while cytosine
  and thymine are pyrimidines
• Watson tried bases paired like-with-like--for
  example, A with A and C with C but this model did
  not fit the X-ray data
• A purine-purine pair is too wide and a
  pyrimidine-pyrimidine pair too narrow to account
  for the diameter of the double helix
• The solution is to always pair a purine with a
  pyrimidine
• The Watson-Crick model explained Chargaffs rules

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• Features of the Watson-Crick Model of DNA
• 1. Two long polynucleotide chains coiled around
  a central axis, forming a right-handed double
  helix
• 2. The two chains are antiparallel
• 3. Bases are flat, lying perpendicular to
  central axis, stacked on top of each other 3.4
  angstroms
• 4. Nitrogenous bases on opposite chains are
  paired as a result of hydrogen bonding
• 5. Each complete turn of the helix is 34
  angstroms
• 6. Alternating larger major grooves and smaller
  minor grooves.
• 7. Diameter is 20 angstroms

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• DNA Replication
• Semi-conservative Replication
• Origin of replication
• Replication fork
• Template

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• The two DNA strands are antiparallel
• At the 3' end, a hydroxyl group
• The 5' end terminates with the phosphate group
• During the process of replication, the new
  nucleotides are added to the 3' end of the
  growing strand

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• Enzymes involved in DNA replication
• Helicase
• Primase
• DNA Polymerase III
• DNA Polymerase I
• Topoisomerase
• DNA ligase
• Single-strand binding proteins

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• DNA synthesis in prokaryotes
• Step 1. Unwinding
• Step 2. Initiation
• Step 3. Elongation of leading and lagging strands
  
• Step 4. Completion of lagging strand
• Okazaki fragments joined
• Step 5. Proofreading

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• Mismatched nucleotides sometimes evade
  proofreading
• May arise after DNA synthesis is completed--by
  damage to a nucleotide base
• Nucleotide excision repair
• Segment cut out (excised) by nuclease and the gap
  is filled in with correct nucleotides by DNA
  polymerase and ligase

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• In Eukaryotes
• synthesis originates in multiple sites
• more DNA polymerase
• synthesize entire genome faster
• DNA polymerases are different
• Contain telomeres at the ends of DNA

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• Add nucleotides only to the 3' end which provides
  no way to complete the 5' ends of daughter DNA
  strands
• produce shorter and shorter DNA molecules
• Prokaryotes avoid this with circular DNA
• Eukaryotes special nucleotide sequences called
  telomeres at the ends that do not contain genes
• After multiple generations, organisms need a way
  to restore shortened telomeres
• Telomerase catalyzes lengthening of telomeres

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