Chapter 12 Molecular Genetics

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Chapter 12 Molecular Genetics

• 12.1 DNA The Genetic Material

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Discovery of the Genetic Material

• Chromosomes are about 50 nucleic acid and 50
  protein, which is the genetic material?
• Most scientists thought that protein was the
  genetic material because protein is more complex
• Griffith performed the first major experiment
  that led to the discovery of DNA as the genetic
  material

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Discovery of the Genetic Material
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Discovery of the Genetic Material

• Significance of Griffiths work (1928)
• One strain of bacteria transformed into another
  strain
• Did not identify what the transforming substance
  was

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Discovery of the Genetic Material

• 1944 Oswald Avery identified that DNA was the
  transforming substance in Griffiths experiments
• Most leading scientists did not believe him

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Discovery of the Genetic Material

• 1952 Hershey and Chase used radioactively labeled
  DNA and radioactively labeled protein and proved
  that DNA is the genetic material

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DNA Structure

• DNA is made of subunits called nucleotides
• Three parts to a DNA nucleotide
• Sugar
• Phosphate
• Nitrogen Base

NUCLEOTIDE
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DNA Structure

• Four Different Nitrogen Bases
• Purine (two rings)
• Adenine
• Guanine
• Pyrimidine (one ring)
• Cytosine
• Thymine
• Uracil (not found in DNA)

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DNA Structure Chargaffs Rule

• Chargaff determined in 1950 that the amount of
  adenine equals the amount of thymine and the
  amount of guanine equals the amount of cytosine
• Chargaffs Rule AT and CG

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DNA Structure X Ray Diffraction

• Rosalind Franklins (1951) famous photo of X ray
  diffraction of DNA

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DNA Structure Double Helix

• In 1953 Watson and Crick astounded the scientific
  community with their announcement of DNAs
  structure

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DNA Structure Double Helix

• Watson and Crick, using Franklins photo,
  determined that DNA is a double helix with
• Outside strands of alternating sugar and
  phosphate
• C bonds with G with three hydrogen bonds
• A bonds with T with two hydrogen bonds

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DNA Structure Double Helix

• DNA called a twisted ladder
• Sugar is deoxyribose in the upright rails of the
  ladder alternating with phosphate (spacers)
• Rungs of the ladder have a purine base H-bonded
  to a pyrimidine base

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DNA Structure Double Helix

• DNA strands are antiparellel (one strand right
  side up and other stand upside down)
• Stands named by their Carbon orientation, C-5
  (5) or C-3 (3)

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Chromosome Structure

• An average sized chromosome would be 5 cm long if
  the DNA were stretched out
• DNA is packaged to be condensed in the cells
  nucleus

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Chapter 12 Molecular Genetics

• 12.2 Replication of DNA

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Semiconservative Replication

• DNA original stand untwists
• New base pairs bond to open existing stands
  following base paring rules (AT, CG)
• New strands twist each new helix is half new
  half original

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Enzymes Control DNA Replication Enzymes Control
DNA Replication

• Untwisting by DNA helicase
• Strands kept apart by single-stranded binding
  proteins
• Add starter RNA segment by RNA primase
• Add new nucleotides by DNA polymerase
• This is only the highlights there are many other
  enzymes involved

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DNA Replication

• Because DNA is antiparallel and new nucleotides
  can only be added to the 3 end, each strand
  replicates slightly differently

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DNA Replication

• Leading strand replicates by continuous addition
  of nucleotides to the 3 end
• Lagging strand replicates by producing short DNA
  sections called Okazaki fragments
• Enzyme ligase glues the fragments together

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Comparing DNA Replication in Eukaryotes and
Prokaryotes

• Eukaryotes have multiple areas of DNA replication
  along one chromosome
  
• Prokaryotes have one circular chromosome and have
  only one origin of replication

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Chapter 12 Molecular Genetics

• 12.3 DNA, RNA, and Protein

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Central Dogma

• How does the information in DNA, located in the
  nucleus, allow for the production proteins in the
  cytoplasm?
• RNA is another form of nucleic acid that relays
  the information.

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RNA versus DNA

• RNA
• Single helix
• Ribose sugar
• Bases adenine, guanine, cytosine, and uracil
• Several types of RNA

• DNA
• Double helix
• Deoxyribose sugar
• Bases adenine, guanine, cytosine, and thymine
• One type of DNA

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RNA versus DNA
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Types of RNA

• Messenger RNA (mRNA) long strands (hundreds of
  nucleotides) that are formed complementary to
  DNA leave the nucleus to carry information to
  the cytoplasm
• Transfer RNA (tRNA) short (80-100 nucleotides)
  T-shaped RNA that transport amino acids
• Ribosomal RNA (rRNA) along with protein make up
  the ribosomes
• There are several other types of RNA also each
  with a specific function.

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Types of RNA
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DNA to RNA to Protein

• Two step process transcription and translation
• Transcription (rewrite) RNA is made from DNA
  occurs in the nucleus
• Translation (change language) protein is made
  from RNA code occurs in the cytoplasm at the
  ribosome

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Transcription

• A section DNA (ave. size 8000 nucleotides) in the
  nucleus untwists and unzips.
• RNA nucleotides, following base pairing rules,
  bond on the leading strand of DNA
• Like DNA replication controlled by many enzymes

Occurs in the nucleus
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RNA Processing

• RNA when it is transcribed must be processed
• GTP cap is added to 5 end to protect and give
  attach signal to ribosome
• Introns (intervening sequences) are cut out
• Exons (expressed sequences) are put together
• Poly-A tail (30-200 A nucleotides) added to 3
  end to protect and get out of nucleus signal

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Translation Making Protein

• Starts when mRNA, tRNA carrying amino acids, and
  small and large ribosomal subunits come together
• Concludes when a polypeptide chain in produced

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The Code

• There are 20 amino acids, each is coded for by a
  sequence of 3 nucleotides called a codon.
• Discovered during the 1960s.

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The Code
mRNA Genetic Code

• mRNA has the codon
• tRNA has the anticodon (complementary to the
  codon)
• Example mRNA codon AUG would code for the amino
  acid methionine which is also the start codon
• Redundancy exists more that one codon per amino
  acid (UAU and UAC codes for tyrosine)
• Ambiguity does not exist UAU only codes for
  tyrosine not any other amino acid.

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Translation

1. All the players come together
2. First tRNA with anticodon UAC carrying methionine
   bonds with mRNA codon AUG at the P-site of the
   ribosome
3. Second tRNA with anticodon carrying another amino
   acid bonds with complementary mRNA codon at
   A-site of ribosome
4. Polypeptide bond forms between two amino acids
5. Ribosome moves down the mRNA so that the first
   tRNA is now in E-site of ribosome (and is
   released)
6. A-site is now empty to attach the third tRNA
   carrying the third amino acid
7. Steps 4-7 repeated until mRNA codon for stop is
   signaled, then polypeptide chain released

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One Gene-One Enzyme

• The Beadle and Tatum experiment showed that one
  gene codes for one enzyme. We now know that one
  gene codes for one polypeptide.

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Chapter 12 Molecular Genetics

• 12.4 Gene Regulation and Mutation

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Prokaryote Gene Regulation

• Ability of an organism to control which genes are
  transcribed in response to the environment
• An operon is a section of DNA that contains the
  genes for the proteins needed for a specific
  metabolic pathway.

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Lac Operon
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Try Operon
What would an off Try operon look like?
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Eukaryote Gene Regulation

• Controlling transcription transcription factors
  ensure that a gene is used at the right time and
  that proteins are made in the right amounts
• Promoters stabilize binding of RNA polymerase
• Regulatory proteins control rate of
  transcription
• The complex structure of eukaryotic DNA also
  regulates transcription.

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Eukaryote Gene Regulation

• Hox genes are responsible for the general body
  pattern of most animals.
• Hox genes code for transcription factors that are
  active in zones of the embryo that are in the
  same order as the genes on the chromosome

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Eukaryote Gene Regulation

• RNA interference can stop the mRNA from
  translating its message.

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Mutations

• Mistakes occur in copying the DNA during
  replication.
• Mechanisms exist for correcting these mistakes
• If the mistakes are permanent then a mutation
  occurs
• If a mutation in the DNA occurs, then the protein
  that is made from this DNA instruction can be
  absent or nonfunctional.

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Mutations
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Mutations
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Types of Mutations
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Chromosomal Mutations

• Pieces of chromosomes get deleted, duplicated,
  inverted, inserted or translocated
• Visible on karyotype

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Chromosomal Mutations

• Fragile X chromosome is due to about 30 extra
  repeated CGG codons near the tip of the X
  chromosome
• Results in many mental and behavioral symptoms

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Protein Folding and Stability

• Incorrect amino acid sequences can lead to
  changes in the shape and thus the function of
  proteins

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Causes of Mutations

• Mutagens are agents that cause mutations
• Spontaneous no known cause wrong nucleotide
• Occurs 1/100,000 base pairs
• Remains unfixed less than one in one billion

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Causes of Mutations

• Chemicals like asbestos, benzene, formaldehyde,
  multiple agents in cigarette smoke, and many
  others
• Affect DNA by changing chemical nature of the
  bases
• May resemble nucleotides and bond in place of the
  DNA nucleotides preventing DNA replication

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Causes of Mutations

• Radiation high energy rays like X rays and gamma
  rays form free radicals (charged escaped
  electrons) that damages DNA
• UV radiation can cause adjacent thymines to bind
  with each other instead of complementary
  nucleotides causing a kink in the DNA molecule
  which prevents replication

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Body Cell versus Sex Cell Mutation
Molecular Genetics

• Somatic cell mutations are not passed on to the
  next generation.

• Mutations that occur in sex cells are passed on
  to the organisms offspring and will be present
  in every cell of the offspring.