Chapter 10: DNA

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Chapter 10 DNA

• Something to think about
• Look around the room at your classmates. Observe
  how they vary in the shape of their front
  hair-line, the space between their front teeth,
  the way in which their earlobes are attached to
  their head.
• Could these traits be inherited?
• How are traits passed from generation to
  generation?

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The Central Dogma of Molecular Biology

• Genes code ? enzymes ? perform functions in the
  cell that results in a phenotype
• DNA ? RNA ? Protein

Transcription
Translation
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10.1 Experiments showed that DNA is the genetic
material

• Biologists had to find out the chemical nature of
  genes.
• Griffith Transformation
• Factors in heat-treated harmful bacteria can be
  transmitted to harmless bacteria that dont cause
  disease
• Hershey-Chase
• Offered supporting evidence that genes are
  composed of DNA
• Showed that radioactive tagged DNA entered
  bacterial cells but radioactive tagged protein
  did not. Therefore genetic information is located
  in the DNA

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DNA and RNA are polymers ofNucleotides

• DNA Deoxyribonucleic Acid
• Found in the nucleus
• Three subunits
• Deoxyribose (5 carbon sugar)
• Phosphate
• Nitrogen Base (can be 1 of 4)
• Guanine
• Cytosine
• Adenine
• Thymine

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G pairs with C T pairs with A
Sugar-Phosphate Backbone
Nitrogenous Bases
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Purines and Pyrimidines
Purines Have two rings
Adenine Guanine
Pyrimidines Have one ring
Thymine Cytosine
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DNA is a double-stranded helix

• Chargaffs Rules
• Determined that the percent of guanine (G) and
  cytosine (C) are nearly equal in any sample of
  DNA the same was so for thymine (T) and adenine
  (A).
• X-Ray Evidence
• Rosalind Franklin took X-ray images of the DNA
  molecule that helped to develop the model for DNA
• The Double Helix
• Francis Crick and James Watson developed the
  double helix model of DNA

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DNA is a double-stranded helix

• A double helix looks like a spiral staircase.
• Hydrogen bonds hold the two strands of DNA
  together
• The As on one strand hydrogen bond to the Ts on
  the other, likewise for Gs and Cs
• Base pairing explains why the percentage As is
  the same as the percentage of Ts

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The shape of DNA is important because

• Our DNA makes up 1 of our body weight, so a 150
  lb. person would have 1.5 lbs. of DNA.
• In one cell 3 meters of DNA.
• If you typed out your entire DNA sequence in
  Times 12pt font you would fill enough paper to
  reach the top of the Washington Monument in D.C.

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DNA Replication
Video

• It has not escaped our notice that the specific
  pairing we have postulated immediately suggests a
  possible copying mechanism for the genetic
  material Watson and Crick
• The semi conservative model when a double helix
  replicates, each of the two daughter molecules
  will have one old strand (parental or template)
  and one new strand.

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DNA Replication
Video

• Step 1 Double helix unzips
• Replication begins at origins of replication
• Helicase unzipping enzyme
• H-bonds break
• Replication fork the point at which the two
  strands split
• Step 2 Each original strand becomes a template
  strand (white)
• Complementary bases fill in from the 5 end to
  the 3 end (opposite directions)
• DNA polymerase building enzyme adds new bases
• Step 3 Proofreading by DNA polymerase

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DNA Replication
Enzyme (Helicase) Unzips
T A A G C
A T T C G
T A A G C
New Strands
T A A G C
Enzyme (DNA Polymerase) fills in new nucleotide
bases
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The molecular basis for traits

• An organisms genotype is its genetic make-up
• A phenotype is the organisms specific trait.
• For example the gene OCA2 causes the albino
  phenotype
• The DNA specifies traits by providing the
  instructions on how to make protein.

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The Chain of Command In the Cell

• DNA ? RNA ? Protein
• Genes code ? enzymes ? perform functions in the
  cell that results in a phenotype

Transcription
Translation
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The one gene one enzyme hypothesis

• Beadle and Tatum determined that mutant mold
  strains were defective in a single gene for each
  type of mutant
• Their hypothesis that there is one gene for every
  enzyme was correct except it wasnt just for
  enzymes it was discovered that there is one gene
  for every protein. Further, scientists discovered
  that there are some proteins made of several
  polypeptides so again they changed the hypothesis
  to one gene one polypeptide.

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RNA Structure

• RNA Ribonucleic Acid
• Single stranded!
• Can leave the nucleus
• Monomers made of
• Ribose (5 carbon sugar)
• Phosphate
• Nitrogen Base (1 of 4)
• Guanine
• Cytosine
• Adenine
• Uracil (Instead of Thymine)

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Three Kinds of RNA

• Messenger RNA (mRNA)
• conveys genetic information from the DNA in the
  nucleus to the rest of the cell
• Ribosomal RNA (rRNA)
• structural, part of ribosome
• Transfer RNA (tRNA)
• carries amino acids to site of protein synthesis,
  it is a material transporter (not for information)

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Genetic information written in codons is
translated into amino acid sequences

• RNA is a complementary copy of a DNA template
  strand instead of As pairing with Ts such as
  in DNA replication, the As in DNA pair with Us
  in RNA.
• The mRNA is then decoded into protein through a
  process called translation.
• Codons are groups of three nucleotide bases
• Each codon on mRNA codes for a specific amino
  acid.

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Transcription and Translation of Codons
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Transcription

• RNA polymerase creates the RNA sequence from the
  template DNA in the nucleus
• Three Stages
• Initiation RNA polymerase begins at the
  promoter sequence
• Elongation RNA strand peals away from the DNA
  template
• Termination RNA polymerase reaches the
  terminator sequence and detaches from the DNA

Animation
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Transcription
DNA rezips
Enzyme (Helicase) Unzips
RNA Leaves to go to a ribosome
T A A G C
RNA Strand
U A A G C
Enzyme (RNA Polymerase) fills in new nucleotide
bases
Template Strand
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CTAACCCTAACCCTAACCCTAACCCTAACCCTAACCCTCTGAAAGTGGAC
CTATCAGCAGGATGTGGGTGGGAGCAGATTAGAGAATAAAAGCAGACTGC
CTGAGCCAGCAGTGGCAACCCAATGGGGTCCCTTTCCATACTGTGGAAGC
TTCGTTCTTTCACTCTTTGCAATAAATCTTGCTATTGCTCACTCTTTGGG
TCCACACTGCCTTTATGAGCTGTGACACTCACCGCAAAGGTCTGCAGCTT
CACTCCTGAGCCAGTGAGACCACAACCCCACCAGAAAGAAGAAACTCAGA
ACACATCTGAACATCAGAAGAAACAAACTCCGGACGCGCCACCTTTAAGA
ACTGTAACACTCACCGCGAGGTTCCGCGTCTTCATTCTTGAAGTCAGTGA
ACCAAGAACCCACCAATTCCAGACACACTAGGACCCTGAGACAACCCCTA
GAAGAGCACCTGGTTGATAACCCAGTTCCCATCTGGGATTTAGGGGACCT
GGACAGCCCGGAAAATGAGCTCCTCATCTCTAACCCAGTTCCCCTGTGGG
GATTTAGGGGACCAGGGACAGCCCGTTGCATGAGCCCCTGGACTCTAACC
CAGTTCCCTTCTGGAATTTAGGGGCCCTGGGACAGCCCTGTACATGAGCT
CCTGGTCTGTAACACATTCCCCTGTGGGGATTTAGGGACTTGGGCCTTCT
GTCTTTGGGATCTACTCTCTATGGGCCACACAGATATGTCTTCCAACTTC
CCTACACAGGGGGGACTTCAAAGAGTGCCTTGAGCTGATCTGGTGATTGC
TTTTTTGTACTGTTATTTATCTTATTCTTTTCATTGTGAGGTACTGATGC
AAACACTTTGTACGAAAAGGTCTTTCTCATCTCGGGAGTCCCCGTCTATT
TGTCCCGGTCCCTGTTAACCCAGTCCCCGACAGGAGCCCCTTCTGCACCT
TGAGCTCTCACCACTCACCGTCCATCCAGCCCCAGCTCTGCCTGCAACCC
ACCCATCCCTGGGACTCGGGCCTCCCCTCTCTAGTGGTCTGGTCATCAGG
CCAGGGGCACGTGGAAGAAGCTATCGTGGCAAAGGGAGCAGTCATATCCC
CAAAATCTGTGGTTGGTTTACCACCACCATGGAAACCCCAGGGTGGGACT
CTAGTTTCAGGTTGGAGCTGAGCCCTGTCGGGAATGAGCTTTCCCCAGCT
ATGGCTTCTTGGGGCCCCTGTGCCCTGAGCTGTGTCTCCCAGCATCGGGT
CCCCACCATGCATATGGCCCACTCAGGCACAGTGCCGCGATGGCTGCATG
CGTGAGGGGGGCCTGGGCCCAGGGCTGGGAGTCCTTTGTGTCTCATGGCC
ATGATTGTCCTTCCGAGTATGATATGGTGGCCAATTTCTTTTATTCTGTC
GTTCAGAGTGAGTAAATGATGTAGAGTTCATGCAGAAAAAAATACAACAA
AAACCAAGGGAACATAGAATTGGAAAACGCGTCACAGCAATGAGTTAAAT
AGGTAACAAATTTCATCATTTGAAGAAAGACTTAGAGTGCCAAAAGTGCC
TCTTAAGTCTCCTTTAAAAAGTAGCAAAATTCATCCCTGAAGAAGCATCT
TGGCCTTTTTCATGTACTCAGAGTGCTGGTGAAGAACAAAGATTGCTGAA
ACATTATGTACCTAACAGCGTTACAGGGTGTAGATAACACACTGGAAAAC
CTGGTCGTTACAGTGGACATATTCCAGGAAGTCCTTGCCTGAGGTTTTCC
AAGTTATGGAATTGCTTGAGATTGGAAGAGGCGATGGAGGGTACAACTGT
AATGCCCAACCTCATTTTTGCTAACCCTGTTTTTAGACTCTCCCTTTCCT
TCAATCACCTAGCCTTCTTTCCACCTGAAAGGACTCTCCCTTAACTGAGA
GAACCGGACAGACTCCATCTTGGCTCTTTCACTGGCAGCCCCTTCCTCAA
AGACTTAACTCGTGCAAGCTGACTCCCAGGACATCCGAGAATGCAATTAA
CTGACAACCTACTGTGGCGAGCTACATCCGCAGTCCCCAGGAATTCGTCC
GATTGATAACGCCCAATTACCCGCGTCTATCACCTTGTAATAGTCTTAAA
GCACCTGCACCTGGAACTGTTTACTTTCCTGTAACCATTTATCCTTTTAA
CATTTTGCCTGATTTACTTATGTAAAATTCTTTTAACTAGACCGCCACTC
CCCTTTCTAAACAAAAGTATAAAAGAAAATCTAGCCCCTTCTTTGGGACT
GAGACAATTTTGAGGTTAACGCAGGGTGCCTGTAATCCTAAGGGAGGAGA
CCGCCACTTCTGCTGCCCTTCCCTTCCCCACACCCCCTTCTCTAGTTTAT
GAAACAGGGAAAAAGGGAGAAAGCAAAAAGATAAAAAAAACAGAAGTAAG
ATAAATAGCTAGACGACCTTGGCAGCACCACCCGGCACTGGTGGTTAAAA
TAATAATAATAATAATATTAACCCCTGACCTAAACTACTTGTGTTATCTG
TAAATTCCAGACACTGTATGAGGAAGCCCTGCAAAACTTTCTGTTCTGTT
ATCTGATGCGTGTAGCCCCCAGTCACGTTCCGATGCTTGCTCGATCTATC
ACGACCCTTTCAAGTGAACCCCTTAGAGTCGTAAACCCTTAAAAGGGCCA
GGAATTTCGTTTTCGGGGAGCTCGGCTCTTCAGGCCCAAGTAAACCTGCC
GTATCTCACCTGAGACCAACCCCCAACTACAAAACTCAACCTGGAATTTT
CCCAGGACCAAACCCATCTATATTCTGTAACCCGAAACCTCAAAGCCTAA
CCCTAACCCTAACCCCTACAGTTGAGGTCCCCCCGCCCCTGTGGTTCCAG
CTCAAGACAACCTGCCCCTCCGTGGGTTTGCAGGCCCTCTGGTGGGGGTG
GGAGCTGGGGGCCACATACAGCTCTCTGAGCTTAAGCCATTTTCTTCCTT
CATTCCTTCCTTCCTCCCTCCCTTCCCTTCCTTCCTCCCTCCCTCCCTCC
TTCCCTCCCTCCCTTTTTTTTTTCAGGGTCTTGCTCTGTCACCCAGGCTG
GAGTGCAGTGGCATGATCACAGCTGACTGCAGCCTCGGACTCCCAGGCTC
AAGTTATCTTCCCTCCTCAGCCTCCAGAGTAGGTGGGACTACAGGAGTGT
GCCATCGCACCCAGCGAATTTCTTAATTTTTATTTTGTAGAGATGAGGCC
TCTCGATATTGTCCAGGCTTGGAAGTAGTTCTTGAAATTCAAGAGGATCT
TGAAGTTCTGACCTCCTGTCAATATCCCTTCCCCTCACCTTGACCCTCCC
ATTCTGCCCCACCTGTCAGGATCACAAGGACCCCCAGATCAGCAGATGGG
AACCGGACCAAAAAGAGAAATAGTGCTGTCCCGCCCATAAGTACCACCCC
CAGACTCCCTGCTCCACCCTCTGGACCACAGGGAGGCCCCATGCTCCATC
CCTGAAAACCACCCCCAGACCCCCTGCTCCTCCCCACGGGACCGCCCCCA
GATCCACTGTTCCTGTCCTCCGGACCACACCGGACAGCTCCTTCCCTCGG
CGCCATCCCCAGACCCCAGCTCCTCCCCTCAGGATCATCCCCAGACCCCC
GCTCCTCCCATCAGGACCGCCCCCAGAACCCCCTGCTCCTCCCCACAGGA
CCACCCCCAGACCCCCGCTCCTCCCCTAAGGACCACCCACAGACCCCCAC
GCTTCCCCTCGGGACCACCCCCAGACCCCCGCTCCTCCCCTCAGGACCAC
CCCCAGATCCACTGTTCCTGTCCTCCGGACCACACCAGACAGCTCCTTCC
CTCGGCGCCATCCCCAGACCCCCACGCTTCCCCTCGGGACCACCCCCAGA
CCCCCGCTCCTGCCCTCGGGACCACGCCCAGACCCCCTGCTCCTCCCCAC
GAAACCACGCCCAGTAACCCCCCTCTTCTCCCCTCAGGACCACCCCCAGA
CCCCCGCTCCTCCCCTGGGAACCACCCCCAGACCCCCTGCTCCTCCCCAC
GAAACCACCCCCAGACTCCCTGCTCCTGTCCTCCGGACCACGCGACTGCT
CCTTCCCTCAGCGCCACCCCCAGACTGCCGCTCCTCCTGTCGGGACCCCC
TGAGGCTTTCTCCACCCGGAGTGCGGGGTAGGGAGCAGACGGAGAGTGAC
GGAGGGTGACGGAGAGTGACGAAAGTAGACGATGTCTGACGGAGAAGAGC
CGAGCGGAGCTGAAGGGCGGCGGAGAGTGACGGAAAGTGGCGAGAATTGA
CGGAAAGTGACGGGGACTGACGGACAGTGACGAAGAGTCACGAAATTTAT
CAGAGGGCGACAAAGAGGAAAGCGAAATGGTGAGATGCAGCCGGCCGAGC
CTAATCGGAGATGACGGAAAGTGACGGAGAGGAACGAGGAGTAAAGAGGG
GTGACGAAAAGAGCCGAAGCTGGTGGAGGCGAAGAACTGAGTGAGGGAAG
ATAGCCGAGATTAGCGGGTGGGCTGCAGCCGGGGCAGTCGCCCGAATGGG
CGGGACCCCACGGAGTTAGCGAGAGGATGCGAACAGCGGCCAGCCGGGCA
GCACGCGAGCGAGGGAGGGCGTGGAGGGCCGTGGGTCCGCCTGCACTGAG
GCAGGCATGCGTGGCACCGAGGTGACCCGGGTGGGAGGTGCACCGCCGCC
CCCTGGCAGTCTCTCCGCGGAGCCCAAGCCCGTCTTCTCCGCCCCTTTGC
AGACCTCGGCGCCCAGCCTGGCCCCTGACGCCCACCCGCGGCCCCACCCA
GCGCCCGGGCCCACGAGGCCGAGGAGCGGCGGAGACTAACGGCCCCTGGA
CCCCAGGCAGCACATGGCCCAGAGCATCCCAGCCCAGTGGAGGGCGGCAC
ATGGCGGGAGGGCGGGAGTCCGTGTCCACTCATGGCCGGGGAGGGGAGGG
CAAGTTCTGGTGGCTGGGGAGGCCTAGAGCATCACAGCCCAGTGGAGGGC
TGCACATGGCAGGGGAGGGGAGAGCAAGAGTGTGCGGGCGAGGGAGGAGA
GGGCAAGACTGCGTGTCCGCTCCAGTCTCTCTTCCTCATCTTATAAAGCC
ACGAGTCCCATGACTGGGGACCCAACCTAATAACATTATCTAATCCTAAT
TGCCTCCCAAAGGCCATATCTCCAATCAGGACATGAATTCGGGGATTAAA
TTGCCAACACATGGCTGGGCGCGATGGCTTGTGCTTTTTTTTTTTTTTTT
TTTGAGACGGAGTCTCGCTCTGTCGCCCAGGCTGGAGTGCAGTGGCGCTA
TCTCGGCTCACTGCAAGCTCTGCCTCCCGGGTTCACGCCATTCTCCTGCC
TCAGCCTCCTGAGTAGCTGGGACTACAGGCGCCCGCCACCACGCCCAGGT
AATTTTTTTTTTTTTTTTTTTGTATTTCTTTGTAGAGACGGGGTTTCACC
ATGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCACCCATCTC
GGTCTCCCAAAGTGCTAGGATTGCAGGCCTGAGCCACCGCACCCAGCTGC
CTTGTGCTTTTAATCCCAGCACTTTCAGAGGCCAAGGCAGGCGATCACCT
GAGGTCAGGAGTTCAAGACCAGCCTGGCCAACATGGTGAAACCCCATCTC
TAATACAAATACAAAAAAAAAACAAAAAACGTTAGCCAGGAATGAGGCCC
GGTGCTTGTAATCCTAAGGAAGGAGACCACCACTCCTCCTGCTGCCCTTC
CCTTCCCCACACCGCTTCCTTAGTTTATAAAACAGGGAAAAAGGGAGAAA
GCAAAAAGCTTAAAAAAAAAAAAAAAAAAACAGAAGTAAGATAAATAGCT
AGATGATCTTGGCAGCACCACCCGACCCTGGTGGTTAAAATAATAATAAT
AATAATATTAACCCCTGACCTAAACTACTTGTGTTATCTGTAAATTCCAG
ACACTGTATGAGGAAGCCCTGCAAAACTTTCTGTTCTGTTATCTGATGCG
TGTAGCCCCCAGTCACGTTCCCCATGCTTCCTCGATCTATCACAACCCTT
TCACGTAAACCCCTTAGAGTTGTAAACCCTTAAAAGGGCCAGGAATTTCG
TTTTCGGGGAGCTTGGCTCTTCAGGCGCAAGTGTGCCGATGCTCCTGGCA
GAGTAAAGCCCTTCCTTCTTTAACCCAGTGTCTGAGGAATTTTGTCTGCG
GCTTGTCCTGCCACAATGCCAGCTACCAGGAGGCTGAGGTGTGAGAATCG
CTCGAACCTGGGAGGCAGAGGTTGCAGCGAGCCGAGATCCCACGATTGCA
CTCCAGCCTGGGTGATAG
This DNA sequence will make a protein, however
not all of it will. Some of it is nonsense and
some of it gives information about when the
protein should be made where it should be sent,
etc.
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Post Transcriptional RNA Modification

• mRNA is edited before it makes protein
• Introns (garbage)
• Exons (the expressed genes)
• mRNA also sometimes gets caps and tails before
  leaving the nucleus
• Protect the RNA
• Help it bind to a ribosome

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The Genetic Code

• Within the DNA is a code to make proteins
• The genetic code is the set of rules that
  determines which codon codes for each amino acid
• Redundancy but no Ambiguity
• Start codon AUG
• Find the stop codons

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(No Transcript)
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A Proteins Shape Determines its Function

• Most enzymes are globular with a place the shape
  of the substrate where the substrate binds
  (active site).
• Structural proteins (hair and tendons) are long
  and thin.

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A Proteins Shape Depends on Four Levels of
Structure

• Primary Structure the sequence of amino acids
• Secondary Structure the protein folds into
  local patterns.
• Alpha helix
• Beta sheet
• Tertiary Structure the overall,
  three-dimensional shape of the protein.
• Quaternary Structure the combination of peptide
  chains (sub-units) that form the entire protein.

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(No Transcript)
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Translation
Firefly Movie

• Ribosomes read mRNA and assemble polypeptides
• mRNA is the message that comes directly from DNA
  (pink)
• tRNA brings amino acids and matches them with the
  correct codon on mRNA (green)
• tRNAs anti-codon is complementary to the mRNAs
  codon
• tRNA enters the ribosome and drops off an amino
  acid (purple)
• Amino acid binds with the growing polypeptide

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Translation

• Initiation Translation begins at an AUG (start
  codon) the tRNA binds with the anti-codon UAC
• Elongation Amino acids are added to the
  polypeptide chain until a stop codon is read
• Peptide bonds are formed between each pair of
  amino acids
• Termination a stop codon is read by a tRNA
  carring no amino acid

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Translation
Translation Animation
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Gene Regulation

• Not all genes are expressed in every cell
• Not all genes are expressed at the same time.
• An operon is a group of genes that operate
  together
• A skin cell expresses different genes than a
  nerve cell

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Gene Regulation
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Mutations change the meaning of genes

• A mutation is any change in the nucleotide
  sequence
• Two types
• Point mutations when one base is substituted
  for another
• Frameshift mutations when a base is added or
  deleted (the entire reading frame is changed)

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• Point mutations (Substitutions)
• Original The fat cat ate the wee rat.
• Point Mutation The fat hat ate the wee rat.
• Frameshift mutations (Insertion, Deletion)
• Original The fat cat ate the wee rat.
• Frame Shift The fat caa tet hew eer at.

Deletion
Substitution
Insertion
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What causes mutations?

• Spontaneous mistake (natural)
• Mutagens a physical or chemical agent
• Physical
• Radiation
• Chemical
• Nicotine
• Agent-Orange
• Benzene
• Bromine

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What do mutations cause?

• Diversity!
• Genetic Disease
• Sickle cell anemia
• Cystic fibrosis
• Huntingtons disease
• Cancer