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Chapter 10
Gene Expression and Regulation
Chapter 10: Gene Expression / Regulation
HOW?
DNA contains information but is unable to carry out actions
Fact 1:
Proteins are the “workhorses” but contain no information
Fact 2:
Information in DNA must be linked with proteins
THUS
Substrate 1 Substrate 2 Substrate 3
Enzyme
A
Enzyme
B
Gene A Gene B
Beadle & Tatum: Bread mold experiments (1940s)
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Chapter 10: Gene Expression / Regulation
Figure 10.1 – Audesirk2 & Byers
Generally, one gene codes
for one protein (polypeptide)
How does information travel from DNA to ribosomes?
Structural Differences between RNA and DNA (See Table 10.1):
1) RNA is single-stranded
2) RNA has ribose sugar in backbone (DNA = deoxyribose)
Chapter 10: Gene Expression / Regulation
Answer: RNA (ribonucleic acid)
Figure 3.6 – Audesirk2 & Byers
3) RNA has base Uracil instead of Thymine (A U)
Types of RNA:
Messenger RNA (mRNA)
Carries code from DNA
to ribosomes
Ribosomal RNA (rRNA)
Combines with proteins
to form ribosomes
Transfer RNA (tRNA)
Carries appropriate amino
acids to ribosomesFigure 10.2 – Audesirk2 & Byers
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DNA RNA ProteinTranscription
Nucleus
Translation
Cytoplasm
Chapter 10: Gene Expression / Regulation
Central Dogma of Biology:
Figure 10.3 – Audesirk2 & Byers
S O S
Most organisms synthesize 20 unique amino acids
A T
G C= 4
AA TA CA GA
AT TT CT GT
AC TC CC GC
AG TG CG GG
= 16
How many possible three-base sequences (e.g., AAA) are there?
Chapter 10: Gene Expression / Regulation
The Genetic Code: The “Language” of Life
Answer: 64
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The genetic code is a triplet code:
• Three bases (called a codon) code for 1 amino acid
• More than 1 codon exists for most amino acids (see Table 10.3)
G C G A A G A G G G C A
Alanine Lysine Arginine Alanine
• Punctuation codons (start / stop) exist in genetic code
• Start = AUG
A U G
START
U A G
STOP
• Stop = UAG, UAA, UGA
Chapter 10: Gene Expression / Regulation
The Genetic Code: The “Language” of Life
DNA RNA ProteinTranscription
Nucleus
Translation
Cytoplasm
Chapter 10: Gene Expression / Regulation
Central Dogma of Biology:
Figure 10.3 – Audesirk2 & Byers
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Transcription (DNA RNA):
• RNA Polymerase binds to promoter region of gene
Step 1: Initiation
Promoter BodyTermination
Signal
GENET A C
• Different version of RNA polymerase synthesizes each RNA type
Transcription produces a single strand of RNA that is
complementary to one strand of DNA
Chapter 10: Gene Expression / Regulation
Non-coding region; protein binding sites
Step 2: Elongation
• RNA Polymerase “unwinds” DNA; synthesizes complementary copy
• Base pair rules apply except uracil replaces thymine
A T C G A A A T C G C G A G G T DNA
U A G C U U U A G C G C U C C A RNA
Chapter 10: Gene Expression / Regulation
Transcription:Initiation
Elongation
Figure 10.4 – Audesirk2 & Byers
Strand which is transcribed
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Transcription (DNA RNA):
• RNA Polymerase reaches termination signal
Step 3: Termination
Promoter BodyTermination
Signal
GENET A C
Transcription produces a single strand of RNA that is
complementary to one strand of DNA
Chapter 10: Gene Expression / Regulation
• RNA detaches from RNA Polymerase
• RNA Polymerase detaches from DNA
• DNA zips back up
Figure 10.4 – Audesirk2 & Byers
Transcription (DNA RNA):
Chapter 10: Gene Expression / Regulation
Multiple RNA polymerase can transcribe a single gene at the same time
Figure 10.5 – Audesirk2 & Byers
The transcription of genes into RNA is selective:
1) Only certain cells transcribe certain genes
• Insulin (hormone) Pancreas
2) Only one strand of DNA (template strand) is copied
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DNA RNA ProteinTranscription
Nucleus
Translation
Cytoplasm
Chapter 10: Gene Expression / Regulation
Central Dogma of Biology:
Figure 10.3 – Audesirk2 & Byers
Translation (RNA Protein):
Chapter 10: Gene Expression / Regulation
Step 1: mRNA processed in nucleus
• Exons = Coding segments
• Introns = Non-coding segments
Importance:
A) Multiple proteins from single gene
B) Quick / efficient protein evolution
Step 2: mRNA enters cytoplasm
• Exits nucleus via nuclear pores
Step 3: mRNA binds to ribosome (protein factories)
Composed of rRNA and proteins
• Composed of two (2) sub-units:
Small Sub-unit
Binds mRNA and part of tRNA
Large Sub-unit
Binds part of tRNA; contains catalytic site
Figure 10.2 / 10.7 – Audesirk2 & Byers
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Translation (RNA Protein):
Chapter 10: Gene Expression / Regulation
Step 4: tRNA delivers first amino acid to ribosome
• tRNA contains three bases (anticodon) that
form base pairs with mRNA codon
U A C Anticodon
MethionineAmino
Acid
• tRNA has correct amino acid attached for
the mRNA codon (61 unique tRNAs)
Large
Sub-unit
U A C
Met
Small Sub-unit
A U G A A G G C A U C U U A G
Translation (RNA Protein):
Chapter 10: Gene Expression / Regulation
Step 5: Elongation of protein
• The next tRNA with proper anticodon binds
to mRNA
Large
Sub-unit
U A C
Met
Small Sub-unit
A U G A A G G C A U C U U A GU U C
Lys
• Catalytic site joins amino acids together (peptide bond)
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Translation (RNA Protein):
Chapter 10: Gene Expression / Regulation
Step 5: Elongation of protein
• The next tRNA with proper anticodon binds
to mRNA
• Catalytic site joins amino acids together (peptide bond)
• 1st tRNA leaves and ribosome moves down one spot
Large
Sub-unitMet
Small Sub-unit
A U G A A G G C A U C U U A G
U U C
Lys
U A C
Translation (RNA Protein):
Chapter 10: Gene Expression / Regulation
Step 5: Elongation of protein
• The next tRNA with proper anticodon binds
to mRNA
• Catalytic site joins amino acids together (peptide bond)
• 1st tRNA leaves and ribosome moves down one spot
Large
Sub-unitMet
Small Sub-unit
A U G A A G G C A U C U U A G
U U C
Lys
U A C
• Cycle repeated
C G U
Ala
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Translation (RNA Protein):
Chapter 10: Gene Expression / Regulation
Step 6: Termination of protein
• Process continues until stop codon is reached
• Finished protein is released from ribosome
Small Sub-unit
A U G A A G G C A U C U U A G
Met Lys Ala
A G A
Ser
Translation (RNA Protein):
Chapter 10: Gene Expression / Regulation
Step 6: Termination of protein
• Process continues until stop codon is reached
• Finished protein is released from ribosome
Small Sub-unit
A U G A A G G C A U C U U A G
Met Lys Ala
A G A
Ser
• Sub-units of ribosome separate from mRNA
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Translation (RNA Protein):
Chapter 10: Gene Expression / Regulation
Step 6: Termination of protein
•• Process continues until stop codon is reached
• Finished protein is released from ribosome
Small Sub-unit
A U G A A G G C A U C U U A G
Met Lys Ala Ser
• Sub-units of ribosome separate from mRNA
Transcription / Translation Review:
Chapter 10: Gene Expression / RegulationFigure 10.9 – Audesirk2 & Byers
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Once Again - Mistakes Happen...
Types of Mutations:
1) Point Mutation: A pair of bases is incorrectly matched
Mutation:
Changes in the sequence of bases in DNA
A T A T A T
T A T C T A
Chapter 10: Gene Expression / Regulation
Possible outcomes of a point mutation (active gene):
1) Protein is unchanged (codes for same amino acid)
• CTC and CTT still code for leucine
2) New protein equivalent to original protein
• Replace hydrophobic AA with hydrophobic AA (neutral mutation)
3) Protein structure is changed (problem causing – e.g., sickle cell anemia)
4) Protein function destroyed due to stop codon insertion
• AAG codes of amino acid; ATG is a stop codon
Once Again - Mistakes Happen...
Types of Mutations:
Chapter 10: Gene Expression / Regulation
3) Deletion Mutation: One or more nucleotide pairs are deleted from
a gene
A T A A T
T A T T A ??
A T A T A TT A T C A T
GA
Mutation:
Changes in the sequence of bases in DNA
2) Insertion Mutation: One or more nucleotide pairs are inserted into
a gene
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Chapter 10: Gene Expression / Regulation
Once Again - Mistakes Happen...Mutation:
Changes in the sequence of bases in DNA
Chapter 10: Gene Expression / Regulation
Mutations provide the raw material for evolution...
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Regulation of Genes Occur Across Central Dogma:
1) Rate of transcription controlled:
A) Regulatory proteins
• Assist / block binding of RNA polymerase
B) Chromosome condensation (tightly packed areas)
• RNA polymerase can’t access regions
C) Chromosome inactivity (XX vs. XY chromosomes)
Chapter 10: Gene Expression / Regulation
Proper regulation of gene expression crucial for survival
For Example:
30,000 genes in human genome
• Individual cells express small fraction of genes
• Gene expression changes over time
• Some genes never exptressed
Barr Body: Inactive X chromosome in females
• Random during development for which X chromosome inactivates
Chapter 10: Gene Expression / Regulation
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Regulation of Genes Occur Across Central Dogma:
1) Rate of transcription controlled
Chapter 10: Gene Expression / Regulation
Proper regulation of gene expression crucial for survival
For Example:
30,000 genes in human genome
• Individual cells express small fraction of genes
• Gene expression changes over time
• Some genes never exptressed
2) Genes may produce different protein products
3) Rate of translation controlled (linked to mRNA stability)
4) Protein requires activation modifications
5) Life span of protein controlled
Gene Regulation:
Chapter 10: Gene Expression / RegulationFigure 10.11 – Audesirk2 & Byers