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Michael Cummings
Chapter 9
Gene Expression and Gene
Regulation
Part 1
David Reisman • University of South Carolina
9.1 The Link between Genes and Proteins
1902 Archibald Garrod published a paper on the
condition of alkaptonuria – he proposed that
abnormal phenotypes resulted from biochemical
defects or ―inborn errors of metabolism‖
1941 George Beadle and Edward Tatum firmly
established the link between genes, the proteins
produced from those genes, and a visible
phenotype (won the Nobel Prize in 1958)
9.3 Tracing the Flow of Genetic Information
Production of protein from instructions on the DNA
requires several steps
- Transcription = Production of mRNA
- Translation = Production of protein using mRNA,
tRNA, and rRNA
- Folding of the protein into the active 3-D form
DNA
Transcription
pre-mRNA
mRNA processing
Cell
Cytoplasm
Nucleus
mRNA
Translation
Polypeptide
Fig. 9-2, p. 201
Adenine (A)
Adenine (A)
Guanine (G)
Guanine (G)
Cytosine (C)
Cytosine (C)
Thymine
(T)
Uracil (U)
RNA
DNA
Fig. 8-7, p. 183
Nucleic Acids
DNA
1.
2.
3.
4.
5.
6.
Usually double-stranded
Thymine as a bas
Sugar is deoxyribose
Contains protein coding info
Does not act as an enzyme
Permanent
Table 10.2
RNA
1.
2.
3.
4.
5.
6.
Usually single-stranded
Uracil as a base
Sugar is ribose
Carries protein code info
Can function as an enzyme
Transient
Ribose
Ribose
There are three major types of RNA
- messenger RNA or mRNA
- ribosomal RNA or rRNA
- transfer RNA or tRNA
Ribose
Ribose
Fig. 8-11, p. 187
9.4 Transcription Produces
Genetic Messages
 Transcription begins when DNA unwinds and one
strand is used as template to make a pre-mRNA
molecule
 Initiation: Binding of transcription factors and RNA
polymerase to promoter region in the DNA
 Elongation: RNA polymerase adds nucleotides in
5’  3’ direction
 Termination: terminator sequence is reached
Gene region
5’ Promoter region
RNA polymerase, the enzyme that
catalyzes transcription
(a) RNA polymerase binds to a promoter in the DNA, along with
regulatory proteins (initiation). The binding positions the
polymerase near a gene in the DNA.
Only one strand of DNA provides a template for
transcription of mRNA.
Fig. 9-3a, p. 200
Newly forming
RNA transcript
DNA template
winding up
DNA template
unwinding
(b) The polymerase begins to move along the DNA and unwind it. As
it does, it links RNA nucleotides into a strand of RNA in the order
specified by the base sequence of the DNA (elongation).
The DNA double helix rewinds after the polymerase passes. The
structure of the “opened” DNA molecule at the transcription site is
called a transcription bubble, after its appearance.
Fig. 9-3b, p. 200
Pre-mRNA must Undergo Modification and
Splicing
 Transcription produces large mRNA precursor
molecules called pre-mRNA
 Before leaving nucleus – mRNA is processed
• 1. 5’ methyl cap added - Recognition site for protein synthesis
• 2. 3’ poly A tail - Stabilizes the mRNA
• 3. Removal of introns (intervening sequences- don’t code for
protein)
Unit of transcription in DNA strand
Exon
Intron
Exon
Intron
Exon
Transcription into pre-mRNA
Cap
Poly-A tail
Snipped out
Snipped out
Mature mRNA transcript
Fig. 9-4, p. 202
Alternative Splicing
Mutations in Splicing Sites and Genetic
Disorders
 Splicing defects cause several human genetic
disorders
 One hemoglobin disorder, b-thalassemia, is due to
mutations at the exon/intron region that results in
lower splicing efficiency and lower b-globin protein
DNA
Transcription
pre-mRNA
mRNA processing
Cell
Cytoplasm
Nucleus
mRNA
Translation
Polypeptide
Fig. 9-2, p. 201
9.5 Translation Requires the
Interaction of Several Components
 Translation requires the interaction of mRNA, amino
acids, ribosomes, tRNA molecules, and energy
sources
 mRNA is read in groups of 3 amino acids called
codons
Codon Chart—20 different amino acids to make all
the proteins in living organisms
Genetic Code
 Triplet code (3 mRNA bases = 1 amino acid)
 Redundant – more than one codon can specify an
amino acid
 Unambiguous – each codon codes for just one
amino acid
 Universal – nearly all organisms use the same
code - bacteria, plants, animals
INITIATION
(a) A mature mRNA
leaves the nucleus
and enters the
cytoplasm, which
has many free amino
acids, tRNAs, and
ribosomal subunits.
An initiator tRNA
carrying methionine
binds to a small
ribosomal subunit
and the mRNA.
mRNA
Initiator Small
tRNA
ribosomal
subunit
Large
ribosomal
subunit
Fig. 9-9a, p. 206
Transfer RNA (tRNA)
(b) A large ribosomal
subunit joins, and the
cluster is now called
an initiation complex.
Fig. 9-9b, p. 206
ELONGATION
A peptide bond
forms between the
first two amino acids
(here, methionine
and valine).
(c) An initiator tRNA carries the amino
acid methionine, so the first amino acid
of the new polypeptide chain will be
methionine. A second tRNA binds the
second codon of the mRNA (here, that
codon is GUG, so the tRNA that binds
carries the amino acid valine).
Fig. 9-9c, p. 207
A peptide bond
forms between the
second and third
amino acids (here
valine and leucine).
(d) The first tRNA is
released and the ribosome
moves to the next codon in
the mRNA. A third tRNA
binds to the third codon of
the mRNA (here, that codon
is UUA, so the tRNA carries
the amino acid leucine).
Fig. 9-9d, p. 207
A peptide bond forms
between the third and
fourth amino acids (here,
leucine and glycine).
(e) The second tRNA is released
and the ribosome moves to the
next codon. A fourth tRNA
binds the fourth mRNA codon
(here, that codon is GGG, so
the tRNA carries the amino acid
glycine).
Fig. 9-9e, p. 207
TERMINATION
(f) Steps d and e are repeated over and over until
the ribosome encounters a stop codon in the
mRNA. The mRNA transcript and the new
poypeptide chain are released from the ribosome.
The two ribosomal subunits separate from each
other. Translation is now complete. Either the
polypeptide chain will join the pool of proteins in
the cytoplasm, the nucleus, or will enter the rough
ER of the endomembrane system (Section 4.9).
Fig. 9-9f, p. 207
Polysomes
 Once a ribosome has
started translation, new
initiation complexes can
form on an mRNA in order
to produce many protein
molecules.
Template DNA:
3’TGTACGCGGTCAGCTTTATT5’
(red = introns)
Mature mRNA:
tRNA anticodons:
Amino acids:
27
Template DNA:
3’TGTACGCGGTCAGCTTTATT5’
(red = introns)
Mature mRNA: AUG AGU CGA UAA
tRNA anticodons:
Amino acids:
28
Template DNA:
3’TGTACGCGGTCAGCTTTATT5’
(red = introns)
Mature mRNA: AUG AGU CGA UAA
tRNA anticodons: UAC UCA GCU AUU
Amino acids:
29
**Mature mRNA: AUG AGU CGA UAA**
tRNA anticodons: UAC UCA GCU AUU
Amino acids:
Methionine,
Serine,
Arginine,
Stop
30
H
Amino
group
Carboxyl
group
R
(a)
Amino acid
Fig. 9-6a, p. 203
Each amino
acid has a
specific
R-group.
9.7 Polypeptides are Folded to Form
Proteins
 After synthesis, polypeptides fold into a threedimensional shape, often assisted by other proteins,
called chaperones
 Improper folding leads to incorrect protein structure
and inability to perform function (Alzheimer,
Huntington, Parkinson diseases)
 Four levels of protein structure are recognized
Four Levels of Protein Structure
 Primary structure (1O)
• The amino acid sequence in a polypeptide chain
 Secondary structure (2O)
• The pleated or helical structure in a protein molecule
resulting from the peptide bonds between amino
acids
Four Levels of Protein Structure
 Tertiary structure (3O)
• The folding of the helical and pleated sheet
structures due to interaction of the R-groups.
 Quaternary structure (4O)
• The interaction of two or more polypeptide chains to
form a functional protein
Levels of Protein Structure
1O
2O
3O
4O
Exploring Genetics:
Antibiotics and Protein Synthesis
 Antibiotics are produced by microorganisms as a
defense mechanism
 Many antibiotics affect one or more stages in
protein synthesis. For example:
• Tetracycline: initiation of transcription
• Streptomycin: codon-anticodon interaction
• Erythromycin: ribosome movement along mRNA
Other topics in Chp 9 Part 2
 Protein folding diseases
 Regulation of protein synthesis occurs at several
levels:
•
•
•
•
Timing of transcription
The rate of translation
The ways in which proteins are processed
The rate of protein break-down