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Chapter 12
Gene Expression and
Regulation
Lecture Outlines by Gregory Ahearn,
University of North Florida
Copyright © 2011 Pearson Education Inc.
Chapter 12 At a Glance
 12.1 How Is the Information in DNA Used in a
Cell?
 12.2 How Is the Information in a Gene
Transcribed into RNA?
 12.3 How Is the Base Sequence of Messenger
RNA Translated into Protein?
 12.4 How Do Mutations Affect Protein Function?
 12.5 How Are Genes Regulated?
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12.1 How Is the Information in DNA Used in a Cell?
 The link between DNA and protein
– DNA contains the “molecular blueprint” of every
cell
– Proteins are the construction workers of the cell
– Proteins control cell shape, function,
reproduction, and synthesis of biomolecules
– Therefore, there must be a flow of information
from DNA to protein
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12.1 How Is the Information in DNA Used in a Cell?
 Most genes contain the information for the
synthesis of a single protein
– Experiments on bread molds in the 1940s
showed that one gene codes for one protein
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12.1 How Is the Information in DNA Used in a Cell?
 DNA provides instructions for protein synthesis
via RNA intermediaries
– DNA in eukaryotes is kept in the nucleus
– Protein synthesis occurs at ribosomes in the
cytoplasm
– DNA information must be carried by an
intermediary, ribonucleic acid (RNA), from the
nucleus to the cytoplasm
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12.1 How Is the Information in DNA Used in a Cell?
 DNA provides instructions for protein synthesis
via RNA intermediaries (continued)
– RNA differs structurally from DNA in three ways
–RNA is usually single-stranded
–RNA has the sugar ribose rather than
deoxyribose in its backbone
–RNA contains the nitrogenous base uracil (U)
instead of thymine (T)
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Table 12-1
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12.1 How Is the Information in DNA Used in a Cell?
 DNA provides instructions for protein synthesis
via RNA intermediaries (continued)
– There are three types of RNA involved in protein
synthesis
–Messenger RNA (mRNA) carries DNA gene
information to the ribosome
–Transfer RNA (tRNA) brings amino acids to
the ribosome
–Ribosomal RNA (rRNA) is part of the
structure of ribosomes
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12.1 How Is the Information in DNA Used in a Cell?
 DNA provides instructions for protein synthesis via RNA
intermediaries (continued)
– RNA occurs in many other roles besides protein
synthesis
– RNA is used as the genetic material in some viruses,
such as HIV
– Enzymatic RNA, called ribozymes, catalyzes various
reactions, including the cutting apart of other
molecules of RNA
– Xist RNA prevents the genetic information in one of
the X chromosomes of female mammals from being
used
– MicroRNA may play a role in regulating development
and fighting disease
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Cells Synthesize Three Major Types of RNA That
Are Required for Protein Synthesis
codons
A U G U G C G A G U U A
(a) Messenger RNA (mRNA)
The base sequence of mRNA carries
the information for the amino acid
sequence of a protein; groups of
these bases, called codons, specify
the amino acids
catalytic site
large
subunit
1
2
tRNA/amino acid
binding sites
small
subunit
rRNA combines with proteins to form
ribosomes; the small subunit binds mRNA;
the large subunit binds tRNA and
catalyzes peptide bond formation between
amino acids during protein synthesis
(b) Ribosome: contains ribosomal RNA (rRNA)
tyr
attached
amino acid
tRNA
anticodon
(c) Transfer RNA (tRNA)
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Each tRNA carries a specific amino acid (in
this example, tyrosine [tyr]) to a ribosome
during protein synthesis; the anticodon of
tRNA pairs with a codon of mRNA,
ensuring that the correct amino acid is
incorporated into the protein
Fig. 12-1
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12.1 How Is the Information in DNA Used in a Cell?
 DNA provides instructions for protein synthesis via RNA
intermediaries (continued)
– Messenger RNA carries the code for protein synthesis
from DNA to the ribosomes
– Ribosomal rRNA and proteins form ribosomes
– Ribosomes, the structures that carry out translation,
are composed of rRNA and many different proteins
– Each ribosome consists of two subunits—one small
and one large—that contain various binding and
catalytic sites needed for protein synthesis
– Transfer tRNA carries amino acids to the ribosomes for
addition to the growing protein
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12.1 How Is the Information in DNA Used in a Cell?
 Overview: Genetic information is transcribed
into RNA and then translated into protein
– DNA directs protein synthesis in a two-step
process
1. Information in a DNA gene is copied into RNA
in the process of transcription
2. Messenger RNA, together with tRNA, amino
acids, and a ribosome, synthesizes a protein
in the process of translation of the genetic
information contained in the mRNA
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Genetic Information Flows from DNA to RNA to
Protein
gene
DNA
(nucleus)
(cytoplasm)
Transcription of the
gene produces an
(a) Transcription
mRNA with a
nucleotide sequence
complementary to one
messenger RNA of the DNA strands
Translation of the mRNA
produces a protein molecule
with an amino acid sequence
determined by the nucleotide
sequence in the mRNA
(b) Translation
ribosome
protein
Fig. 12-2
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Table 12-2
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12.1 How Is the Information in DNA Used in a Cell?
 The genetic code uses three bases to specify an amino
acid
– The genetic code translates the sequence of bases in
nucleic acids into the sequence of amino acids in
proteins
– Given that there are 20 amino acids but only four bases,
statistically, the smallest number of bases that could
combine to yield a different sequence for each of the 20
amino acids is three
– A two-base code could produce only 16 combinations
– The three-base code has the potential to create 64
combinations
– Bases in mRNA are read by the ribosome in triplets
called codons
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12.1 How Is the Information in DNA Used in a Cell?
 The genetic code uses three bases to specify an amino
acid (continued)
– Marshall Nirenberg and Heinrich Matthaei cracked the
genetic code by creating artificial mRNAs of known
sequence and observing what proteins they produced
– For example, an mRNA strand composed entirely of
uracil (UUUUUUUU…) produced a protein consisting
entirely of the amino acid phenylalanine
– Therefore, they concluded that the triplet UUU is the
codon for phenylalanine
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12.1 How Is the Information in DNA Used in a Cell?
 The genetic code uses three bases to specify an amino
acid (continued)
– The genetic code is usually written in terms of the base
triplets in mRNA (rather than in DNA)
– Each codon specifies a unique amino acid in the genetic
code
– Each mRNA also has a start codon (AUG) and one of
three stop codons (UAG, UAA, and UGA)
– Each codon species only one specific amino acid;
however, some amino acids are specified by as many as
six different codons
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Table 12-3
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12.1 How Is the Information in DNA Used in a Cell?
 The genetic code uses three bases to specify
an amino acid (continued)
– Decoding the codons of mRNA is the job of tRNA
and ribosomes
–Each unique tRNA has three exposed bases,
called an anticodon, which are
complementary to codon bases in mRNA
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12.2 How Is the Information in a Gene Transcribed
into RNA?
 Overview of transcription
– Transcription of a DNA gene into RNA has three
stages
1. Initiation
2. Elongation
3. Termination
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12.2 How Is the Information in a Gene Transcribed
into RNA?
 Overview of transcription (continued)
– The three steps of transcription correspond to
the three major parts of most genes
–A promoter region at the beginning of the gene
marks where transcription is to be initiated
–The “body” of the gene corresponds with
where elongation of the RNA strand occurs
–A termination signal at the end of the gene
marks where RNA synthesis is to terminate
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12.2 How Is the Information in a Gene Transcribed
into RNA?
 Transcription begins when RNA polymerase binds to
the promoter of a gene
– The enzyme RNA polymerase synthesizes RNA
– RNA polymerase binds to the promoter region at the
beginning of a gene
– The promoter consists of (1) a site that binds RNA
polymerase and (2) one or more regulatory sequences
that enhance or suppress transcription of the gene
– When RNA polymerase binds to the promoter, the DNA
molecule is unwound and strands are separated at the
beginning of the gene sequence
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Initiation
DNA
gene 1
gene 2
gene 3
RNA
polymerase
DNA
direction of
transcription
promoter
beginning of
gene (3´ end)
1 Initiation: RNA polymerase binds to the promoter region of DNA near the beginning
of a gene, separating the double helix near the promoter.
Fig. 12-3 (1 of 4)
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12.2 How Is the Information in a Gene Transcribed
into RNA?
 Elongation generates a growing strand of RNA
– RNA polymerase synthesizes a sequence of RNA
nucleotides along one of the DNA strands, the template
strand
– RNA polymerase travels along the DNA template strand
starting at the 3 end of a gene and moving toward the 5
end
– The bases in the newly synthesized RNA strand are
complementary to the DNA template strand
– Starting at the initiation end, the forming RNA strand
drifts away from the DNA template strand, while RNA
polymerase holds the forming end to the template
– As the RNA strand leaves the DNA strands, the helix
re-forms
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Elongation
RNA
DNA template strand
2 Elongation: RNA polymerase travels along the DNA template strand (blue),
unwinding the DNA double helix and synthesizing RNA by catalyzing the addition of ribose
nucleotides into an RNA molecule (red). The nucleotides in the RNA are complementary to
the template strand of the DNA.
Fig. 12-3 (2 of 4)
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12.2 How Is the Information in a Gene Transcribed
into RNA?
 Transcription stops when RNA polymerase
reaches the termination signal
– RNA polymerase reaches a termination
sequence, releases the completed RNA strand,
and detaches from the DNA
– The RNA polymerase is then free to bind to the
promoter region of another gene and to
synthesize another RNA molecule
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Author Animation: Transcription
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Termination and Conclusion of Transcription
termination signal
3 Termination: At the end of the gene, RNA polymerase encounters a DNA sequence
called a termination signal. RNA polymerase detaches from the DNA and releases the
RNA molecule.
DNA
RNA
4 Conclusion of transcription: After termination, the DNA completely rewinds into a
double helix. The RNA molecule is free to move from the nucleus to the cytoplasm for
translation, and RNA polymerase may move to another gene and begin transcription once
again.
Fig. 12-3 (3 & 4 of 4)
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RNA Transcription in Action
gene
growing
end of
RNA
gene
molecules
DNA
beginning
of gene
Fig. 12-4
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Messenger RNA synthesis differs between
prokaryotes and eukaryotes
– Messenger RNA synthesis in prokaryotes
–All the nucleotides in a gene encode for the
amino acids of a protein; there are no
sequences that are not transcribed into RNA
–Genes for related functions are adjacent and
are transcribed together
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Messenger RNA synthesis in prokaryotes
(continued)
–Because prokaryotes have no nuclear
membrane, translation and transcription are
not separated in space or time
–Ribosomes begin translation at the free 5 end
of mRNA, even as RNA polymerase is
elongating the mRNA at its 3 end
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Messenger RNA Synthesis in Prokaryotic Cells
gene regulating
DNA sequences
gene 1
gene 2
gene 3
genes coding enzymes in a
single metabolic pathway
(a) Gene organization on a prokaryotic chromosome
DNA
mRNA
ribosome
direction of transcription
RNA
polymerase
DNA
mRNA
protein
ribosome
(b) Simultaneous transcription and translation in prokaryotes
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Fig. 12-5
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Messenger RNA synthesis in eukaryotes
– In eukaryotes, the DNA is in the nucleus and the
ribosomes are in the cytoplasm
– The genes that encode the proteins for a
metabolic pathway are not clustered together on
the same chromosome
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Messenger RNA synthesis in eukaryotes
(continued)
– Each gene consists of two or more segments of
DNA that encode for protein, called exons, that
are interrupted by other segments that are not
translated, called introns
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Messenger RNA synthesis in eukaryotes (continued)
– Transcription of a gene produces a very long RNA strand
that contains introns and exons
– This long strand, which extends beyond the first and
last exons, is often called precursor mRNA, or premRNA
– More nucleotides are added at the beginning and end of
the pre-mRNA molecule, forming a “cap” and “tail”
– The nucleotides assist with moving the RNA through
the nuclear envelope, to bind the mRNA to a
ribosome, and to prevent cellular enzymes from
breaking down the mRNA
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Messenger RNA synthesis in eukaryotes
(continued)
– Enzymes in the nucleus cut out the introns and
splice together the exons to make true mRNA
– The mRNA then exits the nucleus through a
membrane pore and associates with a ribosome
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Messenger RNA Synthesis in Eukaryotic Cells
exons
DNA
promoter
introns
(a) Eukaryotic gene structure
DNA
1 Transcription
pre-mRNA
2 An RNA cap and tail are added
cap
tail
3 RNA splicing
finished mRNA
4 Finished mRNA is moved
to the cytoplasm for translation
(b) RNA synthesis and processing in eukaryotes
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introns
are cut
out and
broken
down
Fig. 12-6
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Possible functions of intron-exon gene structure
– Through alternative splicing of the exons in a
gene, a cell can make multiple proteins from a
single gene
–Alternative splicing represents an exception to
Beadle and Tatum’s one gene–one protein
relationship
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Possible functions of intron-exon gene structure
(continued)
– A second function for the presence of intronexon gene structure is that fragmented genes
may provide a quick and efficient way for
eukaryotes to evolve new proteins with new
functions
–If breaks in chromosomes occur in introns,
exons may remain intact and be spliced to
other chromosomes in ways that produce new,
useful proteins
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 During translation, mRNA, tRNA, and ribosomes
cooperate to synthesize proteins
– Like transcription, translation has three steps
1. Initiation
2. Elongation
3. Termination
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Step 1: Initiation
1. A preinitiation complex forms, consisting of the
small ribosomal subunit, a methionine tRNA, and
several other proteins
2. The UAC anticodon of the methionine tRNA in
the preinitiation complex binds the mRNA
molecule by base-pairing with the AUG start
codon at the beginning (5 end) of the mRNA
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Step 1: Initiation (continued)
3. The large ribosomal subunit attaches to the
small subunit, holding the mRNA between the
two subunits and holding the methionine tRNA in
its first tRNA binding site
– The ribosome is fully assembled at this point
and ready to begin translation
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Translation Is the Process of Protein Synthesis:
Initiation
Initiation:
amino acid
met
tRNA
preinitiation
complex
catalytic site
met
anticodon
methionine
tRNA
U A C
small
ribosomal
subunit
second tRNA binding site
U A C
mRNA
GC A U GGU U C A
first
tRNA
binding
site
large
ribosomal
subunit
U AC
GC A UGGU UCA
start codon
1 A tRNA with an attached
methionine amino acid binds
to a small ribosomal subunit,
forming a preinitiation complex.
2 The preinitiation complex binds
to an mRNA molecule. The
methionine (met) tRNA anticodon
(UAC) base-pairs with the start
codon (AUG) of the mRNA.
3 The large ribosomal subunit binds
to the small subunit. The methionine
tRNA binds to the first tRNA site on
the large subunit.
Fig. 12-7 (1-3 of 9)
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Step 2: Elongation
4. A second tRNA anticodon base-pairs with the
second codon on the mRNA, as the tRNA is
bound to the second tRNA binding site
5. The catalytic site of the large subunit breaks the
bond holding methionine to its tRNA and forms a
peptide bond between this amino acid and the
amino acid attached to the second tRNA
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Step 2: Elongation (continued)
6.The “empty” tRNA is released and the ribosome
moves down the mRNA one codon
– The tRNA with the growing amino acid chain
is now in the ribosome’s first binding site, and
the second binding site is empty, awaiting
another tRNA
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Step 2: Elongation (continued)
7. A third tRNA, with an anticodon complementary
to the third codon of the mRNA, enters the
empty second binding site of the ribosome and
base-pairs with the mRNA
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Step 2: Elongation (continued)
8. The catalytic site on the large subunit now
passes the growing protein chain onto the third
amino acid, the empty tRNA leaves the
ribosome, and the ribosome shifts to the next
codon on the mRNA
– This process continues, one codon at a time,
until a stop codon is reached
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Step 3: Termination
9. When the ribosome reaches a stop codon in the
mRNA molecule, releasing factors cause it to
release the completed peptide chain and the
mRNA and to disassemble into its large and
small subunits
– A tRNA does not bind the stop codon
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Author Animation: Translation
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Translation Is the Process of Protein Synthesis:
Elongation and Termination
Elongation:
catalytic
site
peptide
bond
U A C C A A
U A C C A A
G C A U G G U U C A
G C A U G G U U C A
initiator tRNA
detaches
C
A A
G C A U G G U U C A U A G
ribosome moves one codon to the right
4 The second codon of mRNA
(GUU) base-pairs with the
anticodon (CAA) of a second
tRNA carrying the amino acid
valine (val). This tRNA binds to
the second tRNA site on the large
subunit.
5 The catalytic site on the large
subunit catalyzes the formation
of a peptide bond linking the
amino acids methionine and
valine. The two amino acids are
now attached to the tRNA in
the second binding site.
6 The "empty" tRNA is released and the
ribosome moves down the mRNA, one
codon to the right. The tRNA that is
attached to the two amino acids is now in
the first tRNA binding site and the second
tRNA binding site is empty.
Fig. 12-7 (4-6 of 9)
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Translation Is the Process of Protein Synthesis:
Elongation and Termination
Termination:
C A A G U A
C A A G U A
completed
peptide
stop codon
G C A U G G U U C A U A G
C A U G G U U C A U A G
CGAA UC UAGUAA
7 The third codon of mRNA
(CAU) base-pairs with the
anticodon (GUA) of a tRNA
carrying the amino acid
histidine (his). This tRNA enters
the second tRNA binding site
on the large subunit.
8 The catalytic site forms a
peptide bond between valine and
histidine, leaving the peptide
attached to the tRNA in the
second binding site. The tRNA in
the first site leaves, and the
ribosome moves one codon over
on the mRNA.
9 This process repeats until a
stop codon is reached; the
mRNA and the completed
peptide are released from the
ribosome, and the subunits
separate.
Fig. 12-7 (7-9 of 9)
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Summing up
– Each DNA gene codes for a single protein
– Transcription produces an mRNA strand
complementary to the DNA gene template strand
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Summing up (continued)
– The mRNA strand leaves the nucleus and
associates with a ribosome in the cytoplasm
– Transfer RNAs in the cytoplasm are loaded with
their appropriate amino acids by cytoplasmic
enzymes
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12.3 How Is the Base Sequence of Messenger RNA
Translated into Protein?
 Summing up (continued)
– The ribosome “selects” the tRNAs on the basis of
the base-pairing of the anticodon with the
exposed mRNA codon
– The mRNA contains a stop codon to define
where protein synthesis ends
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Complementary Base-Pairing Is Critical to the
Process of Decoding Genetic Information
gene
(a) DNA
A T G G G A G T T
complementary
DNA strand
template DNA
strand
etc.
T A C C C T C A A etc.
codons
A U G G G A G U U
etc.
(b) mRNA
anticodons
(c) tRNA
U A C
C C U
C A A etc.
amino acids
(d) protein
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methionine glycine
valine
etc.
Fig. 12-8
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12.4 How Do Mutations Affect Protein Function?
 Mutations are changes in the base sequence of DNA
caused by mistakes during replication or by various
environmental factors
 Mutations take many forms and can affect protein
function in many ways
– Mutations fall into five categories
– Inversions
– Translocations
– Deletions
– Insertions
– Substitutions
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12.4 How Do Mutations Affect Protein Function?
 Mutations take many forms and can affect protein
function in many ways (continued)
– Inversions and translocations occur when pieces of
DNA are broken apart and reattached, within a single
chromosome or to a different chromosome
– These mutations may be relatively benign if entire genes
are merely moved from one place to another
– However, if a gene is split in two, it will no longer code for
a complete, functional protein
– Severe hemophilia is often caused by an inversion in
the gene that encodes a protein required for blood
clotting
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12.4 How Do Mutations Affect Protein Function?
 Mutations take many forms and can affect
protein function in many ways (continued)
– A deletion occurs when one or more nucleotides
are removed from the gene sequence
– An insertion occurs when one or more
nucleotides are added to the gene sequence
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12.4 How Do Mutations Affect Protein Function?
 Deletions and insertions (continued)
– Depending on how many nucleotides are
involved, deletions and insertions can cause a
misreading of a gene’s codons during
transcription or replication
–The codons in THEDOGSAWTHECAT is
changed by deletion of the letter “E” to THD
OGS AWT HEC AT
–Such mutations are called frameshift
mutations
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12.4 How Do Mutations Affect Protein Function?
 Deletions and insertions (continued)
– Proteins that result from deletions and insertions
have a very different amino acid sequence and
almost always are nonfunctional
– Deletions and insertions of three nucleotides (or
a multiple of three) do not cause a shift of the
reading frame and, so, may simply subtract or
add a harmless amino acid to the protein
– The defective myostatin gene of Belgian Blue
cattle has an 11-nucleotide deletion, generating
a premature stop codon
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12.4 How Do Mutations Affect Protein Function?
 Mutations take many forms and can affect protein
function in many ways (continued)
– When a nucleotide substitution (point mutation)
occurs, an incorrect nucleotide takes the place of a
correct one
– A point mutation sometimes does not change the amino
acid sequence of the protein
– Because many amino acids are encoded by more
than one codon, the mutation may cause the same
amino acid to be added
– A known point mutation in the beta-globin gene for
hemoglobin causes CTC to change to CTT, but since
both codons code for glutamic acid, the protein is
unchanged
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12.4 How Do Mutations Affect Protein Function?
 With some nucleotide substitutions, the substituted
amino acid may be functionally equivalent to the normal
one, allowing the mutated protein to function normally
– In beta-globin, the amino acids on the outside of the
protein must be hydrophilic to keep the protein dissolved
in the cytoplasm of red blood cells, but which hydrophilic
amino acids are on the outside doesn’t matter much
– In beta-globin, a point mutation of the CTC codon to GTC
causes glutamic acid (hydrophilic) to be replaced with
glutamine (also hydrophilic), but the resulting protein
functions well
– Substitutions causing no amino acid changes or changes
that are unimportant to function are called neutral
mutations
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12.4 How Do Mutations Affect Protein Function?
 Some substitutions cause an altered amino acid
sequence that change protein function
dramatically, usually for the worse
–The substitution of an adenine for a thymine in
the CTC  CAC mutation in a hemoglobin
gene causes valine (hydrophobic) to replace
glutamic acid (hydrophilic)
–Placing this hydrophobic amino acid on the
outside of the hemoglobin molecule leads to
the clumping of hemoglobin and distortion of
the red blood cell seen in sickle cell anemia
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12.4 How Do Mutations Affect Protein Function?
 When a nucleotide substitution (point mutation) occurs,
an incorrect nucleotide takes the place of a correct one
(continued)
– The point mutation may introduce a premature stop
codon, leading to an mRNA that produces an incomplete
protein
– Such a mutation in the beta-globin gene prevents
production of functional beta-globin protein
– This leads to beta-thalassemia
– People with this mutation have only alpha-globin
subunits and require frequent blood transfusions to
survive
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Table 12-4
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12.4 How Do Mutations Affect Protein Function?
 Mutations provide the raw material for evolution
– Mutations are heritable changes in the DNA
– Approx. 1 in 105–106 eggs or sperm carry a
mutation
– Most mutations are harmful or neutral
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12.4 How Do Mutations Affect Protein Function?
 Mutations provide the raw material for evolution
(continued)
– Mutations create new gene sequences and are
the ultimate source of genetic variation
– Mutant gene sequences that are beneficial may
spread through a population and become
common
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12.5 How Are Genes Regulated?
 The human genome contains 20,000 to 25,000
genes
 A given cell “expresses” (transcribes) only a
small number of genes
 Some genes are expressed in all cells, such as
genes coding for tRNAs, since all cells require
proteins
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12.5 How Are Genes Regulated?
 Other genes are expressed only in certain types
of cells, at certain times in an organism’s life, or
under specific environmental conditions
–For example, even though every cell in your
body contains the gene for casein, the major
protein in milk, this gene is expressed only in
certain cells in the breast, only in mature
women, and only when a woman is breastfeeding
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12.5 How Are Genes Regulated?

Regulation of gene expression may occur at three
different levels
1. At the level of transcription, regulation determines which
genes in a cell are expressed
2. At the level of translation, regulation determines how
much protein is made from a particular type of mRNA
3. At the level of protein activity, regulation determines
how long the protein lasts in a cell and how rapidly
protein enzymes catalyze specific reactions

Although these general principles apply to both
prokaryotic and eukaryotic organisms, there are some
differences as well
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12.5 How Are Genes Regulated?
 Gene regulation in prokaryotes
– Prokaryotic DNA is organized into units called
operons, which contain functionally related
genes
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12.5 How Are Genes Regulated?
 Gene regulation in prokaryotes (continued)
– Each operon consists of four parts
– A regulatory gene controls the timing and
rate of transcription of the other genes
– A promoter is the site that RNA polymerase
recognizes as the place to start transcription
– An operator governs the access of RNA
polymerase to the promoter
– The structural genes actually encode the
related enzymes or other proteins
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12.5 How Are Genes Regulated?
 Gene regulation in prokaryotes (continued)
– Whole operons are regulated as units, so that
functionally related proteins are synthesized
simultaneously when the need arises
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12.5 How Are Genes Regulated?
 Gene regulation in prokaryotes (continued)
– The intestinal bacterium Escherichia coli (E. coli)
lives on what its host eats
– Specific enzymes are needed to metabolize the
type of food that comes along
– For example, in newborn mammals, E. coli are
bathed in milk, which contains the milk sugar
lactose
– The lactose operon contains three structural
genes, each coding for an enzyme that aids in
lactose metabolism
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12.5 How Are Genes Regulated?
 Gene regulation in prokaryotes (continued)
– In the absence of lactose, the lactose operon is normally
shut off, or repressed, by a repressor protein
– The regulatory gene of the lactose operon directs the
synthesis of this protein, which represses the operon by
binding to the operator site
– Under these circumstances, RNA polymerase, although
able to find to the promoter, cannot get past the
repressor protein to transcribe the structural genes
– Consequently, lactose-metabolizing enzymes are not
synthesized
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12.5 How Are Genes Regulated?
 Gene regulation in prokaryotes (continued)
– When lactose is present, it binds the repressor and
changes the repressor’s shape
– When bound to lactose, the repressor’s altered shape
does not permit it to bind the operator
– Without the repressor in the operator, RNA polymerase is
able to reach the promoter and begin transcription of the
genes needed to metabolize lactose
– When lactose is no longer present, the repressor
resumes its inhibitory conformation and binds the
operator, thus blocking transcription again
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Regulation of the Lactose Operon
regulatory gene:
codes for
repressor protein
R
P
operator: repressor
protein binds here
O
gene 1
gene 2
gene 3
structural genes that code for
promoter: RNA
enzymes of lactose metabolism
polymerase
binds here
(a) Structure of the lactose operon
RNA
polymerase
transcription blocked
R
P
gene 1
gene 2
gene 3
a repressor protein
bound to the operator
site overlaps the promoter
free repressor
proteins
(b) Lactose absent
RNA polymerase binds to the
promoter and transcribes
the structural genes
R
O
gene 1
lactose bound to
repressor proteins
(c) Lactose present
Biology: Life on Earth, 9e
gene 2
gene 3
lactose-metabolizing
enzymes are synthesized
Fig. 12-9
Copyright © 2011 Pearson Education Inc.
12.5 How Are Genes Regulated?
 Gene regulation in eukaryotes
– Although eukaryotic gene regulation bears some
similarity to regulation in prokaryotes, the complexity of
eukaryotic cells leads to differences as well
– DNA is in a membrane-bound nucleus
– There are a variety of cell types in multicellular
eukaryotes
– The genome of eukaryotes is organized differently
– RNA transcripts undergo complex processing not seen
in prokaryotes
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12.5 How Are Genes Regulated?
 Gene regulation in eukaryotes (continued)
– Expression of genetic information by a
eukaryotic cell is a multistep process, beginning
with transcription of DNA and ending with a
protein that performs a particular function
– Regulation can occur at any of these steps
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12.5 How Are Genes Regulated?
 Gene expression in eukaryotes can be
regulated at a number of points
1.Cells can control the frequency at which an
individual gene is transcribed
2.The same gene may be used to produce
different mRNAs and protein products
– Differential splicing of exons yields different
proteins, according to a cell’s needs
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12.5 How Are Genes Regulated?
 Gene expression in eukaryotes can be
regulated at a number of points (continued)
3.Cells may control the stability and translation of
messenger RNAs
– Some mRNAs are long-lasting and translated
into protein many times; others are translated
only a few times before being degraded
– Small “regulatory RNA” molecules may block
translation of some mRNAs, or may even
target some mRNAs for destruction
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12.5 How Are Genes Regulated?
 Gene expression in eukaryotes can be regulated at a
number of points (continued)
4. Proteins may require modification before they can carry
out their functions
– Some modifications of the inactive enzyme involve
excising a segment of it, thus exposing the active site
and activating the enzyme
– Another common method of changing an enzyme’s
activity is phosphorylating or dephosphorylating it
– Controlling these modifications provides a way to
regulate the enzymes
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12.5 How Are Genes Regulated?
 Gene expression in eukaryotes can be
regulated at a number of points (continued)
5.Cells can control the rate at which proteins are
degraded
– By preventing or promoting a protein’s
degradation, a cell can rapidly adjust the
amount of a particular protein it contains
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An Overview of Information Flow in a Eukaryotic
Cell
DNA
1 Transcription
rRNA
 proteins
(nucleus)
pre-mRNA
Cells can control
the frequency of
transcription
tRNA
2 mRNA
processing
Different mRNAs
may be produced
from a single gene
mRNA
(cytoplasm)
ribosomes
mRNA
tRNA
amino acids
3 Translation
If the active protein
is an enzyme, it will
catalyze a chemical
reaction in the cell
inactive
protein
Cells can control the
stability and rate of
translation of
particular mRNAs
Modification
Cells can regulate
a protein’s activity
by modifying it
5 Degradation
Cells can regulate
a protein’s activity
by degrading it
4
substrate
active
protein
product
amino
acids
Fig. 12-10
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12.5 How Are Genes Regulated?
 In eukaryotic cells, transcriptional regulation
occurs on at least three levels
– The individual gene
– Regions of chromosomes
– Entire chromosomes
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12.5 How Are Genes Regulated?
 In eukaryotic cells, transcriptional regulation
occurs on at least three levels (continued)
– Because most gene promoters contain
transcription factor binding sites, or response
elements, transcription can be regulated by the
presence of transcription factors
–Free radicals cause the production of a
transcription factor that binds a free radical
response element in the promoter of a gene
that degrades free radicals
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12.5 How Are Genes Regulated?
 Because most gene promoters contain transcription
factor binding sites, or response elements, transcription
can be regulated by the activity of transcription factors
(continued)
– When egg production needs to be increased in birds,
the ovaries release estrogen
– The estrogen forms a complex with (and thus
activates) a transcription factor called estrogen
receptor
– The complex then binds the estrogen response
element in the albumin gene, making it easier for RNA
polymerase to bind to the promoter and initiate
transcription of mRNA
– The mRNA is then translated into large amounts of
albumin
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12.5 How Are Genes Regulated?
 In eukaryotic cells, transcriptional regulation
occurs on at least three levels (continued)
– Condensed or tightly wound regions of DNA can
make genes inaccessible to RNA polymerase
–Some condensed portions of chromosomes
contain structural elements of the
chromosome, but no genes
–Other condensed areas contain genes that the
cell may not currently need and will
decondense when the genes are needed
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12.5 How Are Genes Regulated?
 In eukaryotic cells, transcriptional regulation occurs on
at least three levels (continued)
– Large parts of chromosomes may be inactivated,
preventing transcription
– In female mammals, one entire X chromosome is
condensed
– In 1961, the geneticist Mary Lyon hypothesized that
one of the two X chromosomes in females was
inactivated in some way, so that its genes were not
expressed
– These so-called Barr bodies were discovered by
Murray Barr
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A Barr Body
Fig. 12-11
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12.5 How Are Genes Regulated?
 In female mammals, one entire X chromosome
is condensed (continued)
– We now know that about 85% of the genes on an
inactivated X chromosome are not transcribed
– Early in development (about the 16th day in
humans), one X chromosome in each of a
female’s cells begins to produce large amounts
of a regulatory RNA molecule called Xist
–Xist coats most of the chromosome,
condenses it into a tight mass, and prevents
transcription
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12.5 How Are Genes Regulated?
 In female mammals, one entire X chromosome
is condensed (continued)
– Because Barr bodies are formed early in
development, female mammals have large
clusters of cells with one X chromosome
inactivated and other clusters of cells in which
the other X chromosome is inactivated
–Each cluster is descended from a single cell of
the very early embryo
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12.5 How Are Genes Regulated?
 In female mammals, one entire X chromosome is
condensed (continued)
– This effect can be observed in the fur patterns of calico
cats
– The X chromosome of a cat contains a gene for fur
pigmentation
– Different patches of skin cells in a cat inactivate
different X chromosomes
– If there are two alleles for fur color in the cat’s
genotype, the cat will produce patches of different fur
color (usually orange and black), depending on which
X chromosome was condensed in the progenitor cell
that gave rise to each patch of cells
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Inactivation of the X Chromosome Regulates Gene
Expression
Fig. 12-12
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