818 Chapter 22 Nucleic Acids

Example 22-6
Relating Protein Amino Acid Sequence to the Directionality of an mRNA Segment
The structure of an mRNA segment obtained from a DNA template strand is
mRNA 39 AUU – CCG – UAC – GAC 59
What polypeptide amino acid sequence will be synthesized using this mRNA?
Solution
The directionality of an mRNA segment obtained from template DNA is 3′-to-5′
because the two segments must be antiparallel to each other (Section 22-5). The codons
in an mRNA must be read in the 5′-to-3′ direction to correctly use genetic code rela-
tionships to determine the sequence of amino acids in the peptide. Rewriting the given
mRNA with reversed directionality (5′-to-3′ direction) gives
mRNA 59 CAG – CAU – GCC – UUA 39
Note that in reversing the directionality from 3′-to-5′ to 5′-to-3′, the sequence of bases
in a codon is also reversed; for example, GAC becomes CAG.
Using the genetic code relationships between codon and amino acid (Table 22-2)
shows that this mRNA codon sequence codes for the amino acid sequence
N-end Gln!His!Ala!Leu C-end
Codons written from the 5′-to-3′ end in an mRNA give amino acids that corre-
spond to a peptide written from the N-terminal end to the C-terminal end.

Section 22-10 Quick Quiz

1. Which of the following statements concerning codons is incorrect ?
a. They are found within mRNA molecules.
b. They specify base sequence in terms of four-nucleotide units.
c. There are 64 of them.
d. no correct response
2. The genetic code is a listing that gives relationships between codons and
a. synonyms
b. genes
c. mRNAs
d. no correct response
3. Which of the following statements concerning the functions for codons is incorrect ?
a. Each standard amino acid is designated by a single codon.
b. Some standard amino acids are designated by more than one codon.
c. Some codons have a “stop” function rather than an “amino acid” function.
d. no correct response
4. Without reference to the genetic code, which of the following is definitely an incorrect
codon–amino acid pairing?
a. UUU–UUC and Phe–Phe
b. ACU–AAU and Thr–Asn
c. GCC–GCC and Ala–Gly
d. no correct response

Answers: 1. b; 2. d; 3. a; 4. c

22-11 Anticodons and tRNA Molecules

L e a r n i n g F oc u s
Be familiar with the relationships between (1) anticodons and tRNAs and (2) anticodons
and codons.

The amino acids used in protein synthesis do not directly interact with the codons of
an mRNA molecule. Instead, tRNA molecules function as intermediaries that deliver
amino acids to the mRNA. At least one type of tRNA molecule exists for each of the
20 amino acids found in proteins.

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 22-11 Anticodons and tRNA Molecules 819

Amino acid Figure 22-19 A tRNA molecule.

attachment site The amino acid attachment site is
at the open end of the cloverleaf
39 end (the 3′ end), and the anticodon
A
59 end is located in the hairpin loop
C
C
opposite the open end.
G 59 end 39 end
U A
A U
G C
C G
G
A U G C CAG C
C C
UAAG G C G
C C GGUC
A U G
G
U GUUC C U A
A
C G
U A
C G
A U
G C
U C Anticodon
C A
C U U
Anticodon

a b

All tRNA molecules have the same general shape, and this shape is crucial to
how they function. Figure 22-19a shows the general two-dimensional “cloverleaf ”
shape of a tRNA molecule, a shape produced by the molecule’s folding and twist-
ing into regions of parallel strands and regions of hairpin loops. (The actual three-
dimensional shape of a tRNA molecule involves considerable additional twisting of
the “cloverleaf ” shape—Figure 22-19b.)
Two features of the tRNA structure are of particular importance:
1. The 3′ end of the open part of the cloverleaf structure is where an amino acid
covalently bonds to the tRNA. The carboxyl group of the amino acid reacts with
the 3′ OH group on the terminal nucleotide residue resulting in the formation of
an aminoacyl ester. Each of the different tRNA molecules is specifically recog-
nized by an aminoacyl tRNA synthetase enzyme. These enzymes also recognize
the one kind of amino acid that “belongs” with the particular tRNA and facili-
tates its bonding to the tRNA (see Figure 22-20).
2. The loop opposite the open end of the cloverleaf, called the anticodon loop,
consists of seven unpaired bases of which the middle three bases constitute the
anticodon. This anticodon recognizes and base pairs with an mRNA codon that
possesses a complementary three-base unit. An anticodon is a three-nucleotide
sequence on a tRNA molecule that is complementary to a codon on an mRNA
molecule.

Aminoacyl–tRNA Figure 22-20 An aminoacyl–

O
OH synthetase specific tRNA synthetase has an active site
+
for histidine for tRNA and a binding site for the
H3N CH C O–
particular amino acid that is to be
CH2 attached to that tRNA.
NH
N

Active site for

tRNAHistidine
Active site for
histidine

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820 Chapter 22 Nucleic Acids

Amino acid The interaction between the anticodon of the tRNA and the codon of the mRNA
leads to the proper placement of an amino acid into a growing peptide chain dur-
39 59 ing protein synthesis. This interaction, which involves complementary base pairing, is
shown in Figure 22-21.

Example 22-7
Determining Codon–Anticodon Relationships
tRNA
A tRNA molecule has the anticodon 5′ AAG 3′. With which mRNA codon will this
anticodon interact?
Solution
Anticodon The interaction between a codon and an anticodon has directionality (antiparallel)
mRNA A G U
59 39 considerations, that is,
U C A
39 Anticodon 59
Codon
59 Codon 39
Figure 22-21 The interaction
between anticodon (tRNA) and The given anticodon, with reversed directionality, is
codon (mRNA), which involves 3′ GAA 5′
complementary base pairing,
governs the proper placement of and its codon interaction, which involves complementary base pairing, is
amino acids in a protein.
Anticodon 39 GAA 59

Codon 59 CUU 39

The codon is, thus, 5′ CUU 3′.

Example 22-8
Determining Anticodon–tRNA Amino Acid Relationships
A tRNA molecule possesses the anticodon 5′ CGU 3′. Which amino acid will this
tRNA molecule carry?
Solution
Codons, rather than anticodons, are involved in the genetic code relationships. The
codon with which the anticodon 5′ CGU 3′ base pairs is 5′ ACG 3′. Remember, as
shown in Example 22-6, that the codon–anticodon pairing involves the anticodon
3′ UGC 5′ (the anticodon written in the 3′-to-5′ direction).

Anticodon 39 UGC 59

Codon 59 ACG 39

The amino acid that the codon ACG codes for (see Table 22-2) is Thr (Threonine).

Example 22-9
Determining Relationships Among DNA Base Sequences, mRNA Base Sequences,
Codons, Anticodons, and Amino Acids
A DNA template strand is read as follows:

39 ACG AAC CGA TAG GGA 59

Determine each of the following using this base sequence.
a. The base sequence in the DNA informational strand
b. The codons present in the mRNA transcribed from the DNA template strand
(­assuming that no introns are present)

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 22-11 Anticodons and tRNA Molecules 821

c. The tRNA anticodons that interact with the mRNA codons

d. The amino acids that the tRNA molecules carry
e. The structure of the peptide formed from the overall translation process
Solution
a. The DNA informational strand has bases complementary to those in the DNA
template strand.
Template strand 39 ACG AAC CGA TAG GGA 59

Informational strand 59 TGC TTG GCT ATC CCT 39

b. The mRNA bases will be the same as those in the informational strand, except that
U has replaced T. The codons are derived from the mRNA base sequence.

Informational strand 59 TGC TTG GCT ATC CCT 39

mRNA 59 UGC UUG GCU AUC CCU 39

Codons 59 UGC UUG GCU AUC CCU 39

c. The anticodon bases will be complementary bases of the codon bases.

Codons 59 UGC UUG GCU AUC CCU 39

Anticodons 39 ACG AAC CGA UAG GGA 59

Rewriting the anticodons in the 5′-to-3′ direction gives

Anticodons 59 AGG GAU AGC CAA GCA 39

d. The amino acids that the tRNAs carry are determined by codons rather than
anticodons. The genetic code is used to make the connection between codons and
amino acids.

Codons 59 UGC UUG GCU AUC CCU 39

Amino acids Cys Leu Ala Ile Pro

e. The peptide structure parallels the amino acid sequence obtained from the codon
sequence.

N-terminal end Cys–Leu–Ala–Ile–Pro C-terminal end

Section 22-11 Quick Quiz

1. Which of the following is an incorrect pairing of concepts?
a. tRNA and “amino acid carrier”
b. tRNA and “anticodon carrier”
c. tRNA and “codon carrier”
d. no correct response
2. Which of the following statements concerning the “cloverleaf ” shape of tRNA mol-
ecules is correct?
a. Four hairpin loops are present.
b. Three hairpin loops and one open end are present.
c. Two hairpin loops and two open ends are present.
d. no correct response
3. A tRNA molecule with the anticodon 5′ AAG 3′ will interact with which of the follow-
ing mRNA codons?
a. 3′ AAG 5′
b. 3′ UUC 5′
c. 5′ UUC 3′
d. no correct response

Answers: 1. c; 2. b; 3. b

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822 Chapter 22 Nucleic Acids

22-12 Translation: Protein Synthesis

L e a r n i n g F oc u s
Be familiar with how ribosomes, mRNA, rRNA, and tRNA are involved in the process of
­translation; be familiar with the five general steps of the translation part of protein synthesis.

Translation is the process by which mRNA codons are deciphered and a particular
­protein molecule is synthesized. The substances needed for the translation phase of
protein synthesis are mRNA molecules, tRNA molecules, amino acids, ribosomes,
and a number of different enzymes. A ribosome is an rRNA–protein complex that
serves as the site for the translation phase of protein synthesis.
The number of ribosomes present in a cell for higher organisms varies from hun-
dreds of thousands to even a few million. Recent research concerning ribosome struc-
ture suggests the following for such structures:

1. They contain four rRNA molecules and about 80 proteins that are packed
into two rRNA–protein subunits, one small subunit and one large subunit
(Figure 22-22).
2. Each subunit contains approximately 65% rRNA and 35% protein by mass.
3. A ribosome’s active site, the location where proteins are synthesized by one-at-a-
time addition of amino acids to a growing peptide chain, is located in the large
▶ rRNA molecules provide the ribosomal subunit. ◀
structural and functional founda- 4. The active site is mostly rRNA, with only one of the ribosome’s many protein
tion for ribosomes. components being present.
5. Because rRNA is so predominant at the active site, the ribosome is thought to be
an RNA enzyme (Section 21-1), that is, a ribozyme.
6. The mRNA involved in the translation phase of protein synthesis binds to the
small subunit of the ribosome.

The rRNA and tRNA involved in the translation phase of protein synthesis are
synthesized by transcription of DNA sequences just as is hnRNA/mRNA. However,
unlike mRNA molecules, they do not have the characteristics (chemical composition)
necessary for them to function as codon carriers.
There are five general steps to the translation process: (1) activation of tRNA,
(2) initiation, (3) elongation, (4) termination, and (5) post-translation processing.

Activation of tRNA
There are two steps involved in tRNA activation. First, an amino acid interacts with
an activator molecule (ATP; Section 23-3) to form a highly energetic complex. This
complex then reacts with the appropriate tRNA molecule to produce an activated
tRNA molecule, a tRNA molecule that has an amino acid covalently bonded to it at
its 3′ end through an ester linkage.

Figure 22-22 Ribosomes, which

contain both rRNA and protein,
have structures that contain two
subunits. One subunit is much
larger than the other.
Ribosomal Large subunit
subunits

Ribosome
Small subunit

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 22-12 Translation: Protein Synthesis 823

H O Ester linkage
OH
R C C O
5' 5'
NH
+ 3

tRNA Acylamino tRNA

(unactivated tRNA) (activated tRNA)

Initiation
The initiation of protein synthesis in human cells begins when mRNA attaches
itself to the surface of a small ribosomal subunit such that its first codon, which
is always the initiating codon AUG, occupies a site called the P site (peptidyl site)
­(Figure 22-23a). An activated tRNA molecule with an anticodon complementary to
the codon AUG attaches itself, through complementary base pairing, to the AUG
codon (Figure 22-23b). The resulting complex then interacts with a large ribosomal
subunit to complete the formation of an initiation complex (Figure 22-23c). (Since
the initiating codon AUG codes for the amino acid methionine, the first amino acid in
a developing human protein chain will always be methionine.)

Elongation
Next to the P site in an mRNA–ribosome complex is a second binding site called the
A site (aminoacyl site) (Figure 22-24a). At this second site the next mRNA codon
is exposed, and a tRNA with the appropriate anticodon binds to it (Figure 22-24b).
With amino acids in place at both the P and the A sites, the enzyme peptidyl trans-
ferase effects the linking of the P site amino acid to the A site amino acid to form a
dipeptide. Such peptide bond formation leaves the tRNA at the P site empty and the
tRNA at the A site bearing the dipeptide (Figure 22-24c).
The empty tRNA at the P site now leaves that site and is free to pick up
another molecule of its specific amino acid. Simultaneously with the release of
tRNA from the P site, the ribosome shifts along the mRNA. This shift puts the

Met Met
39 59 39 59

Large
Initiating subunit
codon at P site

UAC UAC
mRNA AUG AUG AUG

39 39 39

59 P site 59 P site 59 P site

Small subunit
a b c

Figure 22-23 Initiation of protein synthesis begins with the formation of an initiation complex.

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824 Chapter 22 Nucleic Acids

tRNA carrying
Met an amino acid
Met Gly
Codons
Ribosome
Anticodon
UA
C

UAC CCA
AUG GGU GCU AUG GGU
UUU GGU CUG CAU GCU UUU CUG CAU
GGU
39 39
59 A site 59 A site
P site mRNA
P site

a The initiation tRNA carrying the amino acid Met binds b A tRNA with amino acid 2 binds at the A site.
at the P site.

Met Ala Met Ala

Gly Gly

C
UA
CG
A CGA

UAC CCA CCA

AUG GGU G GGU

GCU UUU CUG CAU AU GCU UUU GGU CUG CAU
GGU
39 39
59 59 A site
A site
P site P site

c A peptide bond forms between amino acid 1 and amino d The first tRNA is released, the ribosome moves one codon
acid 2 as amino acid 1 moves from the P site to the A site. to the right, translocating the dipeptide to the P site,
and the tRNA with amino acid 3 occupies the A site.

Met

Gly Phe
Ala

AA
A
CCA CGA
GGU
AUG GCU UUU GGU CUG CAU
39
59
A site
P site

e Elongation continues as the dipeptide at the P site is

bonded to the amino acid at the A site to form a tripeptide.

Figure 22-24 The process of translation that occurs during protein synthesis. The anticodons of
tRNA molecules are paired with the codons of an mRNA molecule to bring the appropriate amino
acids into sequence for protein formation.

newly formed dipeptide at the P site, and the third codon of mRNA is now avail-
able, at site A, to accept a tRNA molecule whose anticodon complements this codon
▶ In elongation, the polypeptide (­Figure 22-24d). ◀ The movement of a ribosome along an mRNA molecule is called
chain grows one amino acid at a translocation. ­Translocation is the part of translation in which a ribosome moves down
time. an mRNA ­molecule three base positions (one codon) so that a new codon can occupy the
ribosomal A site.
Now a repetitious process begins. The third codon, now at the A site, accepts
an incoming tRNA with its accompanying amino acid; then the entire dipeptide at
the P site is transferred and bonded to the A site amino acid to give a tripeptide (see
­Figure 22-24e). The empty tRNA at the P site is released, the ribosome shifts along
▶ The process of ­translocation the mRNA, and the process continues. ◀
occurs at approximately The transfer of the growing peptide chain from the P site to the A site is an
50-­millisecond intervals, that is, example of an acyl transfer reaction, a reaction type first introduced in Section 16-19.
20 times per second.
­Figure 22-25 shows the structural detail for such transfer when Met is the amino acid
at the P site and Gly is the amino acid at the A site.

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 22-12 Translation: Protein Synthesis 825

NH2

CH3 S CH2 CH2 CH Met

Acyl group Met Gly O C

NH2 NH2 NH

CH3 S CH2 CH2 CH CH2 CH2 Gly

O C C O C O
tRNA Empty tRNA
O O OH O
Acyl transfer
reaction

Ribosome
UA C C C C UA C C C C

AUG GGG AU C AUG GGG AU C

39 39

59 59
mRNA

P site A site P site A site

Figure 22-25 The transfer of an amino acid (or growing peptide chain) from the ribosomal P site
to the ribosomal A site during translation is an example of an acyl transfer reaction.

Termination
The polypeptide continues to grow by way of translocation until all necessary amino
acids are in place and bonded to each other. Appearance in the mRNA codon
sequence of one of the three stop codons (UAA, UAG, or UGA) terminates the pro-
cess. No tRNA has an anticodon that can base pair with these stop codons. The poly-
peptide is then cleaved from the tRNA through hydrolysis.

Post-Translation Processing
Some modification of proteins usually occurs after translation. This post-translation
processing gives the protein the final form it needs to be fully functional. Some of the
aspects of post-translation processing are the following:
1. In most proteins, the methionine (Met) residue that initiated protein synthesis is
removed by a specialized enzyme in a hydrolysis reaction. A second hydrolysis
reaction releases the polypeptide chain from its tRNA carrier.
2. Some covalent modification of a protein can occur, such as the formation of di-
sulfide bridges between cysteine residues (Section 20-6).
3. Completion of the folding of polypeptides into their active conformations
occurs. Protein folding actually begins as the polypeptide chain is elongated on
the ribosome. For proteins with quaternary structure (Section 20-13), the various
components are assembled together. ◀ ▶ Research involving mice now
links misfolding of protein mol-
Recent research indicates that there may be a connection between synonymous ecules to neurological disorders.
codons within the genetic code (Section 22-10) and protein folding. It now appears When mice were purposely
that synonymous codons, even though they translate into the same amino acids dur- injected with misfolded versions
ing protein synthesis, have an effect on the way emerging proteins fold into their three- of certain proteins, they developed
neurological symptoms similar to
dimensional shapes (tertiary structure; Section 20-12) as they elongate and then leave those associated with ­Alzheimer’s
a ribosome. This means that two stretches of mRNA that differ only in synonymous and/or Parkinson’s disease in
codons can produce proteins with identical amino acid sequences but different fold- humans. The researchers hope
ing patterns. Two differently folded proteins would be expected to produce different to find new drugs that can block
biochemical responses within a cell when interacting with other substances; there is disease progression by interfering
with protein misfolding pathways.
now some evidence that this is the case.

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826 Chapter 22 Nucleic Acids

Efficiency of mRNA Utilization

Many ribosomes can move simultaneously along a single mRNA molecule (Figure 22-26).
In this highly efficient arrangement, many identical protein chains can be synthesized
almost at the same time from a single strand of mRNA. This multiple use of mRNA
molecules reduces the amount of resources and energy that the cell expends to synthesize
needed protein. Such complexes of several ribosomes and mRNA are called polyribo-
somes or polysomes. A polyribosome is a complex of mRNA and several ribosomes.
Chemistry at a Glance—Protein Synthesis: Transcription and Translation—sum-
marizes the steps in protein synthesis.
The focus on relevancy feature Chemical Connections 22-C—Antibiotic Protein
Synthesis Inhibitors—discusses how disruption of the protein synthesis process in
bacteria, through use of antibiotics, is an effective method for killing undesirable bac-
teria present in the human body.

Figure 22-26 Several ribosomes Large subunit Growing Secondary structure Complete
can simultaneously proceed along of ribosome protein begins to form. protein
a single strand of mRNA one
after another. Such a complex of
mRNA and ribosomes is called a
mRNA
polyribosome or polysome.
Ribosome
3' subunits are
5' released.

Ribosomes move along mRNA.

Small subunit
of ribosome

Section 22-12 Quick Quiz

1. Which of the following statements about ribosomes is correct?
a. The number of ribosomes in a cell seldom exceeds 50.
b. The active site of a ribosome contains mostly protein molecules.
c. Structurally, ribosomes have two rRNA–protein subunits.
d. no correct response
2. Which of the following events is not part of the translation phase of protein synthesis?
a. mRNAs carry amino acids to the ribosome active site
b. codon–anticodon interactions occur
c. an mRNA attaches itself to the small subunit of a ribosome
d. no correct response
3. The number of codon binding sites in an mRNA–ribosome complex that can be
­occupied at the same time by activated tRNA molecules is
a. 2
b. 3
c. 4
d. no correct response
4. A polyribosome is a complex that
a. contains four ribosomal subunits instead of the usual two
b. involves a ribosome and several mRNA molecules
c. involves an mRNA molecule and several ribosomes
d. no correct response
5. Which of the following is an activity that does not occur as part of post-translation
processing?
a. covalent modification through formation of disulfide bonds
b. completion of folding of polypeptide chains
c. elongation of a polypeptide chain
d. no correct response

Answers: 1. c; 2. a; 3. a; 4. c; 5. c

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 22-12 Translation: Protein Synthesis 827

Chemistry
at a Glance Protein Synthesis: Transcription and Translation

TRANSCRIPTION
PHASE Nuclear membrane

Nucleus Cytoplasm of cell

of cell

Step 1: Formation Step 2: Formation Step 3: mRNA Enters

of hnRNA of mRNA the Cytoplasm
DNA in the nucleus partially Introns are removed from The mRNA leaves the nucleus
unwinds to allow a strand of the hnRNA strand. and enters the cytoplasm.
hnRNA to be made.

TRANSLATION 3' end

Met
5' end
PHASE A Step 1: Activation of tRNA
C
C
G
U A
An amino acid interacts with ATP to
A
G
U
C
become highly energized. It then
A
G
C
U G C CAG
G
C forms a covalent bond with the 3' end
C
C
A U
C GGUC
UAAG G C
C
G
G
of a tRNA molecule. Amino acid–
tRNA pairing is governed by enzymes.
G
U GUUC C U A
A
C G
U A
C G
A U
G C
U C
C A
C U U

Anticodon Ile
Val
Met Gly
Met Glu Met
Gly Gln
Ribosome
Codons
UA
C

mRNA UA C C C A GUU
AUG GGU AU C AUG GGU AU C C AA UAA
GAA

P site A site

Step 2: Initiation Step 3: Elongation Steps 4 and 5: Termination and

The mRNA attaches to a Another tRNA with the second Post-Translation Processing
ribosome so that the first amino acid binds at the A site. The
codon (AUG) is at the P methionine transfers from the P site The polypeptide chain continues to lengthen
site. A tRNA carrying to the A site. The ribosome shifts to until a stop codon appears on the mRNA.
methionine attaches to the next codon, making its A site The new protein is cleaved from the last
the first codon. available for the tRNA carrying the tRNA.
third amino acid.
During post-translation processing, cleavage
of Met (the initiation codon) usually occurs.
S—S bonds between Cys units also can form.

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828 Chapter 22 Nucleic Acids

C h e m i cal Conn e ct i on s 2 2 - C

Antibiotic Protein Synthesis Inhibitors

Protein synthesis proceeds in the same general way in all Many, but not all, of the protein synthesis inhibitor
forms of life. The synthesis details are, however, less com- a­ ntibiotics now in use have names that end in “mycin.” The
plex for organisms such as bacteria. mode of action of some of these inhibitors is as follows:
Comparison of protein synthesis in bacteria with that in
1. Erythromycin: binds to the larger bacterial ribosome sub-
human cells shows the following similarities and differences:
unit, blocking the exit of a growing peptide chain.
1. In both cases, ribosomes are the sites for protein syn- 2. Terramycin: blocks the A-site location on the ribosome,
thesis. Human ribosomes are much larger than bacterial preventing the attachment of amino-acid-carrying
ribosomes. tRNAs.
2. In bacteria, the initiator codon is N-formylmethionine. 3. Streptomycin (see accompanying structural diagram):
In human cells, it is methionine. binds to the smaller bacterial ribosome subunit causing
3. In bacteria, mRNA translation begins while the mRNA a shape change, which in turn causes a misreading of
is still being transcribed from DNA. In human cells, mRNA information.
mRNA translation begins only after transcription.
NH
4. Bacteria/mRNAs undergo very little processing after B
being transcribed and are very short-lived. In some cases, NH
B HN NH2
degradation of mRNA begins before completion of tran-
H2N NH
scription. In human cells, transcribed mRNA (hnRNA)
undergoes considerable processing before mature RNA OH OH
is formed. OH
The differences between bacterial and human protein O
O
synthesis are sufficient to make bacterial protein synthesis
an ideal target for antibacterial chemotherapy, that is, use CHO
of antibiotics to kill bacteria. Many antibiotics now in use H3C
are bacterial protein synthesis inhibitors (see accompanying HO HO
photo). O O
HN
HO CH3
HO
Streptomycin
(a trisaccharide derivative)

4. Neomycin: binds to the smaller bacterial ribosome subu-

nit in a manner similar to streptomycin.
5. Chloramphenicol: binds to the ribosome and interferes
with the formation of peptide bonds between amino acids.
Simon Dack/Alamy

The well-known penicillin family of antibiotics are not

protein synthesis inhibitors but, rather, enzyme inhibitors
(Section 21.9).
In a reversal of the process in which human interven-
tion (drugs) disrupt bacterial protein synthesis, bacterial
Erythromycin and similar drugs inhibit protein synthesis in intervention (diseases) can block human protein synthesis.
bacteria. ­Several protein synthesis toxins produced by microorgan-
isms are known that shut down human protein synthesis
These inhibitors disrupt bacterial protein synthesis with fatal results. Diphtheria is caused by a protein synthesis
but do not affect human cell protein synthesis. This is be- inhibitor produced by a bacterium that grows in the upper
cause the inhibitors target the bacterial ribosome, which is respiratory tract of an infected person. This inhibitor affects
much smaller than human ribosomes. Human ribosomes the chain elongation phase of protein synthesis. Diphtheria
are unsuitable targets for the antibiotics because of their was a major cause of death in children before the advent of
larger size. effective immunization procedures.

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 22-13 Mutations 829

22-13 Mutations
L e a r n i n g F oc u s
Know the characteristics for both point and frameshift mutations; be familiar with common
types of mutagens.

A mutation is an error in base sequence in a gene that is reproduced during DNA

­replication. Such errors alter the genetic information that is passed on during tran-
scription. The altered information can cause changes in amino acid sequence during
protein synthesis. Sometimes, such changes have a profound effect on an organism.
Two common types of mutations are (1) a point mutation and (2) a frameshift
mutation. A point mutation is a mutation in which one base in a DNA base sequence is
replaced with another base. Such a mutation is often also called a substitution muta-
tion. Illustrative of this one-base change in a DNA sequence is the following:

Original DNA TAGCAC

C has replaced G
Point Mutated DNA TACCAC

The effect of a point mutation can vary from no effect to a change in primary protein
structure to termination of protein synthesis, as is illustrated in Example 22-10.

E x a m pl e 2 2 - 1 0
Predicting the Effect of a Point Mutation
Predict the change that occurs in amino acid identity when each of the following point
mutations occur on 3′-to-5′ DNA base segments.
a. GAG is point mutated to GAA .   b.  AAA is point mutated to AAT .
c. ATA is point mutated to ATT .
Solution
The same analysis applies to each of the three parts of this example.
1. Determine the DNA informational strand base sequence that is complementary to
the given DNA template strand base sequence.
2. Determine the mRNA base sequence using the informational strand base sequence.
They will be the same except that the RNA base U has replaced the DNA base T.
3. Using the genetic code, determine the amino acid that is specified by the mRNA
base sequence (codon).
a. Unmutated base sequence: GAG n CTC n CUC n Leu
template informational mRNA amino
strand strand acid

Mutated base sequence: GAA n CTT n CUU n Leu

template informational mRNA amino
strand strand acid
This is a silent mutation. Amino acid identity is not affected, as both mRNA
­codons code for the same amino acid.
b. Unmutated base sequence: AAA n TTT n UUU n Phe
template informational mRNA amino
strand strand acid

Mutated base sequence: AAT n TTA n UUA n Leu

template informational mRNA amino
strand strand acid
The point mutation has produced a codon that codes for a different amino acid.
(continued)

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830 Chapter 22 Nucleic Acids

c. Unmutated base sequence: ATA n TAT n UAU n Tyr

template informational mRNA amino
strand strand acid
Mutated base sequence: ATT n TAA n UAA n stop codon
template informational mRNA amino
strand strand acid

The point mutation has produced a stop codon, resulting in termination of protein
synthesis.

A frameshift mutation is a mutation that inserts or deletes a base in a DNA mol-

ecule base sequence. Such a change affects not only the base triplet located at the
insertion or deletion point but also all triplets that follow in the sequence. This
contrasts with a point mutation where only one triplet is affected. Figure 22-27
shows the effects that a frameshift mutation can have on an amino acid sequence in
a protein.
A mutagen is a substance or agent that causes a change in the structure of a gene.
Radiation and chemical agents are two important types of mutagens. Radiation, in
the form of ultraviolet light, X-rays, radioactivity (Chapter 11), and cosmic rays,
has the potential to be mutagenic. Ultraviolet light from the sun is the radiation that
causes sunburn and can induce changes in the DNA of skin cells. Sustained exposure
to ultraviolet light can lead to skin cancer problems.
Chemical agents can also have mutagenic effects. Nitrous acid (HNO2) is a muta-
gen that causes deamination of heterocyclic nitrogen bases. For example, HNO2 can
convert cytosine to uracil.

Figure 22-27 Changes that (a) Normal DNA and correct amino acid sequence
occur in amino acid sequence
resulting from a frameshift DNA (template strand) 39 59
mutation that involves deletion of
A A C C T C G T C A C G A T T
a base from a DNA sequence. Transcription
U U G G A G C A G U G C U A A
mRNA 59 39

Translation

Original amino Stop

acid sequence Leu Glu Gln Cys

(b) Frameshift mutation involving removal of a base and the resulting change in amino acid sequence
C

DNA (template strand) 39 59

A A C C T C G T A C G A T T
Transcription
U U G G A G C A G U G C U A
mRNA 59 39

Translation

Changed amino
acid sequence Leu Glu His Ala A ...

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 22-14 Nucleic Acids and Viruses 831

NH2 O
H
N HNO2 N

N O N O
A A
H H
Cytosine Uracil

Deamination of a cytosine that was part of an mRNA codon would change the
codon; for example, CGG would become UGG.
A variety of chemicals—including nitrites, nitrates, and nitrosamines—can form
nitrous acid in the body. The use of nitrates and nitrites as preservatives in foods such
as bologna and hot dogs is a cause of concern because of their conversion to nitrous
acid in the body and subsequent possible damage to DNA.
Fortunately, the body has repair enzymes that recognize and replace altered bases.
Normally, the vast majority of altered DNA bases are repaired, and mutations are
avoided. Occasionally, however, the damage is not repaired, and the mutation persists.
The focus of relevancy feature Chemical Connections 22-D—Erythropoietin
(EPO): Red Blood Cells, Mutations, and Athletic Performance—discusses a situation
where a mutation involving a protein hormone that regulates red blood cell produc-
tion became an advantage for an individual.

Section 22-13 Quick Quiz

1. Which of the following describes the effect of a point mutation on amino acid identity
in a protein?
a. The identity of one amino acid must change.
b. The identity of one amino acid may change.
c. The identity of two amino acids must change.
d. no correct response
2. Which of the following describes the effect of a frameshift mutation?
a. All mRNA codons change.
b. Some, but not all, mRNA codons change.
c. There is no change in mRNA codons.
d. no correct response
3. Which of the following statements applies to both point and frameshift mutations?
a. A base is removed from a DNA template strand.
b. A base is added to a DNA template strand.
c. A base is substituted for another base in a DNA template strand.
d. no correct response

Answers: 1. b; 2. b; 3. d

22-14 Nucleic Acids and Viruses

L e a r n i n g F oc u s
Describe a common method by which a virus infects a cell; describe how a vaccine works.

Viruses are very small disease-causing agents that are considered the lowest order
of life. Indeed, their structure is so simple that some scientists do not consider them
truly alive because they are unable to reproduce in the absence of other organisms.
NIBSC/SPL/Science Source

­Figure 22-28 shows an electron microscope image of an influenza virus.

A virus is a small particle that contains DNA or RNA (but not both) surrounded by
a coat of protein and that cannot reproduce without the aid of a host cell. Viruses do not
possess the nucleotides, enzymes, amino acids, and other molecules necessary to replicate
their nucleic acid or to synthesize proteins. To reproduce, viruses must invade the cells of
another organism and cause these host cells to carry out the reproduction of the virus.
Such an invasion disrupts the normal operation of cells, causing diseases within the host Figure 22-28 An electron micro-
organism. The only function of a virus is reproduction; viruses do not generate energy. scope image of an influenza virus.

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832 Chapter 22 Nucleic Acids

C h e m i cal Conn e ct i on s 2 2 - D

Erythropoietin (EPO): Red Blood Cells, Mutations, and Athletic Performance

Erythropoietin (pronounced ih-rith-roh-poi-eet-n) is a

protein hormone produced by the kidney, and to a lesser
extent by the liver, that promotes the development of
red blood cells and initiates the synthesis of hemoglobin
­(Section 20-16), the molecule within red blood cells that
transports oxygen. It is a glycoprotein (Section 20-18).
Because of its somewhat difficult to pronounce name,
erythropoietin is usually referred to using the shortened
designation EPO.
The primary structure of EPO has been determined, and
using this information and recombinant DNA technology
(Section 22-15), synthetically produced EPO as well as sev-
eral synthetic EPO analogs have been made. One of these
synthetic analogs, epoetin alfa (Epo; lower case p and o), is
one of the most widely used drugs created through recom-
binant DNA technology. Approved by the FDA in 1989, it
is widely used in the treatment of certain types of anemia
to increase red blood cell production. Most kidney dialysis
patients now receive Epo.

Kyodo/Newscom
EPO and red blood cells have some interesting connec-
tions to athletes and athletic performance. A major limit-
ing factor in athletic performance is the oxygen-carrying
capacity of blood. This capacity is directly related to the
number of hemoglobin molecules present which in turn
depends on the number of red blood cells present. EPO is switch” for red blood cell production. Hence, the elevated
a controlling factor for both hemoglobin and red-blood- red blood cell level in persons with this protein mutation.
cell count and thus has a direct relationship to athletic Despite the previously mentioned anemia-related health
performance. Two situations relating to the connection benefits associated with synthetic EPO production, there
between red blood cell levels and athletic performance are is also a downside to its production. Synthetic EPO was
now considered. “discovered” by endurance athletes trying to gain an illegal
The first situation involves cross-skiing events at the advantage over their competitors. Obviously, enhanced oxy-
1964 Winter Olympics held in Innsbruck, ­Austria. At gen carrying ability because of increased red blood cell pro-
these Olympic games, a Finnish cross-country skier duction translates into enhanced muscle performance. EPO
named Eero Maentyranta won three gold medals. and its synthetic analogs are believed to have been widely
A major reason for his unusually strong performance used in certain sports in the 1990s, most notoriously in Tour
was that his blood contained 25%–50% more hemoglobin de France cycling events, without detection. These syn-
than is found on average in blood. Thus, the oxygen-­ thetic compounds are metabolized quickly and are almost
carrying capacity of his blood was much greater than identical to the body’s naturally produced EPO. Direct test-
that of his competitors. His enhanced oxygen-delivery ing for EPO was not available until 2000. The 2002 Winter
system was not due, however, to use of illegal substances, ­Olympics was the first event where samples testing positive
as would be expected in today’s athletic environment, but for EPO were found.
rather to a rare genetic defect (mutation), common in the EPO abuse by athletics is now known to be dangerous
Maentyranta family, that results in abnormally high lev- and several deaths have occurred because of its use. Water
els of red blood cells. Thus, this skier’s “­oxygen advan- loss associated with extreme exertion coupled with EPO use
tage” was a natural advantage rather than an illegally produces a thickening of the blood that can reach dangerous
obtained advantage. levels. The thickened blood puts great strain on the heart.
Several years later, genetic studies carried out at the EPO and its analogs are now banned substances in athletic
­University of Helsinki determined that the Maentyranta competitions. Back to the Finnish cross-country skier Eero
family’s genetic disorder involved a mutated protein respon- Maentyranta. Because he had been born with an elevated
sible for red blood cell production. The mutated protein con- red blood cell condition, his body had adapted to the condi-
tained only 480 amino acids rather than the normal 550; a tion, and it became an advantage, without negative effects,
70 amino acid segment was missing. It was then determined in athletic competitions. The serious disadvantages of EPO
that the missing amino acid segment contained the “off use by other athletics far outweigh any advantages obtained.

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