chapter 15 From Gene

to Protein

FPO

Dannielle Tegeder, Chromosome Constellation, need date.

Finding the Messenger lem is easy to solve: A message is sent from one
location to the other. In addition, the message must
and Breaking the Code
be translated from German, the language in which

W
e live in a global economy. The headquar-
ters of a corporation may be located in
one country—say, Germany—but the
company’s factories may be located elsewhere—say,
the United States. Immediately there is a problem:
Decisions made in Germany need to be communi-
cated to employees in the United States. This prob-
the decision was made, to English, the language in
which the decision must be implemented.
Eukaryotic cells face similar challenges. Genes
work by controlling the production of proteins.
Whereas genes are located in the nucleus of the cell,
their protein products are made on ribosomes,
which are located outside of the nucleus, in the

252

cytoplasm. How
does a gene control from
a distance how a ribo-
some constructs a protein?
Like our imaginary corporate
headquarters, the gene does this by
sending a message. What is the
chemical messenger that carries the
gene’s instructions from the nucleus to the
ribosome? And once the message reaches
■ MAIN MESSAGE
By controlling the production of
proteins, genes play a key role in
determining the organism’s pheno-
type.
A Model of a tRNA Molecule
Transfer RNA molecules like this one read the genetic code.
the ribosomes, how do the
ribosomes “read” it?
This last question
highlights another
similarity between
cells and our
imaginary inter-
national corpora-
tion: To be effec-
tive, the
information con-
tained in genes must
be translated from one “language” (that of DNA,
which is based on its four nucleotide bases) to
another (that of proteins, which is based on the 20
amino acids they contain). In the mid-1950s, biolo-
gists working on this problem realized that cells
must have a “genetic code” that allows the instruc-
tions of the gene to be translated from the language
of DNA to the language of proteins. The discovery
of how cells do this was one of the crowning
achievements of twentieth-century science: the
breaking of the genetic code.
254 UNIT 3 Genetics
■ KEY CONCEPTS
1. Most genes contain instructions for building proteins.
The DNA sequence of a gene encodes the amino acid
sequence of its protein product.
2. A few genes encode RNA molecules as their final product.
3. Two steps are required to go from gene to protein: tran-
scription and translation.
4. In eukaryotic cells, transcription occurs in the nucleus
and produces a messenger RNA copy of the information
stored in the gene.
C
hapters 12 through 14 have described how
genes are inherited, where they are located (on
chromosomes), and what they are made of
(DNA). But we have yet to describe how genes work.
How do genes store the information needed to build
their final products, proteins? How does the cell use
that information? Knowing how genes work can help
us understand how mutations produce new pheno-
types, including disease phenotypes. We begin this
chapter by discussing how genetic information is en-
coded in genes and how the cell uses that information
to build proteins. We then discuss how a change to a
gene can change an organism’s phenotype.
Genes Encode Proteins
Genes work by controlling the production of proteins.
For most genes, the relationship between gene and pro-
tein is direct: The gene contains instructions for how to
build a particular protein. Some genes have an indirect
relationship to proteins. Rather than encoding a partic-
ular protein, these genes specify how to build ribonu-
cleic acid (RNA) molecules that help the cell construct
proteins.
Proteins are essential to life. They are used by cells
and organisms in many ways: Some provide structural
support, others transport materials, still others defend
against disease-causing organisms. In addition, the
many chemical reactions on which life depends are con-
trolled by a crucial group of proteins, the enzymes.
Enzymes and other proteins influence so many features
of the organism that they, along with the environment,
determine the organism’s phenotype.
Early clues that genes work by controlling the pro-
duction of proteins came at the beginning of the twen-
tieth century from the work of British physician
Archibald Garrod, who studied several inherited
5. Translation occurs in the cytoplasm and converts the
sequence of bases in an mRNA molecule to the sequence
of amino acids in a protein.
6. Mutations can alter the sequence of amino acids in a
gene’s protein product. Such changes, in turn, can alter the
protein’s function. Although changes in protein function
are usually harmful, occasionally they benefit the organism.
human metabolic disorders. In 1902, he argued that
these disorders were caused by an inability of the body
to produce specific enzymes. Garrod was particularly
interested in alkaptonuria, a condition in which the
urine of otherwise healthy infants turns black when
exposed to air. He proposed that infants with alkap-
tonuria had a defective version of an enzyme that ordi-
narily would break down the substance that caused
urine to turn black. Garrod did not stop there; he and
his collaborator, William Bateson, went on to suggest
that in general, genes worked by controlling the pro-
duction of enzymes.
Genes contain information for the synthesis
of RNA molecules
Garrod and Bateson were on the right track, but they
were not entirely correct: Genes control the production
of all proteins, not just enzymes. In addition, as men-
tioned above, a few genes do not directly specify pro-
teins. Rather, these genes specify as their final product
one of several RNA molecules used in the construction
of proteins. Thus, directly and indirectly, genes control
the production of proteins.
As we will see shortly, even genes that specify pro-
teins make an RNA molecule as their initial product.
Thus, modifying the definition in Chapter 12, we can
redefine a gene as a sequence of DNA that contains
information for the synthesis of one of several types of
RNA molecules used to make proteins.
Three types of RNA are involved
in the production of proteins
The nucleic acids DNA and RNA (see Chapter 5) play
key roles in the construction of proteins. Several types
of RNA, as well as many enzymes and other proteins,

are required for the cell to make proteins. As already
described, DNA controls the production of all these
essential molecules, so DNA controls all aspects of pro-
tein production.
Cells use three types of RNA molecules to construct
proteins: ribosomal RNA (abbreviated rRNA), messen-
ger RNA (mRNA), and transfer RNA (tRNA). The func-
tion of each kind of RNA is defined in Table 15.1 and
discussed in more detail in the sections that follow. But
first we describe several general differences between the
structure of RNA and the structure of DNA. Whereas
DNA molecules are double-stranded, most RNA mol-
ecules are single-stranded. Overall, the structure of a
single strand of RNA is similar to the structure of a sin-
gle strand of DNA. RNA is composed of a long string
of nucleotides covalently bonded together. Each
nucleotide, in turn, is composed of a sugar–phosphate
backbone and one of four nitrogen-containing bases
(Figure 15.1). However, the nucleotides in RNA and
DNA differ in two respects: (1) RNA uses the sugar
ribose, whereas DNA uses the sugar deoxyribose; and
(2) in RNA, the base uracil (U) replaces the DNA base
thymine (T). The other three bases (A, C, and G) are the
same in RNA and DNA.
■ Genes work by controlling the production of pro-
teins. A gene contains information for the synthesis
of one of several types of RNA molecules used to make
proteins. Three types of RNA and many enzymes and
other proteins are required for this process. RNA con-
sists of a single strand of nucleotides, each composed
of a sugar–phosphate backbone and one of four nitro-
gen-containing bases: A, C, G, or U.
How Genes Control
the Production of Proteins
In both prokaryotes and eukaryotes,
genes specify the production of proteins
in two steps: transcription and translation. 15.1
In transcription, an RNA molecule is
Type of RNA molecule
made from the DNA sequence of a gene.
If the gene specifies the production of Ribosomal RNA (rRNA)
rRNA or tRNA, its transcription produces
those molecules as the final product. If the
Messenger RNA (mRNA)
gene specifies a protein, however, its tran-
Transfer RNA (tRNA)
scription produces an mRNA molecule,
which in turn specifies the amino acid
sequence of a protein. In translation,
CHAPTER 15 From Gene to Protein 255
RNA is single-
stranded.
P
In RNA, U replaces
U the DNA base T.
P Phosphate
P
G U
Sugar
(ribose) Base
P
U
Nucleotide
P In RNA, nucleotides use the sugar
A ribose rather than the sugar
deoxyribose that is used in DNA.
P
U
P Figure 15.1 The Structure
C of RNA
RNA molecules are composed
of a single strand of
P nucleotides, each of which
G consists of a phosphate, a
ribose sugar, and a base (ade-
nine, cytosine, guanine, or
uracil).
rRNA, mRNA, and tRNA molecules direct the synthe-
sis of a given gene’s protein product.
We will discuss transcription and translation in detail
later in the chapter. First, however, let’s consider how
genes work from the perspective of information flow.
We will describe the flow of genetic information in
eukaryotes. Events are similar in prokaryotes except
that, because they lack a nucleus, both genes and ribo-
somes are located in the cytoplasm.
RNA Molecules and Their Functions
Function
Major component of ribosomes, the molecular
machines that make the covalent bonds that
link amino acids together into a protein
Specifies the order of amino acids in a protein
Transfers the correct amino acid to the ribosome,
on the basis of the information encoded in the
mRNA
256 UNIT 3 Genetics
For a protein to be made, the information in the gene
must be sent from the gene, which is located in the nucle-
us, to the site of protein synthesis. As we learned in
Chapter 6, proteins are synthesized at ribosomes, which
are located in the cytoplasm (Figure 15.2). Ribosomes are
made up of rRNA and proteins. The information in the
gene is transferred from the nucleus to the ribosome by
mRNA. This transfer of information is made possible by
transcription, in which the sequence of bases in mRNA
is copied directly from the DNA sequence of a gene.
Because it is a direct copy of the gene’s DNA sequence,
mRNA provides the ribosome with all the information
that is contained in the gene.
Once the mRNA molecule arrives at the ribosome, the
information on how to build the protein must be trans-
lated from the language of DNA (nucleotide bases) to
the language of proteins (amino acids). The information
is translated at the ribosomes by tRNA molecules. One
portion of each tRNA molecule can bind to one specific
sequence of mRNA, while another portion can bind to
and carry one specific amino acid. The specificity of
these binding rules is essential because it allows the mes-
sage in mRNA to be translated into the exact sequence
of amino acids that is called for by the gene.
Figure 15.2 The Flow of Genetic Information
Genetic information flows from DNA to RNA to protein in
two steps, transcription and translation. Transcription pro-
duces an mRNA molecule, which then moves to the ribo-
some, where translation occurs and the protein is made.
Different amino acids in the protein being constructed at
the ribosome are represented by different colors. This illus-
tration shows the flow of information in a eukaryotic cell.
An mRNA copy of the gene is
made in the nucleus.
DNA
Nuclear
envelope
Transcription
mRNA
Nucleus
Cytoplasm
fpo Eukaryotic cell Amino acids are linked to one another
at the ribosome to form a protein.
■ Two steps are required for the synthesis of proteins:
transcription and translation. In transcription, an mRNA
molecule is made using the DNA sequence of the gene.
In translation, rRNA, mRNA, and tRNA molecules direct
protein synthesis. Information for the synthesis of a
protein flows from the gene, located in the nucleus,
to the site of protein synthesis, the ribosome, located
in the cytoplasm.
Transcription: From DNA to RNA
Transcription is the synthesis of an RNA molecule using
the DNA sequence of a gene as a template. As we saw
above, transcription produces all the kinds of RNA mol-
ecules we have mentioned; here, we focus on the tran-
scription of mRNA from genes that encode proteins.
Transcription is somewhat similar to DNA replication
in that one strand of DNA is used as a template from
which a new strand—in this case, a strand of mRNA—
is formed. However, transcription differs from DNA
replication in three important ways. First, a different
enzyme guides the process: Whereas the enzyme used
in DNA replication is DNA polymerase, the key enzyme
in transcription is RNA polymerase. Second, whereas
the entire DNA molecule is duplicated in DNA replica-
tion, in transcription only the small portion of a DNA
molecule that includes a particular gene is transcribed
into mRNA. Finally, whereas the process of DNA repli-
cation produces a double-stranded DNA molecule, the
process of transcription produces a single-stranded
mRNA molecule.
Transcription begins when the RNA
polymerase enzyme binds to a region of
DNA that is called a promoter. Pro-
moters contain specific base sequences
to which RNA polymerase can bind.
Once bound to the promoter, the RNA
polymerase enzyme unwinds the DNA
Translation double helix and separates the two
strands. Then the enzyme begins to con-
struct an mRNA molecule (Figure 15.3).
As discussed earlier, RNA molecules
consist of four bases: adenine (A), cyto-
Ribosome
sine (C), guanine (G), and uracil (U).
These four bases pair with the four
bases in DNA according to specific
rules: A in RNA pairs with T in DNA,
C in RNA pairs with G in DNA, G in
 CHAPTER 15 From Gene to Protein 257

DNA
Figure 15.3 Overview of Transcription

Transcription Translation
RNA polymerase
mRNA

1 Transcription begins when

RNA polymerase binds to
the promoter DNA.

RNA polymerase
fpo
New mRNA Template strand
DNA of gene strand of DNA

Direction of movement
of RNA polymerase
Promoter DNA
(in yellow)
Terminator DNA
(in red)

an mRNA molecule synthesized from this DNA tem-

plate would have the sequence

AAUACCGUGGC
2 A new mRNA strand is produced
as RNA polymerase moves Synthesis of an mRNA molecule from the DNA tem-
down the DNA template. plate continues until the RNA polymerase enzyme
3 Transcription ends when reaches a sequence of bases called a terminator, at which
RNA polymerase reaches point transcription ends and the newly formed mRNA
the terminator DNA. molecule separates from its DNA template. The two
strands of the DNA template then bond back to each
other, ready to be used again when needed by the cell.
Messenger RNA molecules produced by transcription
will carry the information from the gene to the ribosome,
where the protein specified by the gene is built. First,
however, the newly formed mRNA molecule must often
be modified before it is used. In eukaryotes, most genes
contain internal sequences of bases called introns that
do not specify part of the protein encoded by the gene
(Figure 15.4). Introns must be removed from the initial
mRNA product if the protein encoded by the gene is to
function properly.
RNA pairs with C in DNA, and U in RNA pairs with A
in DNA. These base-pairing rules determine the
sequence of bases in the mRNA molecule that is made ■ In transcription, an mRNA molecule is synthesized
from a DNA template. For example, if the DNA from a gene’s DNA template. In eukaryotes, genes con-
sequence were tain internal sequences of DNA called introns that must
be removed from the initial mRNA product.
TTATGGCACCG
 258 UNIT 3 Genetics

Figure 15.4 Removal of Introns by

Eukaryotic Cells
Introns are regions of DNA
within a gene that do not
Before mRNA molecules can be used,
encode any part of the gene’s enzymes in the nucleus must remove non-
Coding coding sequences (introns) and link the
protein product.
region Intron remaining coding sequences together.
DNA

Transcription

Initial RNA
product
The Genetic Code
Genes are composed of DNA and con-
Introns removed
sist of a sequence of the four bases ade-
nine, cytosine, guanine, and thymine.
The information in a gene is encoded in
its sequence of bases. As we learned in
fpo Coding regions linked the previous section, the gene’s DNA
sequence is used during transcription as
mRNA a template to produce an mRNA mole-
cule. How does the sequence of bases in
Coding sequence mRNA encode, or specify, the sequence
Nucleus Messenger RNA
moves out of the of amino acids in a protein? From the
nucleus to the late 1950s to the mid-1960s, geneticists
cytoplasm, where worked feverishly to figure out the code
Nuclear it is used to guide
envelope protein synthesis.
that accomplishes this task. By 1966, the
genetic code had been broken (Figure
Nuclear pore Cytoplasm 15.5).
In the genetic code, an amino acid is
specified by a nonoverlapping sequence
of three nucleotide bases in an mRNA
molecule. Each group of three bases in
mRNA is called a codon. For example,
UAA, UAG, and UGA do as Figure 15.6 shows, if a portion of an
Figure 15.5 The Genetic Code not code for an amino acid. mRNA molecule con-
Translation stops when
these codons are reached. sisted of the sequence
Second letter of codon
UUCACUCAG, the
U C A G first codon (UUC)
Like arginine, most
UUU Phenyl- UAU UGU U
UCU Tyrosine amino acids are would specify one
UUC alanine UCC UAC UGC Cysteine C specified by more
U Serine amino acid (phenylala-
UUA UCA UAA Stop codon UGA Stop codon A than one codon.
Leucine UCG nine), the next codon
UUG UAG Stop codon UGG Tryptophan G
(ACU) would specify a
CAU U second amino acid
CUU CCU Histidine CGU
CAC
First letter of codon

CUC CCC CGC C (threonine), and the last codon (CAG)

Third letter of codon

C Leucine Proline Arginine

CUA CCA CAA CGA A would specify a third amino acid (glut-
CUG CCG CAG Glutamine CGG
G amine). There are four possible bases at
AUU ACU AAU AGU U each of the three positions of a codon,
AUC Isoleucine ACC AAC Asparagine AGC Serine C so there are a total of 64 possible codons
A AUA Threonine
ACA AAA AGA A (4 × 4 × 4 = 64).
AUG Methionine; ACG AAG Lysine AGG Arginine G When reading the code, the cell
start codon
GAU U begins at a fixed starting point, called a
GUU GCU GGU
GUC GCC GAC Aspartate GGC C start codon (usually the codon AUG),
G Valine Alanine Glycine and ends at one of several stop codons
GUA GCA GAA GGA A
GUG GCG GAG Glutamate GGG (such as UGA or UAA) (see Figure 15.5).
fpo G
By beginning at a fixed point, the cell

In transcription, the DNA
sequence of a gene is used to
produce an mRNA molecule.
DNA strand
Transcription
mRNA
Codon Codon
Translation
Protein Phenyl- Threo-
alanine nine
In translation, the genetic code is
used to determine the amino acid
that corresponds to each codon… …and the amino acids are
linked to one another at the
ribosome to form a protein.
Figure 15.6 How Cells Use the Genetic Code
ensures that the message from the gene does
not become scrambled. To see why this is
important, use Figure 15.5 to determine the
amino acid sequence that would results if the
sequence UUCACUCAG in Figure 15.6 were
read in codons that began with the second U,
not the first.
■ The information in a gene is encoded in
its sequence of bases. In the genetic code,
an amino acid is specified by a codon, a
nonoverlapping sequence of three nucleo-
tide bases in an mRNA molecule. When
reading the genetic code, the cell begins at
a fixed starting point, thus ensuring that the
message from the gene does not become
scrambled.
CHAPTER 15 From Gene to Protein 259
Translation: From mRNA to Protein
Gene
The genetic code provides the cell with the equiv-
alent of a dictionary with which to translate the
language of DNA into the language of proteins.
The conversion of a sequence of bases in mRNA
to a sequence of amino acids in a protein is called trans-
fpo lation. Translation is the second major step in the process
by which genes specify proteins (see Figure 15.2). It
occurs at the ribosomes, which are composed of sever-
al different sizes of rRNA molecules and more than 50
different proteins. The ribosomes are molecular
machines that make the covalent bonds that link amino
acids together into a protein. As a major component of
ribosomes, rRNA plays a central role in protein synthe-
sis (see Table 15.1).
Transfer RNA molecules also play a crucial role in the
synthesis of proteins at ribosomes. There are several types
Codon
of tRNA molecules, but they all have a similar structure
with two binding sites (Figure 15.7). First, each tRNA
molecule has a particular sequence of nucleotide bases,
called an anticodon, that can bind to a particular mRNA
Gluta- codon. Each tRNA molecule also has a site that can bind
mine
to a particular amino acid. Each tRNA molecule can carry
the specific amino acid that is called for by the mRNA
codon to which it can bind. If this were not the case, the
genetic code would not work.
Figure 15.7 Transfer RNA (tRNA)
Translation is accomplished by tRNA molecules, which bind
to specific mRNA codons and to specific amino acids. Shown
here are a computer model (at left) and a simplified illustra-
tion (at right) of a tRNA molecule. Similar regions in the
computer model and simplified illustration of a tRNA mole-
cule are drawn in matching colors. The site at which tRNA
binds to an mRNA codon is called the anticodon.
Amino acid
Serine
Amino acid
attachment
site
tRNA
Anticodon (binds
to a specific
codon on mRNA)
Codon (on an
mRNA molecule)
fpo mRNA
260 UNIT 3 Genetics

Figure 15.8 Translation Step 1: Translation begins when

mRNA binds to the ribosome.

A tRNA molecule carrying A tRNA molecule

Methionine
the amino acid methionine carrying glycine binds
binds to the start codon. to the second codon.

Ribosome
Transcription Translation

Cytoplasm mRNA
Stop codon
Start codon

The ribosome links the first

amino acid (methionine) to the
second (glycine) to form the
Glycine beginning of an amino acid chain.
For translation to occur, an mRNA molecule
must first bind to a ribosome. Once this binding
has occurred, translation begins at the AUG start
codon that is nearest to the region where mRNA
is bound to the ribosome. Here’s how the amino
fpo
mRNA
acid chain of the protein is built. Stop codon
First, a tRNA molecule binds to the AUG
Start codon
codon, bringing with it the
amino acid methionine Step 2: As the ribosome moves one
(Figure 15.8). Next, anoth- codon at a time, tRNA molecules The first tRNA
er tRNA molecule, carrying bind to mRNA, allowing the is released.
ribosome to link the amino acids
the appropriate amino acid in the correct order.
(in this example, glycine) Serine
binds to the second codon
on the mRNA molecule (GGG). The ribosome
then forms a covalent bond between the first
amino acid (methionine) and the second amino
acid (glycine). The ribosome then moves to the
next mRNA codon, and the first tRNA—the one mRNA
bound to AUG—is released. Stop codon
Once the first tRNA is released, a tRNA mole-
Start codon
cule binds to the third codon, bringing with it the Completed
third amino acid of the growing amino acid chain Later amino
serine. The ribosome links the first two amino acid chain
acids to the third one, and
releases the second tRNA.
This process continues until Step 3: When the ribosome reaches a stop
codon, the mRNA and the completed amino
a stop codon is reached, at acid chain both separate from the ribosome.
which point the mRNA
molecule and the complet-
ed amino acid chain both
separate from the ribosome. The new pro- mRNA
tein then folds into its compact, specific Start codon
three-dimensional shape. Stop codon
 CHAPTER 15 From Gene to Protein 261

Insertion or deletion mutations occur when a sin-

■ In translation, a sequence of bases in mRNA is con-
verted into a sequence of amino acids in a protein.
Transfer RNA molecules carry the specific amino acids
called for by the mRNA to the ribosome, which links
them together to form a protein molecule.
The Effect of Mutations
on Protein Synthesis
In Chapter 13 we discussed two types of mutations:
those that affect individual genes and those that alter
the number or structure of chromosomes. Both types of
mutations alter the DNA of a cell. In general, we can
define a mutation as a change in either the sequence or
the amount of DNA found in a cell. Mutations range
in extent from a change in the identity of a single base
pair to the addition or deletion of one or more chro-
mosomes.
In this section we describe how mutations affect pro-
gle base is inserted into or deleted from a DNA
sequence. Such mutations alter the identity of many of
the amino acids in the encoded protein (see Figure 15.9),
which usually prevent the protein from functioning
properly. When an insertion or deletion mutation occurs,
it is said to cause a frameshift. A genetic frameshift is
similar to what happens if you accidentally record the
answer to a question twice on the answer sheet of a mul-
tiple choice test: All the answers from that point forward
are likely to be wrong, since each is an answer to the pre-
vious question. Similarly, a frameshift shifts all the
codons by one base, scrambling the message.
Normal gene
DNA template
mRNA
Iso-
Protein Valine Serine Serine leucine Proline

tein synthesis. Here we focus on mutations that occur in

the portions of a gene that encode proteins, rather than In a substitution mutation, a single Mutations
base is changed. This change can
mutations that occur in introns or mutations that affect
entire chromosomes.
cause one amino acid to be substi-
tuted for another, as happened here.
fpo
Base substitution
Many mutations alter a single base pair
Many mutations are changes in a single base pair of a
gene’s DNA sequence. There are three major types of
such mutations: substitution, insertion, and deletion
mutations. In a substitution mutation, one base is Valine Serine Serine Valine Proline
changed to another at a single position in the DNA
sequence of the gene. In the substitution mutation
The insertion of a single base
shown in Figure 15.9, for example, the sequence of the shifts the translation of the
gene is changed when a thymine (T) is replaced by a codons, causing a frameshift.
cytosine (C). As the figure shows, this particular change The deletion of a single base also
causes the substitution of one amino acid for another causes a frameshift (not shown).
because the mRNA codons made from the DNA Base insertion
sequences TAA and CAA encode different amino acids
(isoleucine and valine, respectively).
Not all substitution mutations lead to changes in the
amino acid sequence of a protein. For example, although
a change in the DNA sequence from GGG to GGA would
Valine Serine Serine Tyrosine Serine
alter the mRNA sequence from CCC to CCU, since both
CCC and CCU code for the same amino acid, glycine (see
Figure 15.5), this change would not alter the amino acid
Figure 15.9 Effects of DNA Mutations
sequence of the protein. In such cases, the substitution Changes to the sequence of bases in a gene can change the
mutation is said to be “silent” because it produces no sequence of amino acids in the gene’s protein product. DNA
change in the structure of the protein, and thus no change bases, RNA bases, and amino acids that change as a result of
in the phenotype. a mutation are shown in red.
262 UNIT 3 Genetics

is a substitution of a single base and does not result in

Insertions or deletions of a series
of bases are common
Mutations can alter more than one base pair of the DNA
sequence of a gene. For example, from two to thousands
of bases can be inserted within a DNA sequence. Unless
the number of bases that are inserted is a multiple of
three (the length of a complete codon), such an insertion
will cause a frameshift, usually preventing the protein
from functioning properly. Even if no frameshift occurs,
the insertion of extra bases into a gene causes extra
amino acids to be added to the protein being built, often
destroying protein function and hence harming the
organism.
Mutations can cause a change
in protein function
Mutations alter the DNA sequence of a gene, which in
turn alters the sequence of bases in an mRNA molecule
made from the gene. Changes to the sequence of bases
in mRNA can have a wide range of effects. If the change
the substitution of one amino acid for another, the struc-
ture and function of the protein are not changed. Even
if one or a few amino acids of the protein are changed,
there may be little or no effect. For example, changes that
do not alter the region of the protein that binds to its sub-
strate may not affect protein function. However, amino
acid changes that alter the binding region of a protein
usually do change how the protein works (see the box
on p. 000). Such changes often are harmful to the organ-
ism because they decrease or destroy protein function.
On rare occasions, changes to the binding region of a
protein benefit the organism by improving its efficien-
cy, or by causing the protein to take on a new and use-
ful function.
■ Many mutations are caused by the substitution,
insertion, or deletion of a single base pair. Insertions or
deletions of a series of bases are also common.
Mutations can change the function of a gene’s protein
product.

■ BIOLOGY IN OUR LIVES

Coffee by Design: All the Taste, None of the Jolt

J
ava. The aroma of a hot cup of cof-
fee, its taste, and the “kick start” it
provides makes coffee a beverage
of choice for many people. But coffee
has a dark side, with side effects that
include increased blood pressure,
insomnia, anxiety, tremors, heart pal-
pitations, and gastrointestinal distur-
bances. Because many people love
coffee but are sensitive to its side
effects, there has been increasing
demand for decaffeinated coffee.
Unfortunately, flavors and aromas
can be lost in the decaffeination
process, making decaf a less attrac-
tive choice than it otherwise would
be. And decaf is not 100 percent caf-
feine-free, so for some people, even
a single cup of decaf after dinner can
mean a long night with the jitters.
Coffee lovers, take heart. Re-
searchers have now isolated the gene
Decaf Anyone?
Genetic engineering techniques may
soon produce a cup of decaf with as
much flavor as regular coffee.
for caffeine synthase, an enzyme that
controls the final two steps in the caf-
feine biosynthesis pathway in the cof-
fee plant. With this gene in hand, it
should now be possible to develop
caffeine-free coffee that retains all of
its flavor. For example, genetic engi-
neering techniques could be used to
add an intron to the caffeine synthase
gene, thereby destroying the function
of the enzyme it encodes and render-
ing the coffee plant unable to make
caffeine. The coffee that resulted
would be 100 percent caffeine-free
and should keep all of its flavor, since
caffeine is odorless and tasteless.
To some people, coffee without
the kick will always be an oxymoron.
But for people who are strongly
affected by caffeine or who are trying
to reduce their coffee consumption,
the availability of a fully flavored
decaf would be a welcome develop-
ment. A cup of decaf could then be
savored like a regular cup of coffee,
but without the aftereffects. If a jump-
start were desired, there would still
be the option of a cup of caffeinated
coffee. And it would taste just as
good as decaf.
 CHAPTER 15 From Gene to Protein 263

Putting It Together: lation (see Figure 15.2). In transcription, the sequence of

From Gene to Phenotype bases in the DNA of a gene is used as a template to pro-
duce an mRNA molecule. The cell then transports this
Humans have approximately 35,000 genes. More than mRNA molecule to a ribosome, where translation
99 percent of these genes code for the amino acid occurs. In translation, the sequence of bases in the
sequences of proteins; the rest specify RNA molecules mRNA molecule is used to synthesize the gene’s protein
such as tRNA or rRNA. Here we review the major steps product.
in how cells go from gene to protein to phenotype, focus- The proteins encoded by genes are essential to life. A
ing on genes that encode proteins. However, it is impor- mutation in a gene can alter the sequence of amino acids
tant to remember that transcription—the first step in the in the gene’s protein product, and this change can dis-
process that leads from gene to protein—is similar in all able or otherwise alter the function of the protein. When
genes, including the small percentage that specify tRNA a critical protein is disabled, the entire organism may be
and rRNA molecules. Translation does not occur for harmed. For example, in people who suffer from the
genes that specify tRNA or rRNA because the tRNA and genetic disease sickle-cell anemia, a single base in the
rRNA molecules produced by such genes are the gene’s gene that encodes hemoglobin is altered (Figure 15.10).
final product. Hemoglobin is a protein that functions in the transport
Chromosomes contain many genes. Each gene on a of oxygen by red blood cells. The red blood cells of peo-
chromosome is composed of DNA and consists of a ple with sickle-cell anemia are curved and distorted
sequence of the four bases adenosine (A), cytosine (C), under low oxygen conditions, such as those found in nar-
guanine (G), and thymine (T). The particular sequence row blood vessels like our capillaries. The distorted red
of bases in the DNA of the gene specifies the amino acid blood cells clog these narrow blood vessels, thereby lead-
sequence of the gene’s protein product. ing to a wide range of serious effects, including heart and
As we have discussed in this chapter, the two major kidney failure.
steps from gene to protein are transcription and trans- In sickle-cell anemia, a gene mutation alters the gene’s
protein product, which in turn produces a change in the
organism’s phenotype. A similar chain of events occurs
for other genes. Overall, the phenotype of an organism
Normal hemoglobin Sickle-cell is determined by the organism’s proteins and by the
DNA hemoglobin DNA
environment (see Chapter 12).
Because genes control the produc-
tion of proteins, genes play an
Only one base differs from the sequence important role in determining the
of the normal hemoglobin allele…
Transcription phenotype of the organism.
…causing the GAG codon in normal hemoglobin
mRNA mRNA mRNA to be replaced by a GUG codon…
■ Proteins are essential to life. In
conjunction with the environment,
fpo …which in turn causes
proteins determine an organism’s
phenotype. Because genes control
Translation glutamate to be replaced the production of proteins, they
by valine.
play a key role in determining an
Normal hemoglobin Sickle-cell hemoglobin organism’s phenotype.
Glutamate Valine

The replacement of glutamate

Normal red blood cells
by valine causes individuals with
sickle-cell anemia to have
abnormally shaped red blood cells.
A sickled red blood cell
Figure 15.10 A Small Genetic Change
Can Have a Large Effect
Sickle-cell anemia is caused by a
change in a single base. People with
sickle-cell anemia usually die before
they reach childbearing age.
264 UNIT 3 Genetics
■ HIGHLIGHT
The Evolving Genetic Code
The genetic code lies at the heart of the process by which
genes make proteins: It provides the “dictionary” that
cells use to translate the language of DNA into the lan-
guage of proteins. As we have learned in this chapter,
the genetic information stored in genes is first tran-
scribed into mRNA molecules, then translated by tRNA
molecules. Transfer RNA molecules are able to translate
the genetic code because one portion of their structure
binds to a specific mRNA codon while another portion
binds to the specific amino acid called for by that mRNA
codon.
We might expect the consequences of any change in
the genetic code to be disastrous. For example, consid-
er what would happen if a particular type of tRNA mol-
ecule began carrying the wrong amino acid. For every
protein made by every cell in the body, whenever the
codon recognized by that tRNA was translated, the
wrong amino acid would be inserted into the protein
that was being built. As a result, the function of many
proteins would probably be destroyed, which would kill
or severely harm the organism.
This line of reasoning suggests that once the genetic
code reached its current form, early in the history of life,
it should have remained “frozen” in place because any
changes to it would be so harmful. This strong empha-
sis on the unchanging nature of the genetic code explains
why it is often called a universal code, common to all
life.
All organisms do have a similar genetic code, and
many use the exact same genetic code, the one shown in
Figure 15.5. But the genetic code is not really “frozen.”
Instead, it has slowly evolved, or changed over time. In
six species of yeasts, for example, CUG codes for serine
instead of leucine. In the mitochondria of many organ-
isms, AUA codes for methionine instead of isoleucine.
Such departures from the genetic code are not limited to
yeasts and mitochondria; bacteria, protists, and even
humans violate portions of the code. In total, 15 of the
64 codons—almost 25 percent—have changed their
meaning at least once throughout the history of life.
How did the genetic code evolve without killing the
organisms in which the changes occurred? One answer
to this question is that much of the genetic code is
“redundant” in the sense that several codons have the
same meaning—that is, they call for the same amino acid
(see Figure 15.5). In some cases, organisms do not use
one of the redundant codons at all, nor do they produce
the tRNA molecules that are usually associated with the
unused codon. If an organism no longer uses a particu-
lar codon, that codon can change its meaning without
damaging the organism.
Such changes appear to have happened repeatedly,
albeit very slowly, during the history of life. Early in the
history of life, all organisms probably did have the same
genetic code. But since that time, the genetic code, like
all other aspects of life, has evolved and continues to
evolve.
■ The genetic code has evolved slowly over time. It
can change without killing the organism because dif-
ferent codons call for the same amino acid, and in
some cases, some of these redundant codons are not
used.
SUMMARY
How Genes Work
■ Genes work by controlling the production of proteins.
■ Most genes encode proteins.
■ A few genes do not encode proteins, but rather specify as
their final product one of several RNA molecules that are
used to synthesize proteins.
■ Three types of RNA (rRNA, mRNA, and tRNA) and many
enzymes and other proteins are required for the cell to
make proteins.
■ RNA consists of a single strand of nucleotides, each com-
posed of a ribose sugar–phosphate backbone and one of
four nitrogen-containing bases: adenine (A), cytosine (C),
guanine (G), or uracil (U).
How Genes Control the Production of Proteins
■ In both prokaryotes and eukaryotes, two steps are
required for the synthesis of proteins: transcription and
translation.
■ In transcription, an RNA molecule is made using the DNA
sequence of the gene.
■ In translation, rRNA, mRNA, and tRNA molecules direct
protein synthesis.
■ In eukaryotes, information for the synthesis of a protein
flows from the gene, located in the nucleus, to the site of
protein synthesis, the ribosome, located in the cytoplasm.
Transcription: From DNA to RNA
■ In transcription, an mRNA molecule is synthesized from a
gene’s DNA template.
■ The mRNA molecule is constructed using the DNA
sequence of the gene according to specific base-pairing
 CHAPTER 15 From Gene to Protein 265

rules: A in DNA pairs with U in RNA, T in DNA pairs KEY TERMS

with A in RNA, and C pairs with G.
■ In eukaryotes, genes contain internal sequences of DNA anticodon p. 000 messenger RNA (mRNA)
(introns) that must be removed from the initial mRNA codon p. 000 p. 000
product if the protein encoded by the gene is to function deletion mutation p. 000 promoter p. 000
properly. ribosomal RNA (rRNA) p. 000
frameshift p. 000
The Genetic Code gene p. 000 substitution mutation p. 000
■ The information in a gene is encoded in its sequence of genetic code p. 000 transcription p. 000
bases. insertion mutation p. 000 transfer RNA (tRNA) p. 000
■ In the genetic code, an amino acid is specified by a intron p. 000 translation p. 000
nonoverlapping sequence of three nucleotide bases, called
a codon, in an mRNA molecule.
■ When reading the genetic code, the cell begins at a fixed CHAPTER REVIEW
starting point, thus ensuring that the message from the
gene does not become scrambled.
Self-Quiz
Translation: From mRNA to Protein 1. For genes that specify a protein, what molecule carries
■ In translation, a sequence of bases in mRNA is converted information from the gene to the ribosome?
into a sequence of amino acids in a protein. a. DNA
■ Translation occurs at the ribosomes, which are composed b. mRNA
of rRNA and more than 50 different proteins. c. tRNA
d. rRNA
■ Ribosomes are molecular machines that make the covalent
bonds that link amino acids together into a protein. 2. During translation, the nucleotide bases in mRNA are
read _____ at a time to produce a protein.
■ Transfer RNA molecules carry the specific amino acids a. one
called for by the mRNA to the ribosome. b. two
c. three
The Effect of Mutations on Protein Synthesis d. four
■ Many mutations are caused by the substitution, insertion, 3. Which molecule carries the amino acid called for by
or deletion of a single base pair of a gene’s DNA sequence. mRNA to the ribosome?
■ Insertion or deletion of a single base pair causes a a. rRNA
frameshift, which usually destroys the function of the b. tRNA
gene’s protein product. c. codon
d. DNA
■ Insertions or deletions of a series of bases are also com-
mon. 4. In transcription, which of the following molecules is pro-
duced?
■ Mutations can change the function of a gene’s protein
a. mRNA
product.
b. rRNA
Putting It Together: From Gene to Phenotype c. tRNA
d. all of the above
■ More than 99 percent of genes specify proteins.
5. A portion of the DNA sequence of a gene has the
■ Proteins are essential to life. In conjunction with the envi- nucleotide bases CGGATAGGGTAT. What is the sequence
ronment, proteins determine an organism’s phenotype. of amino acids specified by this DNA sequence?
■ Because genes control the production of proteins, genes a. alanine-tyrosine-proline-isoleucine
play a key role in determining an organism’s phenotype. b. arginine-tyrosine-tryptophan-isoleucine
c. arginine-isoleucine-glycine-tyrosine
Highlight:The Evolving Genetic Code d. none of the above
■ The genetic code has evolved slowly over time. 6. What molecular machine makes the covalent bonds that
■ The genetic code can change without killing the organism link the amino acids of a protein together?
because different codons call for the same amino acid and, a. tRNA
in some cases, particular codons are not used. b. mRNA
c. rRNA
d. ribosome
266 UNIT 3 Genetics
Review Questions
1. What is a gene?
2. What are the functions of the three types of RNA used by
cells to make proteins: rRNA, tRNA, and mRNA?
Gene Therapy Bounces Back
In the past 50 years, science has re-
vealed that genes work by control-
ling the production of proteins. Our
knowledge of how genes work has
raised a tantalizing prospect: Could
we reach inside our cells and repair
genes that cause disease? Scientists
in France appear to have done just
that in a groundbreaking study on
SCID-X1, a lethal human immune
deficiency disease that leaves its
victims vulnerable to many kinds
of infections.
The French scientists used a
technique known as gene therapy,
which seeks to correct genetic dis-
orders by fixing the genes that
cause the disorder. This technique,
which is still in the early stages of
development, has recently fallen on
Evaluating “The News”
1. Despite more than a decade of
effort, gene therapy has produced
few success stories. Should society
continue to fund gene therapy
research, which is relatively expen-
sive but may, in the long run, allow
us to fix otherwise incurable genetic
diseases? Or would our money be
spent more wisely on low-cost pre-
ventative measures that we know
can reduce the frequency of AIDS,
cancer, and other human diseases?
3. Summarize the key steps in transcription and translation.
4. Why is it essential that tRNA be able to bind to both an
amino acid and an mRNA codon?
5. Describe the flow of genetic information from gene to phe-
notype.
hard times: It has produced few un-
qualified success stories, and a gene
therapy patient died within the past
few months, apparently as a result
of the therapy. The lack of progress
and the recent death have led many
to argue that gene therapy is both a
scientific failure and unsafe.
The new results from France
may provide the boost gene thera-
py needs to bounce back. SCID-X1
is caused by a gene that produces a
defective version of a protein, the
usual version of which plays a crit-
ical role in the development of two
types of white blood cells used in
the human immune system, T cells
and natural killer cells. The French
scientists successfully inserted a
corrected version of this gene into
2. Gene therapy has been criticized for
promising too much and delivering
too little since its inception in the
early 1990s. Is this a fair criticism
for a technology in the early stages
of development?
3. Many people think it is ethically
wrong for people to use modern
genetic techniques to modify the
genes of organisms, including our-
selves. The modification of genes is
two patients, aged 8 and 11
months, suffering from SCID-X1.
Three years later, the results are
very encouraging: The numbers of
T and natural killer cells in the pa-
tients are up to normal levels, sug-
gesting that they will be able to live
a healthy and disease-free life.
That’s good news for the patients
and their families. And the news
will also be welcomed by recently
beleaguered gene therapy advo-
cates, who argue that despite the in-
evitable setbacks associated with
any new technology, gene therapy
holds more potential than any other
area of medicine to provide cures
for human genetic disease.
a key component of gene therapy.
In general, do you think it is ethi-
cally acceptable for people to modi-
fy the genes of organisms? In par-
ticular, do you think gene therapy,
which strives to cure human genet-
ic diseases, is ethically acceptable?
Why or why not? If you find gene
therapy ethically acceptable, are
there modifications of human genes
that you would not find ethical?