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3: DNA Consists of Two Complementary and Antiparallel Nucleotide Strands That Form a Double Helix

3: DNA Consists of Two Complementary and Antiparallel Nucleotide Strands That Form a Double Helix

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DNA: The Chemical Nature of the Gene

H
C
N1
HC

2

6
3

C
5
4

H
C

N

7

N3

8 CH
9

C

HC

N
H

N

N1
HC

2

3

N

C

5
4

C
HN1

7

8 CH

C

NH2

O
N
9

N
H

H2N

Adenine (A)

CH

Pyrimidine
(basic structure)

NH2
6

1

CH

5
6

N

Purine
(basic structure)

C

2

4

C

2

6
3

C

5
4

C

N

N3

7

8 CH

C

N

9

N
H

Guanine (G)

O

C
O

2

4
1

O

C
CH
5
6

HN3

CH

N
H

Cytosine (C)

C
O

2

4
1

C
5
6

CH3

C
HN3

CH

N
H

Thymine (T)
(present in DNA)

C
O

2

4
1

CH

5
6

CH

N
H

Uracil (U)
(present in RNA)

8.8 A nucleotide contains either a purine or a pyrimidine base. The atoms of the rings in the
bases are assigned unprimed numbers.

This difference gives rise to the names ribonucleic acid (RNA)
and deoxyribonucleic acid (DNA). This minor chemical difference is recognized by all the cellular enzymes that interact
with DNA or RNA, thus yielding specific functions for each
nucleic acid. Furthermore, the additional oxygen atom in the
RNA nucleotide makes it more reactive and less chemically
stable than DNA. For this reason, DNA is better suited to
serve as the long-term repository of genetic information.
The second component of a nucleotide is its nitrogenous base, which may be of two types—a purine or a
pyrimidine (Figure 8.8). Each purine consists of a six-sided
ring attached to a five-sided ring, whereas each pyrimidine
consists of a six-sided ring only. Both DNA and RNA contain
two purines, adenine and guanine (A and G), which differ
in the positions of their double bonds and in the groups
attached to the six-sided ring. Three pyrimidines are common in nucleic acids: cytosine (C), thymine (T), and uracil
(U). Cytosine is present in both DNA and RNA; however,
thymine is restricted to DNA, and uracil is found only in
RNA. The three pyrimidines differ in the groups or atoms
attached to the carbon atoms of the ring and in the number

of double bonds in the ring. In a nucleotide, the nitrogenous
base always forms a covalent bond with the 1Ј-carbon atom
of the sugar (see Figure 8.7). A deoxyribose or a ribose sugar
and a base together are referred to as a nucleoside.
The third component of a nucleotide is the phosphate
group, which consists of a phosphorus atom bonded to four
oxygen atoms (Figure 8.9). Phosphate groups are found in
every nucleotide and frequently carry a negative charge,
which makes DNA acidic. The phosphate group is always
bonded to the 5Ј-carbon atom of the sugar (see Figure 8.7)
in a nucleotide.
The DNA nucleotides are properly known as deoxyribonucleotides or deoxyribonucleoside 5Ј-monophosphates.
Because there are four types of bases, there are four different
kinds of DNA nucleotides (Figure 8.10). The equivalent
RNA nucleotides are termed ribonucleotides or ribonucleoside 5Ј-monophosphates. RNA molecules sometimes contain additional rare bases, which are modified forms of the
four common bases. These modified bases will be discussed
in more detail when we examine the function of RNA molecules in Chapter 10.


ϪO 9 P " O


Phosphate
8.9 A nucleotide contains a phosphate group.

Concepts
The primary structure of DNA consists of a string of nucleotides.
Each nucleotide consists of a five-carbon sugar, a phosphate, and
a base. There are two types of DNA bases: purines (adenine and
guanine) and pyrimidines (thymine and cytosine).

201

202

Chapter 8

NH2
N

N

ϪO 9 P 9 O 9 CH

2

O



H2N

2

O

H

H

H
OH

H

2

O

H

H

H

Deoxyadenosine
5؅-monophosphate
(dAMP)

ϪO 9 P 9 O 9 CH

O
H

OH

H

Deoxyguanosine
5؅-monophosphate
(dGMP)

N

O



O

H
H

O

H

H

H

H

Deoxythymidine
5؅-monophosphate
(dTMP)

N

O


2

H
OH

N

ϪO 9 P 9 O 9 CH

O

H

NH2
CH3

HN

N

N

ϪO 9 P 9 O 9 CH

O

H

N

HN

N

N



O

O

H
OH

H

Deoxycytidine
5؅-monophosphate
(dCMP)

8.10 There are four types of DNA nucleotides.

✔ Concept Check 4

Secondary Structures of DNA

How do the sugars of RNA and DNA differ?

The secondary structure of DNA refers to its three-dimensional configuration—its fundamental helical structure.
DNA’s secondary structure can assume a variety of configurations, depending on its base sequence and the conditions
in which it is placed.

a. RNA has a six-carbon sugar; DNA has a five-carbon sugar.
b. The sugar of RNA has a hydroxyl group that is not found in the
sugar of DNA.
c. RNA contains uracil; DNA contains thymine.
d. DNA’s sugar has a phosphorus atom; RNA’s sugar does not.

Polynucleotide strands DNA is made up of many
nucleotides connected by covalent bonds, which join the 5Јphosphate group of one nucleotide to the 3Ј-carbon atom of
the next nucleotide (Figure 8.11). These bonds, called phosphodiester linkages, are strong covalent bonds; a series of
nucleotides linked in this way constitutes a polynucleotide
strand. The backbone of the polynucleotide strand is composed of alternating sugars and phosphates; the bases project
away from the long axis of the strand. The negative charges
of the phosphate groups are frequently neutralized by the
association of positive charges on proteins, metals, or other
molecules.
An important characteristic of the polynucleotide strand
is its direction, or polarity. At one end of the strand, a free
(meaning that it’s unattached on one side) phosphate group is
attached to the 5Ј-carbon atom of the sugar in the nucleotide.
This end of the strand is therefore referred to as the 5Ј end.
The other end of the strand, referred to as the 3Ј end, has a free
OH group attached to the 3Ј-carbon atom of the sugar.
RNA nucleotides also are connected by phosphodiester linkages to form similar polynucleotide strands (see
Figure 8.11).

Concepts
The nucleotides of DNA are joined in polynucleotide strands by
phosphodiester bonds that connect the 3Ј-carbon atom of one
nucleotide to the 5Ј-phosphate group of the next. Each polynucleotide strand has polarity, with a 5Ј direction and a 3Ј direction.

The double helix A fundamental characteristic of DNA’s
secondary structure is that it consists of two polynucleotide
strands wound around each other—it’s a double helix. The
sugar–phosphate linkages are on the outside of the helix, and
the bases are stacked in the interior of the molecule (see Figure 8.11). The two polynucleotide strands run in opposite
directions—they are antiparallel, which means that the 5Ј
end of one strand is opposite the 3Ј end of the other strand.
The strands are held together by two types of molecular
forces. Hydrogen bonds link the bases on opposite strands
(see Figure 8.11). These bonds are relatively weak compared
with the covalent phosphodiester bonds that connect the
sugar and phosphate groups of adjoining nucleotides on the
same strand. As we will see, several important functions of
DNA require the separation of its two nucleotide strands,
and this separation can be readily accomplished because of
the relative ease of breaking and reestablishing the hydrogen
bonds.
The nature of the hydrogen bond imposes a limitation
on the types of bases that can pair. Adenine normally pairs
only with thymine through two hydrogen bonds, and cytosine normally pairs only with guanine through three hydrogen bonds (see Figure 8.11). Because three hydrogen bonds
form between C and G and only two hydrogen bonds form
between A and T, C–G pairing is stronger than A–T pairing.
The specificity of the base pairing means that, wherever there
is an A on one strand, there must be a T in the corresponding position on the other strand, and, wherever there is a G
on one strand, a C must be on the other. The two polynucleotide strands of a DNA molecule are therefore not identical but are complementary DNA strands.

203

DNA: The Chemical Nature of the Gene

DNA polynucleotide strand

RNA polynucleotide strand

T–A pairs have two
hydrogen bonds.
CH3
–O

HC
O

N

H2C 5’
H

C

H
N

C

A

C

H

HC

O

O

N

H
H

H

G

C

N

O

H

N

A

H

H

H

N

C

O

H
3’

N

O

H

H

3’
H

H

O

C

C

N
H

C

N
C

H

O

N
CH

C

G

C

N

N

N

H

H

H

O

P

H
H

H

OH

H

O

N

O
H2C 5’

N

HC

C

H

O

OH

N
H
H

H

N

C
HC
N
O

C

C

N

C
O

H
H

O

OH

O–

The strands run in opposite
directions; they are antiparallel.

8.11 DNA and RNA consist of polynucleotide strands.

The second force that holds the two DNA strands
together is the interaction between the stacked base pairs.
These stacking interactions contribute to the stability of
the DNA molecule but do not require that any particular
base follow another. Thus, the base sequence of the DNA
molecule is free to vary, allowing DNA to carry genetic
information.

H

C

H

O

H

C

A

N

H

P

N
C

O

H
3’

O

N

C
N

H

H2C 5’

H2C 5’

O

G

N

O

3’
H

C

H

P

H
3’

O
C

O

H
H
3’
O

–O

O

H

N

HC

C

H2C 5’

O–

P

H

C–G pairs have three
hydrogen bonds.
DNA has deoxyribose
sugar (no oxygen here).

H2C 5’
O

C

O

H
H

O

H

H

H

HC

H

O

O

O

H2C 5’

H

RNA has ribose sugar
(an OH group here).

O

–O

CH

CH

N

n

P

O

O–

P

H

H

H

O

N

C
H

O
CH

T

N

C

N

O

C

C
N

O

CH 3

O

C

C
C

H

U

H

O

P

n

n

directio

O

N

N

–O

C

OH

O

directio
5’-to-3’

HC

3’
H

H

3’

H2C 5’

H

O

H2C 5’

H
O

H

P

H

H

H

O

H
H

directio
5’-to-3’

5’-to-3’

H
H
3’
O

CH

O–

P

N

C
H

O

C

N

H

C

N

C

C

H

A phosphodiester
linkage connects the
5’-phosphate group
and the 3’-OH group
of adjoining nucleotides.

O

H

N

C

O

H

H2C 5’

O

O

N

H2C 5’

O

HN

O

P
O

O 3’

H

N

H

N

–O

N

C

C

C

O

H
3’

H

H

N

H2C 5’

CH

C

H

O

P

–O

N

H

O
–O

N

–O

N

O

H

3’

H

C

T

O

H

H

O

C

O

P

In RNA, uracil (U)
replaces thymine (T).

✔ Concept Check 5
The antiparallel nature of DNA refers to
a. its charged phosphate groups.
b. the pairing of bases on one strand with bases on the other
strand.
c. the formation of hydrogen bonds between bases from opposite
strands.
d. the opposite direction of the two strands of nucleotides.

Concepts

Different secondary structures As we have seen, DNA

DNA consists of two polynucleotide strands. The sugar–phosphate
groups of each polynucleotide strand are on the outside of the
molecule, and the bases are in the interior. Hydrogen bonding joins
the bases of the two strands: guanine pairs with cytosine, and adenine pairs with thymine. The two polynucleotide strands of a DNA
molecule are complementary and antiparallel.

normally consists of two polynucleotide strands that are
antiparallel and complementary (exceptions are singlestranded DNA molecules in a few viruses). The precise threedimensional shape of the molecule can vary, however,
depending on the conditions in which the DNA is placed
and, in some cases, on the base sequence itself.

H

204

Chapter 8

The three-dimensional structure of DNA described by
Watson and Crick is termed the B-DNA structure (Figure
8.12). This structure exists when plenty of water surrounds
the molecule and there is no unusual base sequence in the
DNA—conditions that are likely to be present in cells. The
B-DNA structure is the most stable configuration for a random sequence of nucleotides under physiological conditions, and most evidence suggests that it is the predominate
structure in the cell.
B-DNA is an alpha helix, meaning that it has a righthanded, or clockwise, spiral. There are approximately 10 base
pairs (bp) per 360-degree rotation of the helix; so each base
pair is twisted 36 degrees relative to the adjacent bases (see
Figure 8.12b). The base pairs are 0.34 nanometer (nm) apart;
so each complete rotation of the molecule encompasses 3.4
nm. The diameter of the helix is 2 nm, and the bases are perpendicular to the long axis of the DNA molecule. A spacefilling model shows that B-DNA has a slim and elongated
structure (see Figure 8.12a). The spiraling of the nucleotide
strands creates major and minor grooves in the helix, fea-

Direction of helix

28Å

(a) A form

(b) B form

(c) Z form

8.13 DNA can assume several different secondary structures.
[After J. M. Berg, J. L. Tymoczko, and L. Stryer, Biochemistry, 6th ed.
(New York: W. H. Freeman and Company, 2002), pp. 785, 787.]

(b) 5’ end
O–

–O

3’ end

O

P

HO

O
C

G
A

T
C

G
G

T

The DNA backbone is
deoxyribose sugars
linked by phosphate.

C
T

G
A

T

G

C
T

(a)

A
C

G

e

G

ov

or

o
gr

T

in

C

M

T

Phosphorus

Bases

0.34
nm

C

A
G

A

e

ov

Hydrogen
Carbon in
sugar–
phosphate
backbone

3.4 nm

2 nm
A

Oxygen

C

A

r

o
aj

o
gr

A
G

T

Concepts

C

M

O

OH

3’ end

tures that are important for the binding of some proteins
that regulate the expression of genetic information (see
Chapter 12).
Another secondary structure that DNA can assume is
the A-DNA structure, which exists if less water is present.
Like B-DNA, A-DNA is an alpha (right-handed) helix
(Figure 8.13a), but it is shorter and wider than B-DNA
(Figure 8.13b) and its bases are tilted away from the main
axis of the molecule. There is little evidence that A-DNA
exists under physiological conditions.
A radically different secondary structure, called Z-DNA
(Figure 8.13c), forms a left-handed helix. In this form, the
sugar–phosphate backbone zigzags back and forth, giving
rise to its name. A Z-DNA structure can result when DNA is
placed in a high-salt solution. It can arise under physiological conditions if the molecule contains particular base
sequences, such as stretches of alternating C and G
nucleotides. Recently, researchers have found that Z-DNAspecific antibodies bind to regions of the DNA that are being
transcribed into RNA, suggesting that Z-DNA may play
some role in gene expression.

–O

P

O

O–

5’ end

8.12 B-DNA consists of an alpha helix with approximately
10 bases per turn. (a) Space-filling model of B-DNA showing major
and minor grooves. (b) Diagrammatic representation.

DNA can assume different secondary structures, depending on the
conditions in which it is placed and on its base sequence. B-DNA
is thought to be the most common configuration in the cell.

✔ Concept Check 6
How does Z-DNA differ from B-DNA?

DNA: The Chemical Nature of the Gene

(a) Major information pathways

(b) Special information pathways
DNA

DNA DNA replication
Information is
transferred from DNA
to an RNA molecule.

Transcription

Information is transferred
from one DNA molecule
to another.

RNA
Information is transferred from
RNA to a protein through a
code that specifies the amino
acid sequence.

Reverse
transcription

In some viruses,
information is transferred
from RNA to DNA …

RNA RNA replication

…or to another
RNA molecule.

Translation

PROTEIN
PROTEIN

8.14 Pathways of information transfer within the cell.

Connecting Concepts
Genetic Implications of DNA Structure
Watson and Crick’s great contribution was their elucidation of the
genotype’s chemical structure, making it possible for geneticists to
begin to examine genes directly, instead of looking only at the phenotypic consequences of gene action. The determination of the
structure of DNA led to the birth of molecular genetics—the study
of the chemical and molecular nature of genetic information.
Watson and Crick’s structure did more than just create the
potential for molecular genetic studies; it was an immediate source
of insight into key genetic processes. At the beginning of this chapter, three fundamental properties of the genetic material were identified. First, it must be capable of carrying large amounts of
information; so it must vary in structure. Watson and Crick’s model
suggested that genetic instructions are encoded in the base
sequence, the only variable part of the molecule.
The second necessary property of genetic material is its ability to replicate faithfully. The complementary polynucleotide
strands of DNA make this replication possible. Watson and Crick
proposed that, in replication, the two polynucleotide strands unzip,
breaking the weak hydrogen bonds between the two strands, and
each strand serves as a template on which a new strand is synthesized. The specificity of the base pairing means that only one possible sequence of bases—the complementary sequence—can be
synthesized from each template. Newly replicated doublestranded DNA molecules will therefore be identical with the original double-stranded DNA molecule (see Chapter 9 on DNA
replication).
The third essential property of genetic material is the ability to
translate its instructions into the phenotype. DNA expresses its
genetic instructions by first transferring its information to an RNA
molecule, in a process termed transcription (see Chapter 10). The
term transcription is appropriate because, although the information
is transferred from DNA to RNA, the information remains in the language of nucleic acids. The RNA molecule then transfers the genetic

information to a protein by specifying its amino acid sequence. This
process is termed translation (see Chapter 11) because the information must be translated from the language of nucleotides into
the language of amino acids.
We can now identify three major pathways of information
flow in the cell (Figure 8.14a): in replication, information passes
from one DNA molecule to other DNA molecules; in transcription,
information passes from DNA to RNA; and, in translation, information passes from RNA to protein. This concept of information flow
was formalized by Francis Crick in a concept that he called the
central dogma of molecular biology. The central dogma states
that genetic information passes from DNA to protein in a one-way
information pathway. We now realize, however, that the central
dogma is an oversimplification. In addition to the three general
information pathways of replication, transcription, and translation,
other transfers may take place in certain organisms or under special circumstances, including the transfer of information from RNA
to DNA (in reverse transcription) and the transfer of information
from RNA to RNA (in RNA replication; Figure 8.14b).
Retroviruses (see Chapter 6) and some transposable elements (see
Chapter 13) utilize reverse transcription;. some RNA viruses use
RNA replication.

8.4 Large Amounts of DNA
Are Packed into a Cell
The packaging of tremendous amounts of genetic information into the small space within a cell has been called the ultimate storage problem. Consider the chromosome of the
bacterium E. coli, a single molecule of DNA with approximately 4.6 million base pairs. Stretched out straight, this
DNA would be about 1000 times as long as the cell within
which it resides (Figure 8.15). Human cells contain more
than 6 billion base pairs of DNA, which would measure some

205

206

Chapter 8

E. coli bacterium

Bacterial chromosome

8.15 The DNA in E. coli is about 1000 times
as long as the cell itself.

(a)

1.8 meters stretched end to end. Even DNA in the smallest
human chromosome would stretch 14,000 times the length
of the nucleus. Clearly, DNA molecules must be tightly
packed to fit into such small spaces.
The structure of DNA can be considered at three hierarchical levels: the primary structure of DNA is its nucleotide
sequence; the secondary structure is the double-stranded
helix; and the tertiary structure refers to higher-order folding that allows DNA to be packed into the confined space of
a cell.

Relaxed
circular DNA

A coiled telephone cord is
like relaxed circular DNA.

Concepts
Chromosomal DNA exists in the form of very long molecules, which
must be tightly packed to fit into the small confines of a cell.

One type of DNA tertiary structure is supercoiling,
which takes place when the DNA helix is subjected to strain
by being overwound or underwound. The lowest energy
state for B-DNA is when it has approximately 10 bp per turn
of its helix. In this relaxed state, a stretch of 100 bp of DNA
would assume about 10 complete turns (Figure 8.16a). If
energy is used to add or remove any turns, strain is placed on
the molecule, causing the helix to supercoil, or twist, on itself
(Figure 8.16b and c). Molecules that are overrotated exhibit
positive supercoiling (see Figure 8.16b). Underrotated molecules exhibit negative supercoiling (see Figure 8.16c).
Supercoiling is a partial solution to the cell’s DNA packing
problem because supercoiled DNA occupies less space than
relaxed DNA.
Supercoiling takes place when the strain of overrotating
or underrotating cannot be compensated by the turning of
the ends of the double helix, which is the case if the DNA is
circular—that is, there are no free ends. If the chains can turn
freely, their ends will simply turn as extra rotations are added
or removed, and the molecule will spontaneously revert to
the relaxed state. Both bacterial and eukaryotic DNA usually
folds into loops stabilized by proteins (which prevent free
rotation of the ends), and supercoiling takes place within the
loops.
Supercoiling relies on topoisomerases, enzymes that
add or remove rotations from the DNA helix by temporarily
breaking the nucleotide strands, rotating the ends around
each other, and then rejoining the broken ends. Thus topoisomerases can both induce and relieve supercoiling.
Most DNA found in cells is negatively supercoiled,
which has two advantages over nonsupercoiled DNA. First,
supercoiling makes the separation of the two strands of DNA
easier during replication and transcription. Negatively
supercoiled DNA is underrotated; so separation of the two

(b)

Add two turns
(overrotate)

Positive
supercoil
Positive supercoiling
occurs when DNA
is overrotated; the
helix twists on itself.

(c)

Remove two turns
(underrotate)

Negative
supercoil
Negative supercoiling
occurs when DNA is
underrotated; the
helix twists on itself in
the opposite direction.

If you turn the
receiver when you
hang up, you induce
a negative supercoil
in the cord.

8.16 Supercoiled DNA is overwound or underwound,
causing it to twist on itself. Electron micrographs are
of relaxed DNA (top) and supercoiled DNA (bottom).
[Dr. Gopal Murti/Phototake.]