Chap 4

Nucleic Acids and the RNA World

Ki-Young Kim
kiyoung@khu.ac.kr
국경대 324호

Roadmap 4
In this chapter you will learn that
Nucleic acids store the information that encodes life

by asking
What is a nucleic acid?
4.1
comparing/contrasting
and by asking
DNA RNA Could life have
structure and structure and evolved from
function function an RNA?
4.2 4.3 4.4
specialized for
Stability and Versatility and
storage catalysis
What Is a Nucleic Acid?
• A nucleic acid is a polymer of nucleotide monomers

• Three components of a nucleotide:

1. A phosphate group
2. A five-carbon sugar
3. A nitrogenous (nitrogen-containing) base

• The phosphate is bonded to the sugar molecule

- In turn, the sugar molecule is bonded to the nitrogenous base

What Is a Nucleic Acid?

• Ribonucleotides
- The sugar is ribose
• Deoxyribonucleotides
- The sugar is deoxyribose (deoxy means lacking oxygen)

• These two sugars differ by a single oxygen atom

- Ribose has an: OH group bonded to the 2′ carbon
- Deoxyribose has an H instead at the same location

• In both of these sugars

- An –OH group is bonded to the 3′ carbon
What Is a Nucleic Acid?
• There are two groups of nitrogenous bases:
1. Purines
- Adenine
- Guanine
2. Pyrimidines
- Cytosine
- Uracil
- Thymine

• The base uracil (U) is found only in ribonucleotides

• The base thymine (T) is found only in deoxyribonucleotides

Figure 4.1 The General Structure of a Nucleotide.

(a) Nucleotide (c) Nitrogenous bases

Phosphate group is bonded
to 5 carbon of sugar

Nitrogenous
base

Phosphate Cytosine (C) Uracil (U) in RNA Thymine (T) in DNA

group Nitrogenous
5-carbon base is bonded to
1 carbon of sugar Pyrimidines
sugar

(b) Sugars
Purines are
larger than
pyrimidines

Guanine (G) Adenine (A)

Ribose in RNA Deoxyribose in DNA Purines

Could Chemical Evolution Produce
Nucleotides?
• Simulations of chemical evolution
- Have not yet produced nucleotides
- Sugars and purines are easily made
- Pyrimidines and ribose are not easily synthesized

• Ribose problem
- Ribose must have been dominant on ancient Earth
- For nucleic acids to form

Could Chemical Evolution Produce

Nucleotides?
• Conditions that exist in deep-sea hydrothermal vent systems may point
to a possible solution

• Simulate the conditions that exist in these vents

- Then test whether minerals that are predicted to have existed in the vent
chimneys are able to bind sugars

• What researchers found was striking

- The minerals preferentially bound to ribose over other pentoses and hexoses
Organic Chemistry on Early Earth
• Deep-sea vents
- Extremely hot
- Gases such as CO2 and H2
• Reactive metals such as nickel and iron (may have been present)

The structure and classification of some

monosaccharides
Aldose (Aldehyde Sugar) Ketose (Ketone Sugar)
Pentoses: 5-carbon sugars (C5H10O5)

Ribose Ribulose
The structure and classification of some
monosaccharides
Aldose (Aldehyde Sugar) Ketose (Ketone Sugar)
Hexoses: 6-carbon sugars (C6H12O6)

Glucose Galactose Fructose

Structure of monosaccharides
1 6
6
2 5 5

3
4 1
1 4
4
3 2 3 2
5

5 5
Linear and ring forms HOH2C HOH2C
O O
4 C C 1 4 C C 1

OH OH
C3 C2 C3 C2

OH OH OH H
Ribose Deoxyribose
Nucleotides Polymerize to Form Nucleic
Acids
• Nucleic acids form when nucleotides polymerize
• Phosphodiester linkage (bond) occurs between
- The phosphate group on the 5′ carbon of one nucleotide
- And the –OH group on the 3′ carbon of another
• Forms through condensation reaction
• Two types of nucleotides are involved
1. Ribonucleotides
• Contain the sugar ribose and form RNA
2. Deoxyribonucleotides
• Contain the sugar deoxyribose and form DNA

Figure 4.2 Nucleotides Polymerize via Phosphodiester Linkages.

5 5

3 3
Condensation
reaction

Phosphodiester
linkage

5 5

3 3
The Sugar-Phosphate Backbone Is
Directional
• The sugar-phosphate backbone of a nucleic acid is directional
(has polarity)
- One end has an unlinked 5′ carbon
- The other end has an unlinked 3′ carbon

• The nucleotide sequence is written in the 5′ → 3′ direction

- Reflects the order that nucleotides are added to a growing molecule
- The nucleic acid’s primary structure is the nucleotide sequence

The Sugar-Phosphate Backbone Is

Directional
• In a single strand of RNA or DNA
- One end has an unlinked 5′ phosphate
- The other end has an unlinked 3′ hydroxyl
 The sugar-phosphate
Figure 4.3 RNA Has a backbone of RNA
5 end of 5
Sugar-Phosphate Backbone. nucleic acid

5

3

5

3

5

3

3 and 5 carbons joined by

phosphodiester linkage
5

3
3 end of nucleic acid:
new nucleotides are added 3
to the unlinked 3 hydroxyl

The Polymerization of Nucleic Acids Is

Endergonic
• Polymerization of nucleic acids is
- An endergonic process
- Catalyzed by enzymes
• Energy for polymerization comes from
- The phosphorylation of the nucleotides
• Phosphorylation
- Is the transfer of a phosphate group(s) to a substrate molecule
- Raises the potential energy of the substrate
- Enables endergonic reactions
The Polymerization of Nucleic Acids Is
Endergonic
• Nucleoside triphosphate
- Two phosphates are transferred
- Created during nucleic acid polymerization
• Figure 4.4a shows an example of an activated nucleotide
• This molecule is called adenosine triphosphate, or ATP

Figure 4.4 Activated Monomers Drive Polymerization Reactions.

(a) ATP is an example of an activated nucleotide.

5

Adenine

The addition of phosphate

3
groups raises the potential
energy of the monomer
Ribose

(b) Energy is released when phosphates are removed by hydrolysis.

Inorganic Energy used to link

Water AMP pyrophosphate nucleotide to RNA
What Is the Nature of DNA’s Secondary
Structure?
• Chemists
- Had worked out the structure of nucleotides
- Knew that DNA polymerized through the formation of phosphodiester linkages

• Watson and Crick knew that the molecule had a sugar-phosphate

backbone

What Is the Nature of DNA’s Secondary

Structure?
• Erwin Chargaff established two empirical rules for DNA:
1. The total number of purines and pyrimidines is the same
2. The numbers of A’s and T’s are equal and the numbers of C’s and G’s are equal
Variation in DNA between Organisms
• Ratios of G to C and A to T are fixed in any specific
organism

• The total percentage of G + C varies over a range of

22 to 73%

• These reflect differences in physical properties

What Is the Nature of DNA’s Secondary

Structure?
• Rosalind Franklin and Maurice Wilkins calculated the distances
between groups of atoms in the DNA molecule

• By bombarding DNA with X-rays and analyzing how it scattered the

radiation
- Called X-ray crystallography
 Rosalind Franklin and her X-ray diffraction photo of DNA.

(a) Rosalind Franklin (b) Franklin’s X-ray diffraction

photograph of DNA

What Is the Nature of DNA’s Secondary

Structure?
• The scattering patterns showed that the distances were repeated many
times
- Inferred that DNA molecules had a regular and repeating structure
• The pattern of X-ray scattering suggested that the molecule was
helical, or spiral, in nature
Watson and Crick’s Model of DNA’s
Secondary Structure
• James Watson and Francis Crick determined
1. DNA strands run in an antiparallel configuration
2. DNA strands form a double helix
- The hydrophilic sugar-phosphate backbone faces the exterior
- Nitrogenous base pairs face the interior

Watson and Crick’s Model of DNA’s

Secondary Structure
3. Purines always pair with pyrimidines
- Strands form complementary base pairs A-T and G-C
• A-T have two hydrogen bonds
• C-G have three hydrogen bonds

4. DNA has two different-sized grooves:

- The major groove
- The minor groove
Figure 4.6 Complementary Base Pairing Is Based on Hydrogen Bonding.

(a) Only purine-pyrimidine pairs fit inside the (b) Hydrogen bonds form between G-C pairs and
double helix. A-T pairs.
5 Guanine Cytosine 3
Antiparallel
Purine-purine pair strands
NOT ENOUGH SPACE

Sugar-phosphate backbone
Pyrimidine-pyrimidine pair
TOO MUCH SPACE

Purine-pyrimidine pair Hydrogen

JUST RIGHT Adenine bonds Thymine

Space inside sugar-

phosphate backbones

DNA contains thymine,

3 whereas RNA contains uracil 5

Summary of DNA’s Secondary Structure

• DNA’s secondary structure consists of
- Two antiparallel strands twisted into a double helix

• The molecule is stabilized by

- Hydrophobic interactions in its interior

• By hydrogen bonding between

- The complementary base pairs
- A-T and G-C
 Figure 4.7 The Secondary Structure of DNA Is a Double Helix.
(a) Cartoons of DNA structure (b) Space-filling model of DNA double helix
5 3 5 3 5 3

Major
groove

helix (10 rungs per turn) 3.4 nm

Length of one complete turn of
Minor
groove

Distance
between
bases
0.34 nm

5 3
3 5 5 3
Base pairing Double helix Width of helix
2.0 nm

DNA Contains Biological Information

• DNA can store and transmit biological information

• DNA carries the information required for the organism’s growth and
reproduction

• The language of nucleic acids is contained in the sequence of the

bases

• DNA carries the information required for the growth and reproduction
of all cells
How Does DNA Replicate?
• “It has not escaped our notice that the specific pairing we have
postulated immediately suggests a possible copying mechanism.”
—Watson and Crick
• Here’s the key insight about DNA
- Primary structure serves as a mold or template for the synthesis of a
complementary strand
- Contains the information required for a copy of itself to be made
• Complementary base pairing
- Provides a simple mechanism for DNA replication
- Each strand can serve as a template for the formation of a new complementary
strand

How Does DNA Replicate?

• Step 1
- Heating or enzyme-catalyzed reactions
• Cause the double helix to separate
• Step 2
- Free deoxyribonucleotides form hydrogen bonds with complementary bases
on the original strand of DNA
• Called a template strand
- Sugar-phosphate groups form phosphodiester linkages to:
• Create a new strand
• Called a complementary strand
How Does DNA Replicate?
• Step 3
- Complementary base pairing allows
• Each strand of a DNA double helix to be copied exactly
• Producing two identical daughter molecules

How Does DNA Replicate?

• DNA replication requires two steps:
1. Separation of the double helix
2. Hydrogen bonding of deoxyribonucleotides with complementary bases
- On the original template strand
- Followed by phosphodiester bond formation between the deoxynucleotides to form the
complementary strand
 5 3
Figure 4.8 Making a Copy of DNA.
1. Strand separation

5 3

5 3 5 3

2. Base pairing
with template

3 5 3 5

3 5 3 5
3. Polymerization

The original
molecule has
been copied.
5 3 5 3
New Old Old New

Is DNA a Catalytic Molecule?

• DNA’s stability
- Makes it a reliable store for genetic information
- It is less reactive than RNA
- It is more resistant to chemical degradation

• Stable molecules such as DNA make poor catalysts

• Biologists think that the first life-form was made of RNA
- Not DNA
- DNA does not appear to catalyze any chemical reaction
Is DNA a Catalytic Molecule?
• Orderliness and stability make DNA
- A dependable information repository
- But extraordinarily inept at catalysis

RNA Structure and Function

• RNA (like DNA) has a primary structure consisting of a sugar-
phosphate backbone
- Formed by phosphodiester linkages
- Extending from that backbone, a sequence of four types of nitrogenous bases
• The primary structure of RNA differs from DNA
1. RNA contains uracil instead of thymine
2. RNA contains ribose instead of deoxyribose
- The presence of the –OH group on ribose makes RNA
• Much more reactive
• Less stable than DNA
 RNA’s Secondary Structure
• RNA’s secondary structure results from complementary base pairing

• The bases of RNA typically form hydrogen bonds with

complementary bases on the same strand

• The RNA strand folds over, forming a hairpin structure

- The bases are on one side of the fold
- The bases align with an antiparallel RNA segment on the other side of the fold

Figure 4.9 Complementary

Base Pairing and Secondary
Structure in RNA: Stem- Loop
and-Loop Structures.
Hairpin

Single-stranded
region forms a loop

Double-stranded region
forms a double helix
Stem

3

5

Nitrogenous bases
RNA’s Structure
• RNA molecules can also have tertiary structure
- Forms when secondary structures fold into more complex shapes
• RNA (like DNA) can function as
- An information-containing molecule
- Capable of self-replication
• Structurally/chemically, RNA is intermediate between
- The complexity of proteins
- The simplicity of DNA

Summary Table 4.1 DNA and RNA Structure

RNA and Self-Replication
• Step 1
- A complementary copy of the RNA is made
- Free ribonucleotides form hydrogen bonds with complementary bases on the original template
strand of RNA

• Step 2
- Their sugar-phosphate groups form phosphodiester linkages to produce a double-stranded RNA
molecule

• Step 3
- The hydrogen bonds between the double-stranded product must be broken by heating or by a
catalyzed reaction

RNA’s Versatility
• The newly made complementary RNA molecule now exists
independently of the original template strand

• If steps 1–3 were repeated with the new strand serving as a template
(steps 4–6)
- Then the resulting molecule would be a copy of the original
Figure 4.10 RNA Molecules Contain Information That Allows Them to Be Replicated.

3
3 5
3 5 5
5 3

1. Complementary 4. Copy serves as new

bases pair. template.
5 3 3
3 5
5

Template strand 3 New copy strand 5

3 5
2. Copied strand 5. New copy polymerizes.
polymerizes. 5 3

Copied strand 3 New template strand

5

5 5

3 3

3. Copy and template 6. New copy is identical to

separate. original template.
5 5

3 3

RNA’s Versatility
• RNA can function as a catalytic molecule
- Ribozymes are enzyme-like RNAs

• RNA has a degree of structural and chemical complexity

- It is capable of catalyzing a number of chemical reactions

leadzyme, hammerhead ribozyme, twister ribozyme

Figure 4.11 Tertiary Structure of
the Tetrahymena Ribozyme.

Folding brings
widely spaced
nucleotides
together at the
active site of
this catalytic
RNA

The First Life-Form: RNA

• The theory of chemical evolution
- Life began as a naked self-replicator
- A molecule that existed by itself in solution
- Without being enclosed in a membrane
• To make a copy of itself, the first living molecule had to
- Provide a template that could be copied
- Catalyze polymerization reactions that would link monomers into a copy of that
template
• RNA is capable of both processes
- Most origin-of-life researchers propose that the first life-form was made of RNA
The First Life-Form: RNA
• RNA is not very stable
- But it might have survived long enough in the prebiotic soup to replicate itself
- And so it may have been the first life-form

• RNA replicase is a ribozyme that

- Can catalyze the addition of ribonucleotides to a complementary RNA strand
- Can replicate RNA

End of week 4
• Good luck for your health
• See you next week