DNA: The Molecule of

Heredity

Chapter 11

Rosalind Franklin:

A Female Scientist Ahead of her

Time

• When we talk about Watson and Crick, Rosalind Franklin provided crucial X-ray diffraction photos that allowed Watson and Crick to develop the DNA model.

• Why did Rosalind Franklin not get a Nobel Prize?

X-ray Diffraction Studies of

DNA

Fig. 11-4

DNA X-Ray Diffraction Photo by

Rosalind Franklin

DNA Structure

Miescher Discovered DNA

• 1868

• Johann Miescher investigated the chemical

composition of the nucleus

• Isolated an organic acid that was high in

phosphorus

• He called it nuclein

• We call it DNA (deoxyribonucleic acid)

The Discovery of DNA

Fig. E11-3

Griffith Discovers

Transformation

• 1928

• Attempting to develop a vaccine

• Isolated two strains of Streptococcus

pneumoniae

– Rough strain was harmless

– Smooth strain was pathogenic

Griffith Discovers

Transformation

1 Mice injected with

live cells of harmless

strain R.

2 Mice injected with live

cells of killer strain S.

3 Mice injected with

heat-killed S cells.

4 Mice injected with

live R cells plus heat-

killed S cells.

Mice die. Live S cells in

their blood.

Mice live. No live R

cells in their blood.

Mice die. Live S cells in

their blood.

Mice live. No live S cells

in their blood.

Transformation in Bacteria Mouse remains

healthy

Mouse remains

healthy

Mouse contracts

pneumonia and

dies

Living

R-strain

Living

S-strain

Heat-killed

S-strain

Mixture of living R-strain and heat-killed S-strain

Mouse contracts

pneumonia and

dies

(a)

(b)

(c)

(d)

Bacterial strain(s) injected into mouse Results Conclusions

R-strain does

not cause

pneumonia.

S-strain causes

pneumonia.

Heat-killed S-

strain does not

cause pneumonia.

A substance from heat-killed S-strain

can transform the

harmless R-strain

into a deadly

S-strain.

Fig. 11-1

Transformation

• What happened in the fourth

experiment?

• The harmless R cells had been

transformed by material from the dead

S cells

• Descendents of the transformed cells

were also pathogenic

Mystery of the

Hereditary Material

• Originally believed to be an unknown

class of proteins

• Thinking was

– Heritable traits are diverse

– Molecules encoding traits must be diverse

– Proteins are made of 20 amino acids and

are structurally diverse

Oswald & Avery

• What is the transforming material?

• Cell extracts treated with protein-

digesting enzymes could still transform

bacteria

• Cell extracts treated with DNA-digesting

enzymes lost their transforming ability

• Concluded that DNA, not protein,

transforms bacteria

Bacteriophages

• Viruses that infect

bacteria

• Consist of protein

and DNA

• Inject their

hereditary material

into bacteria

Hershey & Chase’s

Experiments

• Created labeled bacteriophages

– Radioactive sulfur

– Radioactive phosphorus

• Allowed labeled viruses to infect

bacteria

• Asked: Where are the radioactive labels

after infection?

Hershey and Chase Results

virus particle

labeled with 35S

DNA (blue)

being injected

into bacterium

35S remains

outside cells

virus particle

labeled with 32P

DNA (blue)

being injected

into bacterium

35P remains

inside cells

Structure of the

Hereditary Material

• Experiments in the 1950s showed that DNA is the hereditary material

• Scientists raced to determine the structure of DNA

• 1953 - Watson and Crick proposed that DNA is a double helix

Structure of Nucleotides

in DNA

• Each nucleotide consists of

– Deoxyribose (5-carbon sugar)

– Phosphate group

– A nitrogen-containing base

• Four bases

– Adenine, Guanine, Thymine, Cytosine

Nucleotide Bases

sugar

(deoxyribose)

adenine

A

base with a

double-ring

structure

guanine

(G)

base with a

double-ring

structure

cytosine

(C)

base with a

single-ring

structure

thymine

(T)

base with a

single-ring

structure

Composition of DNA

• Chargaff showed:

– Amount of adenine relative to guanine

differs among species

– Amount of adenine always equals amount

of thymine and amount of guanine always

equals amount of cytosine

A=T and G=C

Watson-Crick Model

• DNA consists of two nucleotide strands

• Strands run in opposite directions

• Strands are held together by hydrogen bonds

between bases

• A binds with T and C with G

• Molecule is a double helix

Watson-Crick

Model

Patterns of Base Pairing

Rosalind Franklin’s Work

• Was an expert in x-ray crystallography

• Used this technique to examine DNA

fibers

• Concluded that DNA was some sort of

helix

DNA Structure Helps

Explain How It Duplicates

• DNA is two nucleotide strands held

together by hydrogen bonds

• Hydrogen bonds between two strands

are easily broken

• Each single strand then serves as

template for new strand

DNA

Replication

new new old old

• Each parent

strand remains

intact

• Every DNA

molecule is half

“old” and half

“new”

Base Pairing

during

Replication

Each old strand

serves as the template

for complementary

new strand

Two identical DNA

double helices, each

with one parental

strand (blue) and

one new strand (red)

One DNA

double helix

DNA replication

Semiconservative Replication

of DNA

Fig. 11-7

A Closer Look at

Strand Assembly

Energy for strand

assembly is

provided by

removal of two

phosphate groups

from free

nucleotides

newly

forming

DNA

strand

one parent

DNA strand

Continuous and Discontinuous

Assembly

Strands can

only be

assembled in

the 5’ to 3’

direction

Enzymes in Replication

• Enzymes unwind the two strands

• DNA polymerase attaches

complementary nucleotides

• DNA ligase fills in gaps

• Enzymes wind two strands together

DNA Repair

• Mistakes can occur during replication

• DNA polymerase can read correct

sequence from complementary strand

and, together with DNA ligase, can

repair mistakes in incorrect strand

What about Cloning?

Moral Dilemma or Technological

Revolution

• Making a genetically identical copy of

an individual

• Researchers have been creating clones

for decades

• These clones were created by embryo

splitting

• Showed that differentiated cells could

be used to create clones

• Sheep udder cell was combined with

enucleated egg cell

• Dolly is genetically identical to the

sheep that donated the udder cell

Dolly:

Cloned from an Adult Cell

More Clones

• Mice

• Cows

• Pigs

• Goats

• Guar (endangered species)

How Do Mutations Occur?

• Mistakes do happen

– DNA is altered or damaged in a number of

ways

• Mistakes are made during normal DNA

replication

• Certain chemicals (some components of

cigarette smoke, for example) increase DNA

errors during and after replication

• Ultraviolet radiation or X-rays also contribute to

incorrect base pairing

Mutations

Fig. 11-8a

Mutations

Fig. 11-8b

Mutations

Fig. 11-8c

Mutations

Fig. 11-8d

11.5 How Do Mutations

Occur?

• Mutations may have varying effects on

function

– Mutations are often harmful, and an

organism inheriting them may quickly die

– Some mutations may have no functional

effect

– Some mutations may be beneficial and

provide an advantage to the organism in

certain environments