NUCLEIC ACIDS

The Genetic Material

VARIATIONS
http://www.earthisland.org/eijournal/summer2013/images/larger/kirkland/Collection.jpg
 British Isles
North America
Europe
Western Asia
Isles North Pacific
Ocean
North Atlantic Canary
Ocean Islands
Cape Verde Africa Phillippine
Indian Islands
Marquesas Ocean Keeling
South
America Islands Equator
Galápagos Madagascar
Bahia
Islands Ascension
Society Mauritius Friendly
Islands Bourbon Island Australia Islands
Valparaiso St. Helena
Rio de Janeiro Sydney
Montevideo Cape of King George’s
Buenos Aires Good Hope Sound
Port Desire Hobart New
Falkland South Atlantic Zealand
Straits of Magellan Islands Ocean
Cape Horn Tierra del Fuego

FIGURE 1.6
The five-year voyage of H.M.S. Beagle. Most of the time was spent exploring the coasts and coastal islands of South America,

THE JOURNEY’S
such as the Galápagos Islands. Darwin’s studies of the animals of the Galápagos Islands played a key role in his eventual
development of the theory of evolution by means of natural selection.

FIGURE 1.7
 CHARLES DARWIN
eory of evolution illustrates how science works.

of

on explains
ms on earth
d acquired a
This famous
mple of how
othesis and
ws and wins

(1809–1882;
h naturalist
y and obser-
most famous
l time. This
ies by Means
Preservation
ggle for Life,
it was pub-
in expressed
role in the
hought ever

people be-
ds of organ-
ructures re-
the Creator
e still believe
e thought to
changeable,
urse of time.
a number of
esented the
must have
y of life on
concept he
a coherent,
process, and
de public at-
le indicates,
hat differed FIGURE 1.5
wisdom. Al- Charles Darwin. This newly rediscovered photograph taken in 1881, the year before
hallenge the Darwin died, appears to be the last ever taken of the great biologist.
tor, Darwin

d not simply
them forev-
rwin’s God
the operation of natural laws
r time, or evolution. These
with most people of his time,
rpretation of the Bible and ac-
nd constant world. His revolu-
ALFRED WALLACE
tionary theory deeply troubled not only many of his con-
temporaries but Darwin himself.
The story of Darwin and his theory begins in 1831, when
he was 22 years old. On the recommendation of one of his
professors at Cambridge University, he was selected to serve
D x d

GREGOR MENDEL
Inheritance of Traits
enetic material?
Nucleaus
periment: Cells A. crenulata A. mediterranea

ormation in the

one can ask about heredi-

red in the cell. To answer
Joachim Hammerling,
te for Marine Biology in
pieces and observed the
express hereditary infor-
ammerling needed cells
niently and differentiated
He chose the unicellular
grows up to 5 cm, as a
igations. Just as Mendel
ed fruit flies as model or-
organism that was suited
ion he wanted to answer,
could then be applied to
Nucleus in base determines
bularia have distinct foot, type of cap regenerated
erentiated parts of a sin-
n the foot. As a prelimi-

INFORMATION
amputated the caps of FIGURE 14.2
Hammerling’s Acetabularia reciprocal graft experiment.
He found that when he
Hammerling grafted a stalk of each species of Acetabularia onto
egenerated from the re-
the foot of the other species. In each case, the cap that eventually
ot and stalk). When he
o new foot regenerated by the stalk.
Joachim Hammerling
developed was dictated by the nucleus-containing foot rather than

ling, therefore, hypothe-

 Nucleic Acid

White Blood Cells

Nuclein
Nitrogen & Phosphorus
NO Sulfur

University of Tubingen

CHEMICAL NATURE
Freidrich Meischer
Miescher, Friedrich (1871). "Ueber die chemische Zusammensetzung der
Eiterzellen". Medicinisch-chemische Untersuchungen 4: 441–460.
 Base
P.A. Levene

A T G C
Polymer
Sugar
“Chargaff Rules”
- Erwin Chargaff
(G)

1. Base Composition is NOT the Same

2. A = T ; G = C

THE CHEMICAL NATURE Chemical Specificity of Nucleic Acids and Mechanism of

Their Enzymatic Degradation. Experientia (1950) 6: 206.
 CA =TG

ypes
AT
e ones.

’, on

THE CODE
 Transitions
Transversions

Transversions Transitions

MUTATIONS
 AT

CA
=T
CA =TG G
CA =TG

ypes
AT
AT
e ones.
es.
CA =TG
CA =TG
’, on

pes
types AT
THE CODE
e ones.
AT

ue ones.
’, on
3’, on
d.
 The bad cat saw the big dog and ran and bit him

Insertion - frame shift

The bad cat sai nse rte ddn awt heb igd oga ndr ana ndb ith im

Insertion - inframe
The bad mad cat saw the big dog and ran and bit him

Deletion - inframe
The bad and ran and bit him

Deletion - frame shift

The bad cat sgd oga ndr ana ndb ith im

TYPES
 The bad cat saw the big dog and ran and bit him

Silent
The bad cat saw the big dog and ran and bit him

Mis-Sense
The bad cat sAw the big dog and ran and bit him

Mis-Sense
The bad cat sew the big dog and ran and bit him

Non-Sense
The bad cat s .w the big dog and ran and bit him

TYPES
 Induced Mutations

• Tobacco Smoke

• Ultra-violet Rays

• Nitrous acid

• Intercalating Agents (bind between adjacent bases)

CAUSES
Replication Independent Mutations
Tautomers - Mismatch

CAUSES
 Transition

G G A
+
G C T
T

C
G G G
+
C C C
 Replication Independent Mutations
Deamination of Cytosine & 5m-Cytosine
Replication Independent Mutations
Oxidative Damage
Replication Induced Mutations

SPONTANEOUS
 cultures.

Adaptive

Directed
OR

Selection
Adaptive

Passive
Pre-

OR

MUTATIONS ARE PRE-ADAPTIVE

Figure 1: Luria-Delbruck fluctuation experiment schematic.

Salvador Luria & Max Delbrück

SE Luria and M Delbrück. 1943. Genetics, 28 (491)
 Individual Cultures Samples from Bulk Cultures
Culture Number of Colonies Sample Number of Colonies
Number Resistant to T1 phage Number Resistant to T1 phage

1 1 1 14
2 0
3 3 2 15
4 0
5 0 3 13
6 5
7 0 4 21
8 5
5 15
9 0
10 6
6 14
11 107
12 0 7 26
13 0
14 0 8 16
15 1
16 0 9 20
17 0
18 64 10 13
19 0
Mean 16.7
20 35
Mean 11.4
Variance 18.2
Variance 752.1

SE Luria and M Delbrück. 1943. Genetics, 28 (491)

REPLICA TECHNIQUE
Esther Lederberg & Joshua Lederberg
E Lederberg and J Lederberg. 1952. J. Bacteriol, 63 (3)
Resistant Colonies
Pre-existed
 Live

Small & Rough Live

Heat Killed

Large & Smooth

Live

Heat Killed

DNA ?
Frederick Griffith, 1928
THE GENETIC MATERIAL
Transforming Principle
The Significance of Pneumococcal Types. Journal of Hygiene (1928), 27: 113-159
 DNA / RNA / PROTEIN
Refinement & Elimination
Chloroform extraction - Remove Proteins
Trypsin & Chymotrypsin

Enzymatic digestion - Remove Polysaccharide

Oswald Avery
Ethanol extraction - fibrous precipitate

RNase

X
Enzyme (DNase?)
Colin MacLeod
Chemical Analysis
N:P ~ 1.67; DNA +ve, Protein -ve, RNA -ve
DNA
UV Abs - 260 nm
Genetic Material
Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of
Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III. (1944) J. Exp. Med. 79:
Maclyn McCarty 137–158.
 A FINAL BLOW
Protein- 35S 32P -DNA

No Radioactivity- 35S 32P -Radioactivity

Martha Chase & Alfred Hershey

“This protein probably has no function in the
growth of intracellular phage. The DNA has some
function. Further chemical inferences should not
be drawn from the experiments presented.”

“The chemical identification of the genetic part must wait, however,....”

Independent functions of viral protein and nucleic acid in growth of
bacteriophage. J. Gen. Physiol. (1952) 36: 39–56.
 Base

“Chargaff Rules”
- Erwin Chargaff

1. Base Composition is NOT the Same

Sugar 2. A = T ; G = C

(G)

THE CHEMICAL NATURE Chemical Specificity of Nucleic Acids and Mechanism of

Their Enzymatic Degradation. Experientia (1950) 6: 206.
 PHOTOGRAPH 51

Rosalind Franklin
Base Pair

Major Grove
G=C
34Aº

Molecular Structure of Nucleic Acids A Structure for

Deoxyribose Nucleic Acid. Nature (1953) 171: 737-738.

A =T Molecular Structure of Deoxypentose Nucleic Acid.

Nature (1953) 171: 738-740.

Molecular Configuration in Sodium Thymonucleate.

20Aº Nature (1953) 171: 740-741.

THE SWEET MOMENT

James Dewey Watson & Francis Harry Compton Crick
Maurice Wilkins & Rosalind Franklin
“It has not escaped our notice that the specific pairing we have
postulated immediately suggests a possible copying mechanism for the
genetic material.”

THE HIDDEN EDEN

Mechanism for Replication - Propagation of Life
 CA =TG

AT

READING THE SEQUENCE

e ones.

ALWAYS READ 5’ TO 3’
’, on
ypes

Whichever strand
 • Helices • Loops
A-DNA/RNA:
• Right-handed like B-DNA
• More compact and larger • Stem loop
diameter
• Base pairs not perpendicular
to helix axis
• DNA-RNA hybrid
• Double-stranded RNA

Z-DNA/RNA: • Pseudoknots

37Å
• Transient, not easy to study

34Å
28Å

• Left-handed
• Major & minor grooves of
similar width
• Repeats every 2 bp
• Especially poly(dGC)2
• Correlates with active
26Å 20Å 18Å
transcription
11 10.5 12 base pair / turn

Nucleic acid secondary structures

A C

Packed into
Nucleosome

Telomeric ends
Supercoiling

Never the perfect B-form

 Hoogsteen Base pairing
T=A T H 3
C

3HC
N
O O

H H N
O
N N N H
H
N
Watson-Crick Base pairing O N
eg: Triplex (tRNA)
CH3
and Quadruplex
O N N structures
H H
(telomere)
N N N
H
N
N O

N N

Variation in Base Pairing

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