The document discusses the history and structure of nucleic acids. It describes how Friedrich Miescher first isolated nuclein in 1869 and how the tetranucleotide hypothesis proposed nucleic acids contained one of each nucleotide connected by phosphodiester linkages. Later, Avery, MacLeod and McCarty showed DNA could transform cells, supporting it as the molecule of heredity. Watson and Crick finally determined DNA's double helix structure in 1953. There are two main types of nucleic acids, DNA and RNA, which have similar structures but RNA contains uracil instead of thymine and has a 2' hydroxyl group.

1. NUCLEIC
ACIDS

2. Topic Outline:
 History of Nucleic Acids
 Structure and Function
 Types of Nucleic Acids
1. DNA
2. RNA
 Central Dogma of Life

3. Friedrich Miescher in
1869
 isolated what he called nuclein from the
nuclei of pus cells

4. Richard Altmann in 1889
 Nuclein was shown to have acidic
properties, hence it became called nucleic
acid

5. 1920s
 the tetranucleotide hypothesis was
introduced

6. The Tetranucleotide
hypothesis
 Up to 1940 researchers were convinced
that hydrolysis of nucleic acids yielded the
four bases in equal amounts.
 Nucleic acid was postulated to contain
one of each of the four nucleotides, the
tetranucleotide hypothesis.
 Takahashi (1932) proposed a structure of
nucleotide bases connected by
phosphodiester linkages.

7. The Tetranucleotide
hypothesis
adenine phosphate uracil
pentose
pentose
phosphate
phosphate
pentose pentose
cytosine phosphate guanine

8. Astbury and Bell in 1938
 First X-ray diffraction pattern of DNA is
published.
 The pattern indicates a helical
structure, indicated periodicity.

9. X-ray diffraction of DNA

10. Wilkins & Franklin (1952): X-ray
crystallography

11. Avery, MacLeod, and Mc
Carty in 1944
 demonstrate DNA could “transform”
cells.
 Supporters of the tetranucleotide
hypothesis did not believe nucleic acid
was variable enough to be a molecule
of heredity and store genetic
information.

12. The Avery, MacLeod, and
McCarty Experiment
Mice injected with virulent bacteria die

13. The Avery, MacLeod, and McCarty
Experiment
Mice injected with nonvirulent bacteria live

14. The Avery, MacLeod, and McCarty Experiment
Mice injected with heat-killed virulent bacteria live

15. The Avery, MacLeod, and McCarty
Experiment
Mice injected with a mixture of nonvirulent bacteria
and heat-killed virulent bacteria die

16. The Avery, MacLeod, and McCarty
Experiment
Mice injected with a mixture of nonvirulent bacteria
and DNA from heat-killed virulent bacteria die

17. Erwin Chargaff in late
1940s
 used paper chromatography for
separation of DNA hydrolysates.
 Amount of adenine is equal to amount
of thymine and amount of guanine is
equal to amount of cytosine.

18. Hershey and Chase in
1952
 confirm DNA is a molecule of heredity.

19. The Hershey-Chase Experiment

20. The Hershey-Chase Experiment

21. Watson and Crick in 1953
 determine the structure of DNA

22. Watson & Crick Base pairing

23. Francis Crick in 1958
 proposes the “central dogma of molecular biology” .
 Kornberg purifies DNA polymerase I

24. 1969
 Entire genetic code determined

25. Important Developments
 1972 – First recombinant DNA molecule
constructed Lambda phage DNA
inserted into SV40 virus
- Restriction enzyme EcoRI used to
create a recombinant plasmid
containing penicillin and
tetracycline resistance
 1982 – Tetrahymena ribosomal RNA
splicing shown to be self- splicing

26. Important Developments
 1986 – RNA is shown to act as an enzyme
- The polymerase chain reaction
(PCR) was developed by
Kari Mullis at Cetus Corporation.
 1995 – First complete genome
sequenced of the bacterium
Haemophilus influenzae at TIGR
 2001 – Human genome sequenced by
NIH and Celera Genomics

27. Nucleic Acids
• Nucleic Acids are very long, thread-like
polymers, made up of a linear array of monomers
called nucleotides.
• Nucleic acids vary in size in nature
• tRNA molecules contain as few as 80 nucleotides
• Eukaryotic chromosomes contain as many as
100,000,000 nucleotides.

28. Two types of nucleic acid
are found
 Deoxyribonucleic acid (DNA)
 Ribonucleic acid (RNA)

29. DNA and RNA
DNA
deoxyribonucleic acid
nucleic acid that stores genetic information
found in the nucleus of a mammalian cell.
RNA
ribonucleic acid
3 types of RNA in a cell
Ribosomal RNAs (rRNA) are components of ribosomes
Messenger RNAs (mRNA) carry genetic information
Transfer RNAs (tRNA) are adapter molecules in translation

30. The distribution of nucleic
acids in the eukaryotic
cell is found in the nucleus
 DNA
with small amounts in mitochondria and
chloroplasts
 RNA is found throughout the cell

31. The nucleus contains the cell’s DNA
(genome)
Nucleus

32. RNA is synthesized in the nucleus
and
exported to the cytoplasm
Nucleus
Cytoplasm

33. Deoxyribonucleotides found
in DNA
dA dG dT dC

34. Ribonucleotides found in
RNA
A G U C

35. DNA as genetic material:
The circumstantial evidence
1. Present in all cells and virtually restricted to the nucleus
2. The amount of DNA in somatic cells (body cells) of any
given species is constant (like the number of
chromosomes)
3. The DNA content of gametes (sex cells) is half that of
somatic cells.
In cases of polyploidy (multiple sets of chromosomes)
the DNA content increases by a proportional factor
4. The mutagenic effect of UV light peaks at 253.7nm. The
peak for the absorption of UV light by DNA

36. NUCLEIC ACID STRUCTURE
 Nucleic acids are polynucleotides
 Their building blocks are nucleotides

37. NUCLEOTIDE STRUCTURE
PHOSPATE SUGAR BASE
Ribose or PURINES PYRIMIDINES
Deoxyribose
Adenine (A) Cytocine (C)
Guanine(G) Thymine (T)
Uracil (U)
NUCLEOTIDE

38. Nucleotide Structure
All nucleotides contain three components:
1. A nitrogen heterocyclic base
2. A pentose sugar
3. A phosphate residue

39. Ribose is a pentose
C5
O
C4 C1
C3 C2

40. Spot the difference
RIBOSE DEOXYRIBOSE
CH2OH CH2OH
O OH O OH
C C C C
H H H H H H H H
C C C C
OH OH OH H

41. Chemical Structure of DNA vs RNA
Ribonucleotides have a 2’-OH
Deoxyribonucleotides have a 2’-H

42. P
THE SUGAR-PHOSPHATE
BACKBONE P
 The nucleotides are all
orientated in the same P
direction
 The phosphate group joins the P
3rd Carbon of one sugar to the
5th Carbon of the next in line. P
P

43. P
G
ADDING IN THE BASES
P
C
 The bases are
P
attached to the 1
st
C
Carbon
 Their order is P
important A
It determines the P
genetic information of T
the molecule
P
T

44. Hydrogen bonds
DNA IS MADE OF P
G
TWO STRANDS OF C
P
POLYNUCLEOTIDE P
C G
P
P
C G
P
P
A T
P
P
T A
P
P
T A
P

45. DNA IS MADE OF TWO STRANDS OF
POLYNUCLEOTIDE
 The sister strands of the DNA molecule run in opposite
directions (antiparallel)
 They are joined by the bases
 Each base is paired with a specific partner:
A is always paired with T
G is always paired with C
“Purine with Pyrimidine”
 The sister strands are complementary but not identical
 The bases are joined by hydrogen bonds, individually
weak but collectively strong
 There are 10 base pairs per turn

47. Purines & Pyrimidines
Structure of Nucleotide
Bases

48. 5’ End
Nucleotides
are
linked by
phosphodies
ter
bonds
3’ End

49. Three-dimensional structure of B
DNA
NMR solution structure of a 12 nucleotide fragment of DNA
5’- C G C G A A T T C G C G –3’
3’- G C G C T T A A G C G C –5’
Total of 32 hydrogen bonds.
Reading Assignment:
Tjandra et al
Journal of the American Chemical Society (2000) 122, 6190

50. Cellular Processes
replication
DNA
transcription
RNA (mRNA)
translation
Proteins

51. RNA and Transcription
DNA is in the nucleus
Proteins are synthesized on ribosomes in the
cytoplasm
RNA carries the genetic information from the
nucleus to the cytoplasm
This RNA is called messenger RNA (mRNA)

52. RNA Structure
Transcription of a DNA molecule results in a mRNA
molecule that is single-stranded.
RNA molecules do not have a regular structure like DNA.
The structures of RNA molecules are complex and unique.
RNA molecules can base pair with complementary DNA
or RNA sequences.
G pairs with C, A pairs with U, and G pairs with U.

53. RNA structures have many
hairpins and loops

54. Structure of RNA Hairpin