Role of the genetic material

1
(No Transcript)
2
Role of the genetic material A genetic
material must carry out two jobs duplicate
itself and control the development of the rest of
the cell in a specific way.
-Francis Crick
3

DNA
Deoxyribonucleic acid The information
necessary to sustain and perpetuate life is found
within a molecule. This is the genetic material
that is passed from one generation to the
next---a blue print for building living organisms.
4
History
Although we now accept the idea that DNA is
responsible for our biological structure, before
the mid-1800s it was unthinkable for the leading
Scientists and Philosophers that a chemical
molecule could hold enough information to build a
human. They believed that plants and animals had
been specifically designed by a creator.
5
History
Charles Darwin is famous for challenging this
view. In 1859 he published The Origin of
Species which expressed that living things
appear to be designed, but may actually be the
result of natural selection. Darwin showed
that living creatures evolve over several
generations through a series of small changes.
6
History
In the 1860s Darwin's ideas were finally
supported when genetics was discovered by Gregor
Mendel. He found that Factors determine the
characteristics a living thing will express. The
genes are passed to later generations, with a
child taking genes from both its parents. The
great mystery was where and how would this
information be stored?
1823-1884 Czech monk
7

• Friedrich Miescher Swiss physician

1844-1895
Search for genetic material In 1870, a
German scientist named Friedrich Miescher had
isolated the chemicals found in the nucleus.
These were proteins and nucleic acids. (His
nuclei came from pus!)
8
History
While Miescher found these nucleic acids
interesting, and spent a great deal of time
studying their chemical composition, he wasnt
alone in believing that proteins were more likely
to be the chemicals involved in inheritance,
because of their immense variability.
Proteins were made up of 20 different building
blocks (amino acids), as opposed to the mere 4
building blocks of nucleic acids.
9
Discovery of a Transforming Principle Frederick
Griffith, in 1928 - Pneumonia (Diplococcus
pneumoniae) infects mice. - Mice develop
pneumonia and die. Two types of bacteria - S
bacteria smooth coat pneumonia - R
bacteria rough coat - no pneumonia Coat type is
associated with virulence.

1881 - 1941

• English army medical officer

10
History
Search for genetic material 1928 Frederick
Griffith transforming principle
11
Frederick Griffiths 1928 Experiment
12
Griffiths experiment identifying the
transforming principle
13
(No Transcript)
14
Discovery of DNA

• The extracts of heat-killed S bacteria cells
• contained protein, RNA and DNA
• Which of these substances were essential for
• transformation?
• How did they figure out which substance was
  essential for transformation?

15


KEY PLAYERS Oswald Avery (1877-1955) Microbiolo
gist Avery led the team that showed that DNA is
the unit of Inheritance. One Nobel laureate has
called the discovery "the historical platform of
modern DNA research", and his work inspired
Watson and Crick to seek DNA's structure.
16
1600s 1800s 1850s 1900s 1950s 2000s

• 1877-1955
• Oswald Avery American bacteriologist
• 1943 proved that DNA carries genes

S
R
DNA
S
17
Discovery of DNA

• They decided to use the process of elimination
• Extracts were treated with either
• Proteases (to destroy protein)
• RNase (to destroy RNA)
• DNase (to destroy DNA)
• Transformation was due exclusively to DNA

18
(No Transcript)
19
History
Search for genetic material
It wasnt until 1944 that Oswald Avery and his
colleagues, who were studying the bacteria which
causes pnuemonia, discovered by process of
elimination that bacteria contain nucleic acids,
and that DNA is the chemical which carries
genes. Despite the conclusive results of
Averys experiments, the theory of nucleic acids
being the genetic material was still not a
popular one, but experiments Performed with
viruses also showed that nucleic acids were the
genetic material and this confirmed Averys work.
20
1600s 1800s 1850s 1900s 1950s 2000s

• Alfred Hershey and Martha Chase 1952
• used bacteriophage (a virus) to prove that
• DNA was the hereditary material
• the bacteriophage was the ideal organism for
  
• settling the debate between protein and
  DNA.

21
What are viruses?

• Viruses are organized associations of
  macromolecules-nucleic acid contained within a
  protective shell of protein units .

A virus is NOT alive. A virus is NOT made out of
a cell.
22
(No Transcript)
23
DNA discovery Hershey-Chase 1952
24
DNA discovery Hershey-Chase 1952
25
History
Search for genetic material 1952 -
Hershey-Chase Experiment
26
Hershey and
27
Hershey and
28
History
Search for genetic material

• Classic experiments for evidence Griffith
  transformation Hershey-Chase DNA necessary
  to produce more virus
• Other supporting evidence DNA volume doubles
  before cells divide Chargaff ratio of
  nucleotides A T and G C

29
1600s 1800s 1850s 1900s 1950s 2000s

• 1929-1992
• Erwin Chargaff Austrian American biochemist
• (1950) Discovered the base-pairing regularities
  or "complementarity relationships" of nucleic
  acids that provided one of the key steps in
  developing a structural model for DNA.

30

KEY PLAYERS Erwin Chargaff (1905-2002)
Chargaff discovered the pairing Rules of DNA
letters, noticing that A Matches to T, and C to
G. He later criticized molecularbiology, the
discipline he helped invent, as "the practice of
biochemistry without a license", and once
described Francis Crick as looking like "a faded
racing tout".

31
1600s 1800s 1850s 1900s 1950s 2000s

• 1953
• James Watson American ornithologist
• Francis Crick British Physicist

32
The Scientists
James Watson was an American, born in 1928, was
only 24 when the discovery was made. He went to
Chicago University at the age of 15. Francis
Crick was born in 1916. He went to London
University and trained as a physicist. After the
war he changed the direction of his research to
molecular biology.

33
KEY PLAYERS James Watson (1928- ) Watson
went to university in Chicago at age 15, and
teamed up with Crick in Cambridge in late
1951. After solving the double helix, he went on
to work on viruses and RNA, another genetic
information carrier. He also helped launch the
human genome project, and is president of Cold
Spring Harbor Laboratory in New York.

34
KEY PLAYERS Francis Crick
(1916-2004)Crick trained and worked as a
physicist, but switched to biology after the
Second World War. After co discovering the
structure of DNA, he went on to crack the genetic
code that translates DNA into protein. At the
time of his death he was studying consciousness
at California's Salk Institute.

35
The Discovery
The DNA molecule was discovered in 1951 by
Francis Crick, James Watson and Maurice Wilkins
using X-ray Diffraction. In Spring 1953,
Francis Crick and James Watson, two scientists
working at the Cavendish Laboratory in Cambridge,
discovered the structure of the DNA a double
helix, or inter-locking pair of spirals, joined
by pairs of molecules.
36
How Did They Do That?
37
The Discovery
The seed that generated this was Watsons
presence at a conference in Naples in 1951, where
an x-ray diffraction picture from DNA was shown
by Maurice Wilkins from Kings College in
London. This made a strong impression on Watson
the first indication that genes might have a
regular structure.
38

KEY PLAYERS Linus Pauling (1901-1994) The
titan of twentieth-century chemistry, Pauling
led the way in working out the structure of big
biological molecules, and Watson and Crick saw
him as their main competitor. In early 1953,
working without the benefit of X-ray pictures, he
published a paper suggesting that DNA was a
triple helix.

39
James Watson shared an office with Crick, and
the topic of DNA structure naturally arose
particularly how to determine it. They were
inclined to follow the methods of Pauling who had
designed a helical structure by building a model
consistent with the x-ray patterns from fibrous
proteins. Like proteins, DNA was built from
similar units the bases adenine(A), thymine(T),
guanine(G) and cytosine(C), and so it seemed
likely that DNA also had a helical structure. The
published x-ray patterns of DNA were not very
clear, so contact was made with Kings.
Watson attended a DNA colloquium there in
November 1951, at which Rosalind Franklin
described her results.
40
1600s 1800s 1850s 1900s 1950s 2000s

• 1920 1958
• Rosalind Franklin- English Chemist
• the most beautiful X-ray photographs of any
  substance ever taken
• (1952) crucial contributions to the solution of
  the structure of DNA

41

KEY PLAYERS Rosalind Franklin (1920-1958)
Franklin, trained as a chemist, was expert in
deducing the structure of molecules by firing
X-rays through them. Her images of DNA
disclosed without her knowledge - put Watson and
Crick on the track towards the right structure.
She went on to do pioneering work on the
structures of viruses.

42
The Evidence
Search for genetic material James Watson and
Francis Crick used this photo with other evidence
to describe the structure of DNA.
X-ray diffraction photo of DNA Image produced by
Rosalind Franklin
43
In July 1952, Erwin Chargaff visited Watson
and Crick and told of his 1947 findings that the
ratios of A/T and G/C were statistically equal
for a wide variety of DNAs. Crick became
convinced that base pairing was the key to the
structure. Prompted by receiving a flawed
manuscript on DNA structure from Pauling, Watson
again visited Kings and Wilkins showed him a DNA
x-ray pattern taken by Franklin showing clear
helical characteristics.
44
OOPS!!!
Watson brought back a less-than-accurate
account to Cambridge, but Crick produced a
three-strand model structure only a week later.
Invited to view this,Franklin pointed out that
it was inconsistent with her results it had the
phosphate groups on the inside whereas her
results showed they were on the outside,and the
water content was too low.
45
Watson Crick

What they deduced from Franklins X-ray data
Double helix Uniform width of 2 nm Bases
stacked 0.34 nm apart Chargoffs rules
Adenine pairs with thymine Cytosine pairs with
guanine
46
Watson Crick

What they came up with on their own Bases face
inward, phosphates and sugars outward
Hydrogen bonding Hinted at semi-conservative
model for replication
47
History
Watson began pursuing the idea of hydrogen
bonding by using cardboard cutouts of the four
bases. He found that (AT) and (GC) could be
bonded together to form pairs with very similar
shapes. On this basis, a model was built
consistent with the Franklins symmetry and
Chargaffs results, and Watson Crick published
in April 1953 in Nature accompanied by ones from
the Wilkins and Franklin groups. Watson and
Cricks paper ends with the oft-quoted line It
has not escaped our notice that the specific
pairing we have postulated immediately suggests a
possible copying mechanism for the genetic
material.
48
Watson and Crick with their
DNA model

49
The Nobel Prize

Crick, Watson and Wilkins won the Nobel Prize for
medicine in 1962. Maurice Wilkins was at King's
College, London and was an expert in X-ray
photography. His colleague, Rosalind Franklin,
did brilliant work developing the technique to
photograph a single strand of DNA. She received
little recognition for this at the time and died
tragically of cancer in 1958, so could not be
recognized in the Nobel Award.