Transcript The History of Molecular Genetics

The History of Molecular
Genetics
The early contributions:
setting the stage

Gregor Mendel: mid 1800’s
Gregor Mendel

By studying pea plants, determined:
– Characteristics are inherited in discrete
units (later called genes)
– Inherited units are independently
segregated and assorted
– Inherited units can be dominant or
recessive
The early contributions:
setting the stage

Thomas Hunt Morgan: early 1900’s
– Worked at Columbia University; later at
CalTech
– Studied fruit fly eye color, determining
that trait was sex-linked
– Won the Nobel Prize in 1933 for his work
on chromosomes and genetics
Thomas Hunt Morgan
The early contributions:
setting the stage



By this point, it was known that genetic
material was located on a
chromosome
This genetic material was in discrete
units called genes
It was NOT known whether the gene
was simply a protein, or whether it was
composed of DNA
Frederick Griffith




Late 1920’s
From Britain
Worked with bacteria called
Streptococcus pneumoniae
Defined the term,
“TRANSFORMATION”
Frederick Griffith: the
transforming principle
Transformation


Change in a genotype and phenotype
due to the incorporation of external
DNA by a cell
How did Griffith know that the dead
mouse was killed by transformed
bacteria?
Transformation

The dead mouse had living virulent
bacteria in its blood
Oswald Avery

American biologist and physician
– Born in Canada, but grew up in NYC



Worked in the 1930’s – 1950’s
Also worked with the transformation
principle
Colleagues—McCarty and MacLeod
Oswald Avery

Avery’s work involved separating DNA and
proteins, and then
attempting to see
which substance could
transform live,
nonpathogenic
bacteria into
pathogenic bacteria
Oswald Avery

Avery’s conclusion:
– DNA is the transforming substance

However……most scientists at the time still
believed that the transforming substance was
a protein
Hershey and Chase



Alfred Hershey; Martha Chase
Early 1950’s
Used phages
– Viruses used to infect bacteria
– Called “T2” phages

Their question: which part of the
virus—protein coat or DNA—in
responsible for transforming E. coli ?
Hershey and Chase
T2 PHAGE
Hershey and Chase
Experiment
Hershey and Chase

Conclusion:
– DNA IS RESPONSIBLE FOR
TRANSFORMATION OF BACTERIA,
NOT PROTEINS
– THEREFORE, DNA IS THE
HEREDITARY MATERIAL
Erwin Chargaff




Biochemist
Died in 2002
Worked at Columbia University since
1950’s
Studied proportion of purines and
pyrimidines in DNA
Erwin Chargaff

Findings: CHARGAFF’S RULES
– DNA composition varies between
different species
– In a given species, the four nitrogen
bases are present in a predictable ratio
Chargaff’s Rules

Human DNA:
–
–
–
–


A = 30.9%
T = 29.4%
G = 19.9%
C = 19.8%
A = T; G = C
Chargaff couldn’t explain this, but this
information later became crucial to Watson
and Crick
THE RACE IS ON!
Who discovers the double helix?
Linus Pauling


Worked at CalTech
Died in 1994
– Won Nobel prize in chemistry in 1954 for
work in chemical bonding; Nobel peace
prize in 1962 for his campaign against
above-ground nuclear testing
Linus Pauling
Linus Pauling

He also worked on the structure of
DNA, but came up with a TRIPLE
HELIX
– He thought DNA was 3 strands with the
phosphates on the inside
Franklin and Wilkins


Rosalind Franklin; Maurice Wilkins
Worked in London
Franklin and Wilkins


Used X-ray crystallography to look at
the shape of DNA
Their information gave Watson and
Crick the necessary information they
needed to come up with the double
helix structure
– Width of the helix
– Spacing of the nitrogenous bases
James Watson and
Francis Crick
James Watson and
Francis Crick


Used wire models to conform with the
measurements that Franklin and
Wilkins had come up with
Determined the structure to be a
double helix
James Watson and
Francis Crick


Won the Nobel prize in medicine in
1962 for their discovery
Maurice Wilkins was also included in
winning the Nobel prize
– Who was excluded???

Avery, Franklin, Chargaff, Pauling, and about
20+ other scientists who were instrumental in
discovering the shape of DNA
– Rosalind Franklin had died in 1958; Avery died in
1955
James Watson and
Francis Crick
James Watson and
Francis Crick


Crick died in 2004
Watson is still living, though recently
forced to resign his administrative job
at Cold Spring Harbor labs due to
racist statements