Chapter 12-13 –
DNA and How
Genes Work
DNA is the genetic material
• 1920’s – Griffith’s experiments on
transformation
• 1940’s - Avery, MacLeod and McCarty
demonstrated that transforming agent
was DNA
• 1952 – Hershey and Chase – definitive
evidence that DNA is hereditary material
• 1953 – Watson and Crick AND Franklin
Griffith experiment
Streptococcus pneumoniae
S strain - pathogenic
R strain - non-pathogenic
Frederick Griffith
(1879 – 1941)
Griffith experiment
Griffith experiment
Griffith experiment
Griffith experiment
Griffith experiment conclusion
• Hereditary information can pass between
cells = transformation
Avery, MacLeod and McCarty
• What is transforming agent? DNA or
protein?
Avery, MacLeod and McCarty
Avery, MacLeod and McCarty conclusion
• DNA carries the heritable information
1944
Hershey and Chase
Martha Cowles Chase
Alfred Day Hershey
Hershey and Chase
Bacteriophage: viruses that infect bacterial cells
Hershey and Chase
Hershey and Chase conclusion
• Genetic material in virus was
DNA
• DNA is agent of heredity
INDEPENDENT FUNCTIONS OF VIRAL PROTEIN AND NUCLEIC
ACID IN GROWTH OF BACTERIOPHAGE*
B~ A. D. HERSHEY AND MARTHA CHASE
(From the Department of Genetics, Carnegie Institution of Washington, Cold Spring
Harbor, Long Island)
(Received for publication, April 9, 1952)
The work of Doermaml (1948), Doermann and Dissosway (1949), and Anderson and Doermann (1952) has shown that
bacteriophages T2, T3, and T4 multiply in the bacterial cell in a non-infective form. The same is true of the phage carried by certain
lysogenic bacteria (Lwoff and Gutmann, 1950). Little else is known about the vegetative phase of these viruses. The experiments
reported in this paper show that one of the first steps in the growth of T2 is the release from its protein coat of the nucleic acid of the
virus particle, after which the bulk of the sulfur-containing protein has no further function.
DNA – just
what is it?
Nucleic Acids
Monomers =
nucleotides
Polymer =
DNA, RNA
DNA
Nucleotide
(monomer)
4 bases
Bases
Purines: A and G
Pyrimidines: T and C (and U in RNA)
Chargaff's rules
The proportion of A always equals T and
G always equals C.
A=T and G=C
Also
A+G = C+T
Rosalind Franklin
(1920-1958)
X-ray crystalography
Structure of DNA
Watson
and Crick
1953
Watson and Crick
(1953)
DNA
Structure
Replication
Expression
DNA Structure
*Double helix
*Complementarity
*Antiparallel
Double helix
Antiparallel
Complementarity
Base pairing in DNA
Purines always pair
with pyrimidines
Complementarity
A always with T
G always with C
DNA Replication
DNA
“double
helix”
DNA
“double
helix”
A-T
G-C
How does
replication
occur?
Conservative Model
Semi-conservative Model
Dispersive Model
DNA Replication
DNA Replication
Semiconservative replication
Meselson-Stahl experiment
Meselson-Stahl experiment
DNA replication occurs in semiconservative manner
THE REPLICATION OF DNA IN ESCHERICHIA COLI*
BY MATTHEW MESELSON AND FRANKLIN W. STAHL
GATES AND CRELLIN LABORATORIES OF CHEMISTRY, t AND NORMAN W. CHURCH LABORATORY OF
CHEMICAL BIOLOGY, CALIFORNIA INSTITUTE OF TECHNOLOGY, PASADENA, CALIFORNIA
Communicated by Max Delbrick, May 14, 1958
Introduction.-Studies of bacterial transformation and bacteriaphage infection'-‘ strongly indicate that deoxyribonucleic
acid (DNA) can carry and transmit hereditary information and can direct its own replication. Hypotheses for the
mechanism of DNA replication differ in the predictions they make concerning the distribution among progeny
molecules of atoms derived from parental molecules.6 Radioisotopic labels have been employed in experiments bearing
on the distribution of parental atoms among progeny molecules in several organisms.6-9 We anticipated that a label
which imparts to the DNA molecule an increased density might permit an analysis of this distribution by sedimentation
techniques. To this end, a method was developed for the detection of small density differences
1958
DNA
Replication
DNA Replication
DNA Replication
DNA
Replication
DNA
Replication
DNA
Replication
DNA
Expression
DNA
Information stored in
order of the bases
+/- 1200 copies
Central Dogma of Cell Biology
DNA (gene)
Protein
One-Gene/One-Polypeptide Hypothesis
Each gene codes for a
specific and unique protein
1958 – Nobel Prize
GENETICS: TA TUM AND BEADLE
GENETIC CONTROL OF BIOCHEMICAL REACTIONS IN NEUROSPORA:
AN "AMINOBENZOICLESS" MUTANT*
By E. L. TATUM AND G. W. BEADLE
DEPARTMENT OF BIOLOGY, STANFORD UNIVERSITY
Communicated April 17, 1942
Para-aminobenzoic acid has recently been recognized as a factor required for the growth of a number of micro6rganisms' and as
a member of the vitamin B group.2 One of the number of x-ray induced mutants of Neurospora crassa, obtained as described
elsewhere,' is characterized by the loss of ability to synthesize p-aminobenzoic acid. This "aminobenzoicless“ mutant is
differentiated from normal by a single gene, is unable to grow on unsupplemented synthetic medium, but its growth is
indistinguishable from normal when p-aminobenzoic acid is supplied.
Central dogma of molecular biology
Extracting and using the information
Two Steps:
1.
2.
Extracting and using the information
The information
Extracting and using the information
An intermediate
Extracting and using the information
The product
Translation – constructing
a protein
DNA
mRNA
protein
Transcription
DNA copied
into mRNA
mRNA
single-stranded
U instead
of T
Translation – constructing
a protein
DNA
mRNA
protein
Instructions are coded in
the order of the bases
Instructions are an ordered list
of amino acids in protein
20 amino
acids
Protein is a polymer of
amino acids
Each ‘word’ in the DNA-RNA
vocabulary is 3 ‘letters’ long
One “word”
Each ‘word’ in the DNA-RNA
vocabulary is 3 ‘letters’ long
A ‘word’ is
called a codon
Triplet Codon:
group of 3 bases that
specifies an amino acid
The Genetic Code
-Redundant
-Not ambiguous
-Stop codons
-AUG - start
-Universal (nearly)
Marshal W. Nirenberg
Universal (nearly)
The Dictionary
Punch tape
tRNA
mRNA
Ribosome
tRNA brings
in the amino
acides
Translation
Translation
Translation
Translation
Translation
Translation
Universal (nearly)
Reading frames
Reading frames
the red dog ate the bug
her edd oga tet heb ug