Landmark experiments showed that DNA is the
genetic material
Until the 1940s, the case for proteins serving as the genetic
material was stronger than the case for DNA.
– Proteins are made from 20 different amino acids.
– DNA was known to be made from just 4 kinds of
nucleotides.
▪ Studies of bacteria and viruses
– ushered in the field of molecular biology, the study of
heredity at the molecular level
– revealed the role of DNA in heredity.
In 1928, Frederick Griffith discovered that a “transforming factor”
could be transferred (by transformation) between bacterial cells
- the disease-causing characteristic was inherited by transformed cells
In 1952, Alfred Hershey and Martha Chase used bacteriophages to
show that DNA is the genetic material of T2, a virus that infects the
bacterium Escherichia coli (E. coli).
Phages were labeled with radioactive sulfur to detect proteins
or radioactive phosphorus to detect DNA
– Bacteria were infected with either type of labeled phage to
determine which substance was injected into cells and which
remained outside the infected cell
Phages were labeled with radioactive sulfur to detect proteins
or radioactive phosphorus to detect DNA
– Bacteria were infected with either type of labeled phage to
determine which substance was injected into cells and which
remained outside the infected cell
DNA injected by the phage carries the information that make the
bacteria make more viral phage particles
The discovery that DNA is a double
stranded helix
In 1952, after the Hershey-Chase
experiment demonstrated that
the genetic material was most
likely DNA, a race was on to
– describe the structure of DNA
and
– explain how the structure
and properties of DNA can
account for its role in
heredity
Deoxyribonucleic acid (DNA)
DNA is a polymer of nucleotides,
each consisting of a nitrogenous
base, a sugar, and a phosphate
group
DNA and RNA are polymers of nucleotides
The nitrogenous bases can be adenine (A), thymine (T), guanine (G),
or cytosine (C)
* In 1950, Erwin Chargaff measured the mass of each base in different
species, reported that:
1. DNA composition varies from one species to the next
2. The base composition of DNA varies between species
3. In any species the number of A and T bases is equal and the
number of G and C bases is equal
Rosalind Franklin, a graduate student
with Maurice Watkins, produced X-
ray image of DNA molecule
James Watson saw image and
together with Francis Crick
deduced the shape to be a
helix
The sugar-phosphate backbone is on the outside
* The nitrogenous bases are perpendicular to the backbone in the
interior
* Specific pairs of bases give the helix a uniform shape
Adenine pairs with Thymine
* Guanine pairs with CytosineDNA comprises
two anti-parallel
strands
End with the
phosphate group
is termed the 5’
end
End with the
hydroxyl group is
termed the 3’
end
DNA replication depends on specific base pairing
In their
description of
the structure of
DNA, Watson
and Crick noted
that the
structure of
DNA suggests a
possible
copying
mechanismDNA replication follows a semiconservative
model
DNA replication proceeds in two directions at many
sites simultaneously
DNA replication begins
at the origins of
replication where
– DNA unwinds at the
origin to produce a
“bubble,”
– replication proceeds
in both directions
from the origin, and
– replication ends
when products from
the bubbles merge
with each other.
DNA replication proceeds in the 5’ to 3’ direction
DNA replication occurs in
the 5’ to 3′ direction
– DNA polymerase
catalyzes synthesis of
new DNA by adding
nucleotides to the 3’
end of a pre-existing
chain
– Replication is
continuous on the 3′ to
5′ template.
– Replication is
discontinuous on the 5′
to 3′ template, forming
short segmentsDNA polymerase
adds nucleotides to a
growing chain and
proofreads and corrects
improper base pairings.
DNA ligase joins small
‘Okazaki fragments’ into
a continuous chain.
How do cells package this DNA into chromosomes?
Stretched out the DNA in your cells would measure about 4cm long
* Chromosomal DNA is wound around proteins called histones to form
chromatin
* Groups of 8 histones make nucleosomesNucleosomes coil into 30nm fibers which further loop in
looped 300nm fibers which further fold into chromosomes
Genomics is the scientific study of whole
genomes
Genomics is the study of an organism’s complete set of
genes and their interactions.
* The goals of the Human Genome Project (HGP) included
* determining the nucleotide sequence of all DNA in the
human genome and
* identifying the location and sequence of every human
gene
Draft Genome: Public approach vs Private
Book-by-book & page-
by-page sequencing
strategy
Book-by-book & page-
by-page sequencing
strategy
* Slow
* Labor-intensive &
very expensive
* Yields high-quality
output
Private approach:
Shotgun sequencing
strategy
* Fast
* Cheap
* Computationally
challenging
* Lower quality output
Human Genome Project
The Human Genome Project revealed that most of the
human genome does not consist of genes
Genomes contain different numbers of genesPersonalized genotyping: Costs $10-20,000 on insurance…..or $100
cash
