2. How does the DNA lead to
specific traits???
Archibald Garrod (1909)
hypothesized: “proteins are the
link between genotype &
phenotype”
3. 1909 - Archibald Garrod
Suggested genes control
enzymes, & enzymes catalyze
chemical processes in cells.
Inherited Diseases are “inborn errors
of metabolism” where a person
can’t make an enzyme.”
6. •
G. Beadle & Edward
Tatum
Nobel Prize in Physiology or Medicine 1958
"for their discovery that genes act by regulating definite
chemical events"
7.
8.
9.
10. One Gene, One Enzyme Hypothesis
-Beadle & Tatum
each gene dictates the
production of one enzyme
each mutant lacks the ability
to produce an enzyme
11. *Some proteins are not enzymes
(ex. insulin)
*Some proteins are made of more than
one polypeptide chain (hemoglobin)
*Each chain specified by its own gene
One Gene, One Polypeptide
Hypothesis
-Beadle & Tatum (revisited)
12. Evidence
of DNA as
hereditary material
› Proteins rather than nucleic acids
thought to be genetic material in
the 1930s and 1940s
› Several lines of evidence supported
DNA as genetic material
DNA is transforming principle in
bacteria
› Watson and Crick modeled DNA
structure
17. Structure of DNA
› Regular polymer of nucleotides
Nitrogenous base of purine or
pyrimidine
Base covalently links to deoxyribose
Deoxyribose covalently bonds to a
phosphate group
› Backbone
Alternating sugar and phosphate
groups joined by covalent
phosphodiester linkages
22.
three major types of regular, repeating
patterns in the molecule with the
dimensions 0.34 nanometer, 3.4
nanometers, and 2.0 nanometers were
evident.
23.
Watson and Crick began to pursue the
problem of DNA structure
each pair of bases is exactly 0.34 nanometer
from the adjacent pairs above and below
Because exactly ten base pairs are present
in each full turn of the helix, each turn is 3.4
nanometers high
DNA molecule is 2.0 nm wide.
24. Structure
of DNA molecule
› Two polynucleotide chains associated
as double helix
› Two chains are antiparallel (running in
opposite directions)
› The sugar-phosphate backbones of
the two chains form the outside of the
helix
› The bases belonging to the two
chains associate as pairs in the center
26. Erwin Chargaff
the base composition of DNA from a
number of organisms and tissues had
been determined
Regardless of the source of the DNA
“ratios of purines to pyrimidines and
also of adenine to thymine and
ofguanine to cytosine were not far
from 1.
28. Base-pairing
rules for DNA
› Hydrogen bonding between base
pairs holds together the two chains
of helix
› Adenine (A) forms two hydrogen
bonds with thymine (T)
› Guanine (G) forms three hydrogen
bonds with cytosine (C)
› Chargaff’s rules
A=T
G=C
31.
DNA REPLICATION is SEMICONSERVATIVE
One way to accomplish this is to use a heavy-nitrogen
isotope,nitrogen-15 (ordinary nitrogen is nitrogen-14)
Matthew Meselson and Franklin Stahl grew cells of the
bacterium Escherichia coli on a medium that contained
nitrogen-15 in the form of ammonium chloride (NH4Cl)
Matthew Meselson
Franklin Stahl
32.
33. DNA
Replication
› Two strands of double helix unwind
› Each strand serves as template for
new strand
› DNA polymerase adds new
nucleotide subunits
› Additional enzymes and other
proteins required to unwind and
stabilize DNA helix
34. › Bidirectional, starting at origin of
replication
› Strands replicate at replication fork
› Two DNA polymerase molecules
catalyze replication
Leading strand
Lagging strand
40. Replication
› Telomeres
at chromosome ends
Short, non-coding repetitive DNA
sequences
Shorten slightly with each cell cycles
Can be extended by telomerase
Absence of telomerase activity may be
cause of cell aging
› Most cancer cells have telomerase to
maintain telomere length and resist
apoptosis
