How does the DNA lead to
specific traits???

Archibald Garrod (1909)
hypothesized: “proteins are the
link between genotype &
phenotype”
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.”
Example

Alkaptonuria
 where urine turns black after
exposure to air
enzyme
enzyme

enzyme
enzyme
•

G. Beadle & Edward
Tatum

Nobel Prize in Physiology or Medicine 1958
"for their discovery that genes act by regulating definite
chemical events"
One Gene, One Enzyme Hypothesis
-Beadle & Tatum

 each gene dictates the
production of one enzyme
 each mutant lacks the ability
to produce an enzyme
*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)
 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
Griffith’s transformation experiments

Oswald Avery

Frederick Griffith

Colin MacLeod
Established that DNA carries necessary
information for bacterial transformation
 Avery–MacLeod–McCarty

experiment
Hershey-Chase
experiments
Established that viral
DNA enters
bacterial cells
and is required for
synthesis of
new viral particles

Alfred Hershey

Martha Chase
 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
Nucleotide
subunits of DNA
x-ray

diffraction studies

Carried out by Rosalind Franklin
on crystals of purified DNA

Born: July 25, 1920
Died: April 16, 1958
X-ray diffraction image of DNA


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.


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.
 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
3-D model of
DNA double helix

James D. Watson
Francis Crick
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.
Base compositions in
DNA from selected
organisms
 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
Base pairing
and
hydrogen
bonding


DNA replication modes


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
 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
› Bidirectional, starting at origin of

replication
› Strands replicate at replication fork
› Two DNA polymerase molecules
catalyze replication
 Leading strand
 Lagging strand
Enzymes involved in
DNA replication
Simplified view of DNA replication
Overview of DNA replication
Leading
and
lagging
DNA
strands
Bidirectional DNA replication in bacteria and
eukaryotes
 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
Replication
at
chromosome
ends

DNA the carrier of genetic information

  • 2.
    How does theDNA lead to specific traits??? Archibald Garrod (1909) hypothesized: “proteins are the link between genotype & phenotype”
  • 3.
    1909 - ArchibaldGarrod  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.”
  • 4.
    Example Alkaptonuria  where urineturns black after exposure to air
  • 5.
  • 6.
    • G. Beadle &Edward Tatum Nobel Prize in Physiology or Medicine 1958 "for their discovery that genes act by regulating definite chemical events"
  • 10.
    One Gene, OneEnzyme Hypothesis -Beadle & Tatum  each gene dictates the production of one enzyme  each mutant lacks the ability to produce an enzyme
  • 11.
    *Some proteins arenot 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 DNAas 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
  • 13.
    Griffith’s transformation experiments OswaldAvery Frederick Griffith Colin MacLeod
  • 14.
    Established that DNAcarries necessary information for bacterial transformation
  • 15.
  • 16.
    Hershey-Chase experiments Established that viral DNAenters bacterial cells and is required for synthesis of new viral particles Alfred Hershey Martha Chase
  • 17.
     Structure ofDNA › 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
  • 18.
  • 20.
    x-ray diffraction studies Carried outby Rosalind Franklin on crystals of purified DNA Born: July 25, 1920 Died: April 16, 1958
  • 21.
  • 22.
     three major typesof regular, repeating patterns in the molecule with the dimensions 0.34 nanometer, 3.4 nanometers, and 2.0 nanometers were evident.
  • 23.
     Watson and Crickbegan 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 DNAmolecule › 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
  • 25.
    3-D model of DNAdouble helix James D. Watson Francis Crick
  • 26.
    Erwin Chargaff the basecomposition 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.
  • 27.
    Base compositions in DNAfrom selected organisms
  • 28.
     Base-pairing rules forDNA › 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
  • 29.
  • 30.
  • 31.
     DNA REPLICATION isSEMICONSERVATIVE  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
  • 33.
     DNA Replication › Twostrands 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, startingat origin of replication › Strands replicate at replication fork › Two DNA polymerase molecules catalyze replication  Leading strand  Lagging strand
  • 35.
  • 36.
    Simplified view ofDNA replication
  • 37.
    Overview of DNAreplication
  • 38.
  • 39.
    Bidirectional DNA replicationin bacteria and eukaryotes
  • 40.
     Replication › Telomeres atchromosome 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
  • 41.