Chapter 16
The Molecular
Basis of
Inheritance
Lecture Presentations by
Nicole Tunbridge and
© 2021 Pearson Education, Inc. Kathleen Fitzpatrick
Figure 16.1a
The elegant double-helical structure of deoxyribonucleic acid
(DNA) shook the scientific world when it was proposed in
April 1953 by James Watson and Francis Crick.
The DNA you inherited from your parents included all your
genes—your genetic information
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Figure 16.1b
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CONCEPT 16.1: DNA is the genetic material
• Early in the 20th century, the identification of the
molecules of inheritance posed a major challenge
to biologists
The Search for the Genetic Material: Scientific
Inquiry
• When T. H. Morgan’s group showed that genes are
located on chromosomes, the two components of
chromosomes—DNA and protein—became
candidates for the genetic material
• The role of DNA in heredity was first discovered
by studying bacteria and the viruses that
infect them
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Evidence That DNA Can Transform Bacteria
• The discovery of the genetic role of DNA began
with research by Frederick Griffith in 1928
• Griffith worked with two strains of a bacterium, one
pathogenic and one harmless
• When he mixed heat-killed remains of the
pathogenic strain with living cells of the harmless
strain, some living cells became pathogenic
• He called this phenomenon transformation, now
defined as a change in genotype and phenotype
due to assimilation of foreign DNA
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Figure 16.2
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• Later work by Oswald Avery, Maclyn McCarty, and
Colin MacLeod identified the transforming
substance as DNA
• Many biologists remained skeptical, mainly
because little was known about DNA
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Evidence That Viral DNA Can Program Cells
• More evidence for DNA as the genetic material
came from studies of viruses that infect bacteria
• Such viruses are called bacteriophages (or
phages)
• A virus is DNA (sometimes RNA) enclosed by a
protective coat, often simply protein
• Phages have been widely used as tools by
researchers in molecular genetics
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Figure 16.3
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• In 1952, Alfred Hershey and Martha Chase showed
that DNA is the genetic material of a phage known
as T2
• They designed an experiment showing that only
one of the two components of T2 (DNA or protein)
enters an E. coli cell during infection
• They concluded that the injected DNA of the phage
provides the genetic information
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Figure 16.4
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Additional Evidence That DNA Is the Genetic
Material
• DNA is a polymer of nucleotides, each consisting of
a nitrogenous base, a sugar, and a phosphate
group
• The nitrogenous bases can be adenine (A),
thymine (T), guanine (G), or cytosine (C)
• In 1950, Erwin Chargaff reported that DNA
composition varies from one species to the next
• This evidence of molecular diversity among
organisms made DNA a more credible candidate
for the genetic material
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• Two findings became known as Chargaff’s rules
– The base composition of DNA varies between
species
– In any species the number of A and T bases is equal
and the number of G and C bases is equal
• The basis for these rules was not understood until
the discovery of the double helix
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Figure 16.5
The structure of a DNA strand
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Building a Structural Model of DNA
• After DNA was accepted as the genetic material,
the challenge was to determine how its structure
accounts for its role in inheritance
• Maurice Wilkins and Rosalind Franklin used a
technique called X-ray crystallography to study
molecular structure
• Franklin produced a picture of the DNA molecule
using this technique
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Figure 16.6
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• Franklin’s X-ray crystallographic images of DNA
allowed James Watson to deduce that DNA was
helical
• The X-ray images also enabled Watson to deduce
the width of the helix and the spacing of the
nitrogenous bases
• The pattern in the photo suggested that the DNA
molecule was made up of two strands, forming a
double helix
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• Watson and Crick built models of a double helix to
conform to the X-rays and chemistry of DNA
• Franklin had concluded that there were two outer
sugar-phosphate backbones, with the nitrogenous
bases paired in the molecule’s interior
• Watson built a model in which the backbones were
antiparallel (their subunits run in opposite
directions)
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• At first, Watson and Crick thought the bases paired
like with like (A with A, and so on), but such pairings
did not result in a uniform width
• Instead, pairing a purine (A or G) with a pyrimidine
(C or T) resulted in a uniform width consistent with
the X-ray data
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• Watson and Crick reasoned that the pairing was
more specific, dictated by the base structures
• They determined that adenine (A) paired only with
thymine (T), and guanine (G) paired only with
cytosine (C)
• The Watson-Crick model explains Chargaff’s rules:
in any organism the amount of A = T, and the
amount of G = C
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Figure 16.9
Base pairing in DNA
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CONCEPT 16.2: Many proteins work together in
DNA replication and repair
• Resemblance of offspring to parents relies on
accurate replication of DNA prior to meiosis and its
transmission to the next generation
• Replication prior to mitosis ensures the faithful
transmission of genetic information from a parent
cell to the two daughter cells
• Watson and Crick noted that the specific base
pairing suggested a possible copying mechanism
for genetic material
• The copying of DNA is called DNA replication
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The Basic Principle: Base Pairing to a Template
Strand
• Since the two strands of DNA are complementary,
each strand acts as a template for building a new
strand in replication
• This yields two exact replicas of the “parental”
molecule
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Figure 16.10
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• Watson and Crick’s semiconservative model of
replication predicts that when a double helix
replicates, each daughter molecule will have one
old strand (derived or “conserved” from the parent
molecule) and one newly made strand
• Competing models were the conservative model
(the two parent strands rejoin) and the dispersive
model (each strand is a mix of old and new)
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Figure 16.11
Experiments by Matthew
Meselson and Franklin Stahl
supported the
semiconservative model
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DNA Replication: A Closer Look
• The copying of DNA is remarkable in its speed and
accuracy
• More than a dozen enzymes and other proteins
participate in DNA replication
• Replication in bacteria is best understood, but
evidence suggests that the replication process in
eukaryotes and prokaryotes is fundamentally
similar
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Getting Started
• Replication begins at particular sites called origins
of replication, where the two DNA strands are
separated, opening up a replication “bubble”
• A eukaryotic chromosome may have hundreds or
even thousands of origins of replication
• Replication proceeds in both directions from each
origin, until the entire molecule is copied
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Figure 16.13
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• At the end of each replication bubble is a
replication fork, a Y-shaped region where parental
DNA strands are being unwound
• Helicases are enzymes that untwist the double
helix at the replication forks
• Single-strand binding proteins bind to and
stabilize single-stranded DNA
• Topoisomerase relieves the strain of twisting of
the double helix by breaking, swiveling, and
rejoining DNA strands
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Figure 16.14
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Synthesizing a New DN A Strand
• D N A polymerases require a primer to which they
can add nucleotides
• The initial nucleotide chain is a short R N A primer
• This is synthesized by the enzyme primase
• The completed primer is five to ten nucleotides long
• The new D N A strand will start from the 3′ end of
the R N A primer
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• Enzymes called DNA polymerases catalyze the
synthesis of new DNA at a replication fork
• Most DNA polymerases require a primer and a DNA
template strand
• The rate of elongation is about 500 nucleotides per
second in bacteria and 50 per second in human
cells
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• Each nucleotide that is added to a growing DNA
strand is a nucleoside triphosphate
• dATP supplies adenine to DNA and is similar to the
ATP of energy metabolism
• The difference is in their sugars: dATP has
deoxyribose while ATP has ribose
• As each monomer joins the DNA strand, via a
dehydration reaction, it loses two phosphate groups
as a molecule of pyrophosphate
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Figure 16.15
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Antiparallel Elongation
• The antiparallel structure of the double helix affects
replication
• DNA polymerases add nucleotides only to the free
3′ end of a growing strand; therefore, a new DNA
strand can elongate only in the 5′ → 3′ direction
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• Along one template strand of DNA, the DNA
polymerase synthesizes a leading strand
continuously, moving toward the replication fork
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• To elongate the other new strand, called the
lagging strand, DNA polymerase must work in the
direction away from the replication fork
• The lagging strand is synthesized as a series of
segments called Okazaki fragments, which are
joined together by DNA ligase
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Figure 16.17
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Animation: DNA Replication: An Overview
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Figure 16.18
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Table 16.1
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The DNA Replication Complex
• The proteins that participate in DNA replication form
a large complex, a “DNA replication machine”
• The DNA replication machine may be stationary
during the replication process
• Recent studies support a model in which DNA
polymerase molecules “reel in” parental DNA and
extrude newly made daughter DNA molecules
• The exact mechanism is not yet resolved
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Figure 16.19
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Proofreading and Repairing DNA
• DNA polymerases proofread newly made DNA,
replacing any incorrect nucleotides
• In mismatch repair of DNA, repair enzymes
replace incorrectly paired nucleotides that have
evaded the proofreading process
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Nucleotide excision repair of DNA damage Nucleotide
excision repair of DNA damage
• DNA can be damaged by
exposure to harmful
chemical or physical agents
such as cigarette smoke
and X-rays; it can also
undergo spontaneous
changes
• In nucleotide excision
repair, a nuclease cuts out
and replaces damaged
stretches of DNA
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Evolutionary Significance of Altered DNA
Nucleotides
• The error rate after proofreading and repair is low
but not zero
• Sequence changes may become permanent and
can be passed on to the next generation
• These changes (mutations) are the source of the
genetic variation upon which natural selection
operates and are ultimately responsible for the
appearance of new species
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Replicating the Ends of DNA Molecules
• For linear DNA, the usual replication machinery
cannot complete the 5′ ends of daughter DNA
strands
• There is no 3′ end of a preexisting polynucleotide
for DNA polymerase to add on to
• Thus, repeated rounds of replication produce
shorter DNA molecules with uneven ends
• This is not a problem for prokaryotes, most of which
have circular chromosomes
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Figure 16.21
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• Eukaryotic chromosomal DNA molecules have
special nucleotide sequences at their ends called
telomeres
• Telomeres do not prevent the shortening of DNA
molecules, but they do postpone the erosion of
genes near the ends of DNA molecules
• It has been proposed that the shortening of
telomeres is connected to aging
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• If chromosomes of germ cells became shorter in
every cell cycle, essential genes would eventually
be missing from the gametes they produce
• An enzyme called telomerase catalyzes the
lengthening of telomeres in germ cells
• The shortening of telomeres might protect cells
from cancerous growth by limiting the number of
cell divisions
• There is evidence of telomerase activity in cancer
cells, which may allow cancer cells to persist
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CONCEPT 16.3: A chromosome consists of a
DNA molecule packed together with proteins
• The bacterial chromosome is a double-stranded,
circular DNA molecule associated with a small
amount of protein
• Eukaryotic chromosomes have linear DNA
molecules associated with a large amount
of protein
• In a bacterium, the DNA is “supercoiled” and found
in a region of the cell called the nucleoid
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• In the eukaryotic cell, DNA is precisely combined
with proteins in a complex called chromatin
• Chromosomes fit into the nucleus through an
elaborate, multilevel system of packing
• Proteins called histones are responsible for the
main level of DNA packing in interphase chromatin
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• In a 10-nm chromatin fiber, the unfolded chromatin
resembles beads on a string, with each “bead”
being a nucleosome
• A nucleosome is composed of DNA wound twice
around a core of eight histones, two each of the
four main histone types
• The amino end of each histone (the histone tail)
extends outward from the nucleosome and is
involved in regulation of gene expression
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Figure 16.23
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• Most chromatin is loosely packed in the nucleus
during interphase and condenses prior to mitosis
• Loosely packed chromatin is called euchromatin
• During interphase a few regions of chromatin
(centromeres and telomeres) are highly condensed
into heterochromatin
• Dense packing of the heterochromatin makes it
difficult for the cell to express genetic information
coded in these regions
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• Interphase chromosomes occupy specific restricted
regions in the nucleus, and the fibers of different
chromosomes do not become entangled
• Chromatin undergoes changes in packing during
the cell cycle
• As the cell prepares for mitosis, the chromatin is
organized into loops and coils, eventually
condensing into short, thick metaphase
chromosomes
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CONCEPT 16.3: A chromosome consists of a
DNA molecule packed together with proteins
• Histones can undergo chemical modifications that
result in changes in chromatin condensation
• These changes can also have multiple effects on
gene expression
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Figure 16.UN03
Summary of key concepts: many proteins work together
in DNA replication and repair
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