Prokaryotic eukaryoticgenome

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Genetics of Viruses and Bacteria
• Viruses called bacteriophages
– Can infect and set in motion a genetic takeover
of bacteria, such as Escherichia coli

• Recall that bacteria are prokaryotes
– With cells much smaller and more simply
organized than those of eukaryotes
• Viruses
– Are smaller and simpler still
Figure 18.2
0.25 m
Virus
Animal
cell
Bacterium
Animal cell nucleus

• A virus has a genome but can reproduce only
within a host cell
• Scientists were able to detect viruses indirectly
– Long before they were actually able to see
them
Figure 18.3
For example: Tobacco mosaic disease
stunts the growth of tobacco plants
and gives their leaves a mosaic
coloration

• In the late 1800s
– Researchers hypothesized that a particle
smaller than bacteria caused tobacco mosaic
disease
• In 1935, Wendell Stanley
– Confirmed this hypothesis when he crystallized
the infectious particle, now known as tobacco
mosaic virus (TMV)

Structure of Viruses
• Viruses
– Are very small infectious particles consisting of
nucleic acid enclosed in a protein coat and, in
some cases, a membranous envelope
• Viral genomes may consist of
– Double- or single-stranded DNA
– Double- or single-stranded RNA

Figure 18.4a, b
18  250 mm 70–90 nm (diameter)
20 nm 50 nm
(a) Tobacco mosaic virus (b) Adenoviruses
RNA
DNACapsomere
Glycoprotein
Capsomere
of capsid
Capsids and Envelopes
• A capsid
– Is the protein shell that encloses the viral genome
– Can have various structures

• Some viruses have envelopes
– Which are membranous coverings derived
from the membrane of the host cell
Figure 18.4c
80–200 nm (diameter)
50 nm
(c) Influenza viruses
RNA
Glycoprotein
Membranous
envelope
Capsid

• Bacteriophages, also called phages
– Have the most complex capsids found among
viruses
Figure 18.4d
80  225 nm
50 nm
(d) Bacteriophage T4
DNA
Head
Tail
fiber
Tail
sheath

General Features of Viral Reproductive Cycles
• Viruses are obligate intracellular parasites
– They can reproduce only within a host cell
• Each virus has a host range
– A limited number of host cells that it can infect

• Viruses use enzymes, ribosomes, and small
molecules of host cells
– To synthesize progeny viruses
VIRUS
Capsid
proteins
mRNA
Viral DNA
HOST CELL
Viral DNA
DNA
Capsid
Figure 18.5
Entry into cell and
uncoating of DNA
Replication
Transcription
Self-assembly of
new
virus particles and
their exit from cell

Reproductive Cycles of Phages
• Phages
– Are the best understood of all viruses
– Go through two alternative reproductive
mechanisms: the lytic cycle and the lysogenic
cycle

The Lytic Cycle
• The lytic cycle
– Is a phage reproductive cycle that culminates
in the death of the host
– Produces new phages and digests the host’s
cell wall, releasing the progeny viruses

• The lytic cycle of phage T4, a virulent phage
Phage assembly
Head Tails Tail fibersFigure 18.6
Attachment. The T4 phage uses
its tail fibers to bind to specific
receptor sites on the outer
surface of an E. coli cell.
1
Entry of phage DNA
and degradation of host DNA.
The sheath of the tail contracts,
injecting the phage DNA into
the cell and leaving an empty
capsid outside. The cell’s
DNA is hydrolyzed.
2
Synthesis of viral genomes
and proteins. The phage DNA
directs production of phage
proteins and copies of the phage
genome by host enzymes, using
components within the cell.
3Assembly. Three separate sets of proteins
self-assemble to form phage heads, tails,
and tail fibers. The phage genome is
packaged inside the capsid as the head forms.
4
Release. The phage directs production
of an enzyme that damages the bacterial
cell wall, allowing fluid to enter. The cell
swells and finally bursts, releasing 100
to 200 phage particles.
5

The Lysogenic Cycle
• The lysogenic cycle
– Replicates the phage genome without
destroying the host
• Temperate phages
– Are capable of using both the lytic and
lysogenic cycles of reproduction

• The lytic and lysogenic cycles of phage λ, a
temperate phage
Many cell divisions
produce a large
population of bacteria
infected with the
prophage.
The bacterium reproduces
normally, copying the prophage
and transmitting it to daughter cells.
Phage DNA integrates into
the bacterial chromosome,
becoming a prophage.
New phage DNA and
proteins are synthesized
and assembled into phages.
Occasionally, a prophage
exits the bacterial chromosome,
initiating a lytic cycle.
Certain factors
determine whether
The phage attaches to a
host cell and injects its DNA.
Phage DNA
circularizes
The cell lyses, releasing phages.
Lytic cycle
is induced
Lysogenic cycle
is entered
Lysogenic cycleLytic cycle
or Prophage
Bacterial
chromosome
Phage
Phage
DNA
Figure 18.7

Viral Envelopes
• Many animal viruses
– Have a membranous envelope
• The broadest variety of RNA
genomes
– Is found among the viruses that
infect animals
• Viral glycoproteins on the envelope
– Bind to specific receptor
molecules on the surface of a
host cell
Table 18.1

RNA
Capsid
Envelope (with
glycoproteins)
HOST CELL
Viral genome (RNA)
Template
Capsid
proteins
Glyco-
proteins
mRNA
Copy of
genome (RNA)
ER
Figure 18.8
• The reproductive cycle of an enveloped RNA virus
Glycoproteins on the viral envelope
bind to specific receptor molecules
(not shown) on the host cell,
promoting viral entry into the cell.
1
Capsid and viral genome
enter cell
2
The viral genome (red)
functions as a template for
synthesis of complementary
RNA strands (pink) by a viral
enzyme.
3
New copies of viral
genome RNA are made
using complementary RNA
strands as templates.
4
Complementary RNA
strands also function as mRNA,
which is translated into both
capsid proteins (in the cytosol)
and glycoproteins for the viral
envelope (in the ER).
5
Vesicles transport
envelope glycoproteins to
the plasma membrane.
6
A capsid assembles
around each viral
genome molecule.
7
New virus8

• Retroviruses, such as HIV, use the enzyme
reverse transcriptase
– To copy their RNA genome into DNA, which
can then be integrated into the host genome
as a provirus
Figure 18.9
Reverse
transcriptase
Viral envelope
Capsid
Glycoprotein
RNA
(two identical
strands)

• The reproductive cycle of HIV, a retrovirus
Figure 18.10
mRNA
RNA genome
for the next
viral generation
Viral RNA
RNA-DNA
hybrid
DNA
Chromosomal
DNA
NUCLEUS
Provirus
HOST CELL
Reverse
transcriptase
New HIV leaving a cell
HIV entering a cell
0.25 µm
HIV Membrane of
white blood cell
The virus fuses with the
cell’s plasma membrane.
The capsid proteins are
removed, releasing the
viral proteins and RNA.
1
Reverse transcriptase
catalyzes the synthesis of a
DNA strand complementary
to the viral RNA.
2
Reverse transcriptase
catalyzes the synthesis of
a second DNA strand
complementary to the first.
3
The double-stranded
DNA is incorporated
as a provirus into the
cell’s DNA.
4
Proviral genes are
transcribed into RNA
molecules, which serve as
genomes for the next viral
generation and as mRNAs
for translation into viral
proteins.
5
The viral proteins include
capsid proteins and reverse
transcriptase (made in the
cytosol) and envelope
glycoproteins (made in the ER).
6
Vesicles transport the
glycoproteins from the ER to
the cell’s plasma membrane.
7Capsids are
assembled around
viral genomes and
reverse transcriptase
molecules.
8
New viruses bud
off from the host cell.
9

Evolution of Viruses
• Viruses do not really fit our definition of living
organisms (no cellular structure)
• Viruses, viroids, and prions are formidable
pathogens in animals and plants
• Diseases caused by viral infections
– Affect humans, agricultural crops, and
livestock worldwide

Viral Diseases in Animals
• Viruses may damage or kill cells
– By causing the release of hydrolytic enzymes
from lysosomes
• Some viruses cause infected cells
– To produce toxins that lead to disease
symptoms

• Vaccines
– Are harmless derivatives of pathogenic
microbes that stimulate the immune system to
mount defenses against the actual pathogen
– Can prevent certain viral illnesses
• Emerging viruses
– Are those that appear suddenly or suddenly
come to the attention of medical scientists

• Severe acute respiratory syndrome (SARS)
– Recently appeared in China
(a) Young ballet students in Hong
Kong wear face masks to protect
themselves from the virus causing
SARS.
(b) The SARS-causing agent is a coronavirus
like this one (colorized TEM), so named for
the “corona” of glycoprotein spikes protruding
from the envelope.
Outbreaks of “new” viral diseases in humans
Are usually caused by existing viruses that
expand their host territory

Viral Diseases in Plants
• More than 2,000 types of viral diseases of
plants are known
• Common symptoms of viral infection include
– Spots on leaves and fruits, stunted growth, and
damaged flowers or roots
Figure 18.12

• Plant viruses spread disease in two major
modes
– Horizontal transmission, entering through
damaged cell walls
– Vertical transmission, inheriting the virus from
a parent

Viroids and Prions: The Simplest Infectious Agents
• Viroids
– Are circular RNA molecules that infect plants and disrupt their
growth
• Prions
– Are slow-acting, virtually indestructible infectious proteins that
cause brain diseases in mammals
– Propagate by converting normal proteins into the prion version
Figure 18.13
Prion
Normal
protein
Original
prion
New
prion
Many prions

• Rapid reproduction, mutation, and genetic
recombination contribute to the genetic
diversity of bacteria
• Bacteria allow researchers
– To investigate molecular genetics in the
simplest true organisms

The Bacterial Genome and Its Replication
• The bacterial chromosome
– Is usually a circular DNA molecule with few
associated proteins
• In addition to the chromosome
– Many bacteria have plasmids, smaller circular
DNA molecules that can replicate
independently of the bacterial chromosome

• Bacterial cells divide by binary fission
– Which is preceded by replication of the
bacterial chromosome
Replication
fork
Origin of
replication
Termination
of replication
Figure 18.14

Mutation and Genetic Recombination as Sources
of Genetic Variation
• Since bacteria can reproduce rapidly
– New mutations can quickly increase a
population’s genetic diversity

Mechanisms of Gene Transfer and Genetic
Recombination in Bacteria
• Three processes bring bacterial DNA from
different individuals together
– Transformation
– Transduction
– Conjugation

Transformation
• Transformation
– Is the alteration of a bacterial cell’s genotype
and phenotype by the uptake of naked, foreign
DNA from the surrounding environment

Transduction
• In the process known as transduction
– Phages carry bacterial genes from one host
cell to another
1
Figure 18.16
Donor
cell
Recipient
cell
A+
B+
A+
A+
B–
A–
B–
A+
Recombinant cell
Crossing
over
Phage infects bacterial cell that has alleles A+
and B+
Host DNA (brown) is fragmented, and phage DNA
and proteins are made. This is the donor cell.
A bacterial DNA fragment (in this case a fragment with
the A+
allele) may be packaged in a phage capsid.
Phage with the A+
allele from the donor cell infects
a recipient A–
B–
cell, and crossing over (recombination)
between donor DNA (brown) and recipient DNA
(green) occurs at two places (dotted lines).
The genotype of the resulting recombinant cell (A+
B–
)
differs from the genotypes of both the donor (A+
B+
) and
the recipient (A–
B–
).
2
3
4
5
Phage DNA
A+ B+

Conjugation and Plasmids
• Conjugation
– Is the direct transfer of genetic material between
bacterial cells that are temporarily joined
Figure 18.17 Sex pilus 1 m

The F Plasmid and Conjugation
• Cells containing the F plasmid, designated F+
cells
– Function as DNA donors during conjugation
– Transfer plasmid DNA to an F−
recipient cell
Figure 18.18a
A cell carrying an F plasmid
(an F+
cell) can form a
mating bridge with an F–
cell
and transfer its F plasmid.
A single strand of the
F plasmid breaks at a
specific point (tip of blue
arrowhead) and begins to
move into the recipient cell.
As transfer continues, the
donor plasmid rotates
(red arrow).
2 DNA replication occurs in
both donor and recipient
cells, using the single
parental strands of the
F plasmid as templates
to synthesize complementary
strands.
3 The plasmid in the
recipient cell
circularizes. Transfer
and replication result
in a compete F plasmid
in each cell. Thus, both
cells are now F+
.
4
F Plasmid Bacterial chromosome
Bacterial
chromosome
F+
cell
F+
cell
F+
cell
Mating
bridge
1
Conjugation and transfer of an
F plasmid from an F+
donor to
an F–
recipient
(a)
F–
cell

• Chromosomal genes can be transferred during
conjugation
– When the donor cell’s F factor is integrated into the
chromosome
• A cell with the F factor built into its chromosome
– Is called an Hfr cell
• The F factor of an Hfr cell
– Brings some chromosomal DNA along with it when it
is transferred to an F–
cell

• Conjugation and transfer of part of the
bacterial chromosome from an Hfr donor
to an F–
recipient, resulting in recombination
F+
cell Hfr cell
F factor
The circular F plasmid in an F+
cell
can be integrated into the circular
chromosome by a single crossover
event (dotted line).
1
The resulting cell is called an Hfr cell
(for High frequency of recombination).
2
Since an Hfr cell has all
the F-factor genes, it can
form a mating bridge with
an F–
cell and transfer DNA.
3 A single strand of the F factor
breaks and begins to move
through the bridge. DNA
replication occurs in both donor
and recipient cells, resulting in
double-stranded DNA
4 The location and orientation
of the F factor in the donor
chromosome determine
the sequence of gene transfer
during conjugation. In this
example, the transfer sequence
for four genes is A-B-C-D.
5 The mating bridge
usually breaks well
before the entire
chromosome and
the rest of the
F factor are transferred.
6
Two crossovers can result
in the exchange of similar
(homologous) genes between
the transferred chromosome fragment
(brown) and the recipient cell’s
chromosome (green).
7 The piece of DNA ending up outside the
bacterial chromosome will eventually be
degraded by the cell’s enzymes. The recipient
cell now contains a new combination of genes
but no F factor; it is a recombinant F–
cell.
8
Temporary
partial
diploid
Recombinant F–
bacterium
A+
B+
C+
D+
F–
cell A–
B–
C–
D–
A–
B–
C–
D– D–
A–
C–
B–
A+
B+C+D+
A+B+
D+
C+
A+
A+
B+
A–
B–
C–
D–
A–
B+
C–
D–
A+
B+
B–
A+
Hfr cell
D–
A–
C–
B–
A+
B+C+D+
A+
B+
Conjugation and transfer of part
of the bacterial chromosome from
an Hfr donor to an F–
recipient,
resulting in recombination
(b)
Figure 18.18b

R plasmids and Antibiotic Resistance
• R plasmids
– Confer resistance to various antibiotics
• Transposable elements
– Can move around within a cell’s genome
– Are often called “jumping genes”
– Contribute to genetic shuffling in bacteria

Figure 18.19a
(a) Insertion sequences, the simplest transposable elements in bacteria, contain a single gene that
encodes transposase, which catalyzes movement within the genome. The inverted repeats are
backward, upside-down versions of each other; only a portion is shown. The inverted repeat
sequence varies from one type of insertion sequence to another.
Insertion sequence
Transposase geneInverted
repeat
Inverted
repeat
3
5
3
5
A T C C G G T…
T A G G C C A …
A C C G G A T…
T G G C C T A …
Insertion Sequences
• An insertion sequence contains a single gene
for transposase
– An enzyme that catalyzes movement of the
insertion sequence from one site to another
within the genome

Transposons
• Bacterial transposons
– Also move about within the bacterial genome
– Have additional genes, such as those for
antibiotic resistance
Figure 18.19b
(b) Transposons contain one or more genes in addition to the transposase gene. In the transposon
shown here, a gene for resistance to an antibiotic is located between twin insertion sequences.
The gene for antibiotic resistance is carried along as part of the transposon when the transposon
is inserted at a new site in the genome.
Inverted repeats Transposase gene
Insertion
sequence
Insertion
sequence
Antibiotic
resistance gene
Transposon
5
3
5
3

• Individual bacteria respond to environmental
change by regulating their gene expression
• E. coli, a type of bacteria that lives in the
human colon
– Can tune its metabolism to the changing
environment and food sources

• This metabolic control occurs on two levels
– Adjusting the activity of metabolic enzymes
already present
– Regulating the genes encoding the metabolic
enzymes
Figure 18.20a, b
(a) Regulation of enzyme
activity
Enzyme 1
Enzyme 2
Enzyme 3
Enzyme 4
Enzyme 5
Regulation
of gene
expression
Feedback
inhibition
Tryptophan
Precursor
(b) Regulation of enzyme
production
Gene 2
Gene 1
Gene 3
Gene 4
Gene 5
–
–

Operons: The Basic Concept
• In bacteria, genes are often clustered into
operons, composed of
– An operator, an “on-off” switch
– A promoter
– Genes for metabolic enzymes

• An operon
– Is usually turned “on”
– Can be switched off by a protein called a
repressor

Video Clip – trp operon
• The trp operon: regulated synthesis of
repressible enzymes
Figure 18.21a
(a) Tryptophan absent, repressor inactive, operon on. RNA polymerase attaches to the DNA at the
promoter and transcribes the operon’s genes.
Genes of operon
Inactive
repressor
Protein
Operator
Polypeptides that make up
enzymes for tryptophan synthesis
Promoter
Regulatory
gene
RNA
polymerase
Start codon Stop codon
Promoter
trp operon
5
3
mRNA 5
trpDtrpE trpC trpB trpAtrpRDNA
mRNA
E D C B A

DNA
mRNA
Protein
Tryptophan
(corepressor)
Active
repressor
No RNA made
Tryptophan present, repressor active, operon off. As tryptophan
accumulates, it inhibits its own production by activating the repressor protein.
(b)
Figure 18.21b

Repressible and Inducible Operons: Two Types of
Negative Gene Regulation
• In a repressible operon
– Binding of a specific repressor protein to the
operator shuts off transcription
• In an inducible operon
– Binding of an inducer to an innately inactive
repressor inactivates the repressor and turns
on transcription

Video Clip – Lac Operon
• The lac operon: regulated synthesis of
inducible enzymes
Figure 18.22a
DNA
mRNA
Protein
Active
repressor
RNA
polymerase
No
RNA
made
lacZlacl
Regulatory
gene
Operator
Promoter
Lactose absent, repressor active, operon off. The lac repressor is innately active, and in
the absence of lactose it switches off the operon by binding to the operator.
(a)
5
3

mRNA 5'
DNA
mRNA
Protein
Allolactose
(inducer)
Inactive
repressor
lacl lacz lacY lacA
RNA
polymerase
Permease Transacetylase-Galactosidase
5
3
(b) Lactose present, repressor inactive, operon on. Allolactose, an isomer of lactose, derepresses
the operon by inactivating the repressor. In this way, the enzymes for lactose utilization are induced.
mRNA 5
lac operon
Figure 18.22b

• Inducible enzymes
– Usually function in catabolic pathways (break
down)
• Repressible enzymes
– Usually function in anabolic pathways (build
up)

• Regulation of both
the trp and lac
operons
– Involves the
negative control
of genes,
because the
operons are
switched off by
the active form of
the repressor
protein Figure 18.22a
DNA
mRNA
Protein
Active
repressor
RNA
polymerase
No
RNA
made
lacZlacl
Regulatory
gene Operator
Promoter
Lactose absent, repressor active, operon off.(a)
5
3
DNA
mRNA
Protein
Tryptophan
(corepressor)
Active
repressor
No RNA made
Tryptophan present, repressor active,
operon off
(b)
Figure 18.21b

Positive Gene Regulation
• Some operons are also subject to positive
control
– Via a stimulatory activator protein, such as
catabolite activator protein (CAP)

Promoter
Lactose present, glucose scarce (cAMP level high): abundant lac mRNA synthesized.
If glucose is scarce, the high level of cAMP activates CAP, and the lac operon produces
large amounts of mRNA for the lactose pathway.
(a)
CAP-binding site OperatorRNA
polymerase
can bind
and transcribe
Inactive
CAP
Active
CAP
cAMP
DNA
Inactive lac
repressor
lacl lacZ
Figure 18.23a
• In E. coli, when glucose, a preferred food
source, is scarce
– The lac operon is activated by the binding of a
regulatory protein, catabolite activator protein
(CAP)

Video Clip
• When glucose levels in an E. coli cell increase
– CAP detaches from the lac operon, turning it
off
Figure 18.23b
(b)Lactose present, glucose present (cAMP level low): little lac mRNA synthesized.
When glucose is present, cAMP is scarce, and CAP is unable to stimulate transcription.
Inactive lac
repressor
Inactive
CAP
DNA
RNA
polymerase
can’t bind
Operator
lacl lacZ
CAP-binding site
Promoter

Eukaryotic Genomes
• In eukaryotes, the DNA-protein complex, called
chromatin
– Is ordered into higher structural levels than the
DNA-protein complex in prokaryotes
Figure 19.1

• Chromatin structure is based on successive
levels of DNA packing
• Eukaryotic DNA
– Is precisely combined with a large amount of
protein
• Eukaryotic chromosomes
– Contain an enormous amount of DNA relative
to their condensed length

Nucleosomes, or “Beads on a String”
• Proteins called histones
– Are responsible for the first level of DNA
packing in chromatin
– Bind tightly to DNA
• The association of DNA and histones
– Seems to remain intact throughout the cell
cycle

• In electron micrographs
– Unfolded chromatin has the appearance of beads
on a string
• Each “bead” is a nucleosome
– The basic unit of DNA packing
Figure 19.2 a
2 nm
10 nm
DNA double helix
Histone
tails
His-
tones
Linker DNA
(“string”)
Nucleosome
(“bad”)
Histone H1
(a) Nucleosomes (10-nm fiber)

Nucleosome
30 nm
(b) 30-nm fiber
Higher Levels of DNA Packing
• The next level of packing
– Forms the 30-nm chromatin fiber
Figure 19.2 b

• The 30-nm fiber, in turn
– Forms looped domains, making up a 300-nm
fiber
Figure 19.2 c
Protein scaffold
300 nm
(c) Looped domains (300-nm fiber)
Loops
Scaffold

• In a mitotic chromosome
– The looped domains themselves coil and fold
forming the characteristic metaphase
chromosome
Figure 19.2 d
700 nm
1,400 nm
(d) Metaphase chromosome

• In interphase cells
– Most chromatin is in the highly extended form
called euchromatin

• Gene expression can be regulated at any
stage, but the key step is transcription
• All organisms
– Must regulate which genes are expressed at
any given time
• During development of a multicellular organism
– Its cells undergo a process of specialization in
form and function called cell differentiation

Differential Gene Expression
• Each cell of a multicellular
eukaryote
– Expresses only a fraction of its
genes
• In each type of differentiated
cell
– A unique subset of genes is
expressed
Figure 19.3
Signal
NUCLEUS
Chromatin
Chromatin modification:
DNA unpacking involving
histone acetylation and
DNA demethlation
Gene
DNA
Gene available
for transcription
RNA Exon
Transcription
Primary transcript
RNA processing
Transport to cytoplasm
Intron
Cap mRNA in nucleus
Tail
CYTOPLASM
mRNA in cytoplasm
Degradation
of mRNA
Translation
Polypetide
Cleavage
Chemical modification
Transport to cellular
destination
Active protein
Degradation of protein
Degraded protein

Histone Modification
• Chemical modification of histone tails
– Can affect the configuration of chromatin and
thus gene expression
Figure 19.4a (a) Histone tails protrude outward from a nucleosome
Chromatin changes
Transcription
RNA processing
mRNA
degradation
Translation
Protein processing
and degradation
DNA
double helix
Amino acids
available
for chemical
modification
Histone
tails

• Histone acetylation
– Seems to loosen chromatin structure and
thereby enhance transcription
Figure 19.4 b
(b) Acetylation of histone tails promotes loose chromatin structure that
permits transcription
Unacetylated histones Acetylated histones

Organization of a Typical Eukaryotic Gene
• Associated with most eukaryotic genes are
multiple control elements
– Segments of noncoding DNA that help regulate
transcription by binding certain proteins
Figure 19.5
Enhancer
(distal control elements)
Proximal
control elements
DNA
Upstream
Promoter
Exon Intron Exon Intron
Poly-A signal
sequence
Exon
Termination
region
Transcription
Downstream
Poly-A
signal
ExonIntronExonIntronExonPrimary RNA
transcript
(pre-mRNA)
5
Intron RNA
RNA processing:
Cap and tail added;
introns excised and
exons spliced together
Coding segment
P P PGmRNA
5 Cap 5 UTR
(untranslated
region)
Start
codon
Stop
codon
3 UTR
(untranslated
region)
Poly-A
tail
Chromatin changes
Transcription
RNA processing
mRNA
degradation
Translation
Protein processing
and degradation
Cleared 3 end
of primary
transport

Enhancers and Specific Transcription Factors
• Proximal control elements
– Are located close to the promoter
• Distal control elements, groups of which are
called enhancers
– May be far away from a gene or even in
an intron

Distal control
element
Activators
Enhancer
Promoter
Gene
TATA
box General
transcription
factors
DNA-bending
protein
Group of
Mediator proteins
RNA
Polymerase II
RNA
Polymerase II
RNA synthesisTranscription
Initiation complex
Chromatin changes
Transcription
RNA processing
mRNA
degradation
Translation
Protein processing
and degradation
A DNA-bending protein
brings the bound activators
closer to the promoter.
Other transcription factors,
mediator proteins, and RNA
polymerase are nearby.
2
Activator proteins bind
to distal control elements
grouped as an enhancer in
the DNA. This enhancer has
three binding sites.
1
The activators bind to
certain general transcription
factors and mediator
proteins, helping them form
an active transcription
initiation complex on the promoter.
3
Video Clip
• An activator
– Is a protein that binds to an enhancer and
stimulates transcription of a gene
Figure 19.6

• Some specific transcription factors function as
repressors
– To inhibit expression of a particular gene
• Some activators and repressors
– Act indirectly by influencing chromatin
structure

• Cancer results from genetic changes that affect
cell cycle control
• The gene regulation systems that go wrong
during cancer
– Turn out to be the very same systems that play
important roles in embryonic development

Types of Genes Associated with Cancer
• The genes that normally regulate cell growth
and division during the cell cycle
– Include genes for growth factors, their
receptors, and the intracellular molecules of
signaling pathways

Oncogenes and Proto-Oncogenes
• Oncogenes
– Are cancer-causing genes
• Proto-oncogenes
– Are normal cellular genes that code for
proteins that stimulate normal cell growth and
division

• A DNA change that makes a proto-oncogene
excessively active
– Converts it to an oncogene, which may promote
excessive cell division and cancer
Figure 19.11
Proto-oncogene
DNA
Translocation or transposition:
gene moved to new locus,
under new controls
Gene amplification:
multiple copies of the gene
Point mutation
within a control
element
Point mutation
within the gene
OncogeneOncogene
Normal growth-stimulating
protein in excess
Hyperactive or
degradation-
resistant protein
protein in excess
protein in excess
New
promoter

• The p53 gene encodes a tumor-suppressor
protein
– That is a specific transcription factor that
promotes the synthesis of cell cycle–inhibiting
proteins
Figure 19.12b
UV
light
DNA
Defective or
missing
transcription
factor, such as
p53, cannot
activate
transcription
MUTATION
Protein that
inhibits
the cell cycle
pathway, DNA damage is an intracellular
signal that is passed via protein kinases
and leads to activation of p53. Activated
p53 promotes transcription of the gene for a
protein that inhibits the cell cycle. The
resulting suppression of cell division ensures
that the damaged DNA is not replicated.
Mutations causing deficiencies in any
pathway component can contribute to the
development of cancer.
(b) Cell cycle–inhibiting pathway. In this
1
3
2
Protein kinases2
3 Active
form
of p53
DNA damage
in genome
1

• Mutations that knock out the p53 gene
– Can lead to excessive cell growth and cancer
Figure 19.12c
EFFECTS OF MUTATIONS
Protein
overexpressed
Cell cycle
overstimulated
Increased cell
division
Cell cycle not
inhibited
Protein absent
Effects of mutations. Increased
cell division, possibly leading to
cancer, can result if the cell cycle is
overstimulated, as in (a), or not
inhibited when it normally would be,
as in (b).
(c)

The Multistep Model of Cancer Development
• Normal cells are converted to cancer cells
– By the accumulation of multiple mutations
affecting proto-oncogenes and tumor-
suppressor genes

• A multistep model for the development of
colorectal cancer
Figure 19.13
Colon
Colon wall
Normal colon
epithelial cells
Small benign
growth (polyp)
Larger benign
growth (adenoma)
Malignant tumor
(carcinoma)
2 Activation of
ras oncogene
3 Loss of
tumor-
suppressor
gene DCC
4 Loss of
tumor-suppressor
gene p53
5 Additional
mutations
1 Loss of tumor-
suppressor
gene APC (or
other)

• Certain viruses
– Promote cancer by integration of viral DNA into
a cell’s genome
• Individuals who inherit a mutant oncogene or
tumor-suppressor allele
– Have an increased risk of developing certain
types of cancer

• Eukaryotic genomes can have many
noncoding DNA sequences in addition to
genes
• The bulk of most eukaryotic genomes
– Consists of noncoding DNA sequences, often
described in the past as “junk DNA”
• However, much evidence is accumulating
– That noncoding DNA plays important roles in
the cell (Probably is no such thing as ‘junk
DNA’)

The Relationship Between Genomic Composition
and Organismal Complexity
• Compared with prokaryotic genomes, the
genomes of eukaryotes
– Generally are larger
– Have longer genes
– Contain a much greater amount of noncoding
DNA both associated with genes and between
genes

Transposable Elements and Related Sequences
• The first evidence for wandering DNA
segments
– Came from geneticist Barbara McClintock’s
breeding experiments with Indian corn
Figure 19.15

Transposon
New copy of
transposon
Transposon
is copied
DNA of genome
Insertion
Mobile transposon
(a) Transposon movement (“copy-and-paste” mechanism)
Retrotransposon
New copy of
retrotransposon
DNA of genome
RNA
Reverse
transcriptase
(b) Retrotransposon movement
Insertion
Movement of Transposons and Retrotransposons
• Eukaryotic transposable elements are of two types
– Transposons, which move within a genome by
means of a DNA intermediate
– Retrotransposons, which move by means of an
RNA intermediate
Figure 19.16a, b

Sequences Related to Transposable Elements
• Multiple copies of transposable elements and
sequences related to them
– Are scattered throughout the eukaryotic
genome
• In humans
– A large portion of transposable element–
related DNA consists of a family of similar
sequences called Alu elements

Other Repetitive DNA, Including Simple Sequence DNA
• Simple sequence DNA
– Contains many copies of tandemly repeated
short sequences
– Is common in centromeres and telomeres,
where it probably plays structural roles in the
chromosome

Genes and Multigene Families
• Most eukaryotic genes
– Are present in one copy per haploid set of
chromosomes
• The rest of the genome
– Occurs in multigene families, collections of
identical or very similar genes

DNA RNA transcripts
Non-transcribed
spacer Transcription unit
DNA
18S 5.8S 28S
rRNA
5.8S
28S
18S
• Some multigene families
– Consist of identical DNA sequences, usually
clustered tandemly, such as those that code
for RNA products
Figure 19.17a Part
of the ribosomal
RNA gene family

• The classic examples of multigene families of
nonidentical genes
– Are two related families of genes that encode
globins
Figure 19.17b The human
-globin and -globin
gene families
-Globin
Heme
Hemoglobin
-Globin
-Globin gene family -Globin gene family
Chromosome 16 Chromosome 11
Embryo
Fetus
and adult Embryo Fetus Adult
 G
A
    
2
1
2 1


• Duplications, rearrangements, and mutations
of DNA contribute to genome evolution
• The basis of change at the genomic level is
mutation
– Which underlies much of genome evolution
Does the following produce new and novel
information?

Duplication of Chromosome Sets
• Accidents in cell division
– Can lead to extra copies of all or part of a
genome, which may then diverge if one set
accumulates sequence changes

Duplication and Divergence of DNA Segments
• Unequal crossing over during prophase I of
meiosis
– Can result in one chromosome with a deletion and
another with a duplication of a particular gene
Figure 19.18
Nonsister
chromatids
Transposable
element
Gene
Incorrect pairing
of two homologues
during meiosis
Crossover
and

Rearrangements of Parts of Genes: Exon
Duplication and Exon Shuffling
• A particular exon within a gene
– Could be duplicated on one chromosome and
deleted from the homologous chromosome

• In exon shuffling
– Errors in meiotic recombination lead to the
occasional mixing and matching of different exons
either within a gene or between two nonallelic
genes
Figure 19.20
EGF EGF EGF EGF
Epidermal growth
factor gene with multiple
EGF exons (green)
F F F F
Fibronectin gene with multiple
“finger” exons (orange)
Exon
shuffling
Exon
duplication
Exon
shuffling
K
F EGF K K
Plasminogen gene with a
“kfingle” exon (blue)
Portions of ancestral genes TPA gene as it exists today

How Transposable Elements Contribute to Genome Evolution
• Movement of transposable elements or
recombination between copies of the same
element
– Occasionally generates new sequence
combinations that are beneficial to the
organism (however, no new information was
added)
• Some mechanisms
– Can alter the functions of genes or their
patterns of expression and regulation

Prokaryotic eukaryoticgenome

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