Download Figure 19.5 A eukaryotic gene and its transcript

Chapter 19
Eukaryotic Genomes
Organization, Regulation, and
Evolution
PowerPoint TextEdit Art Slides for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 19.1 DNA in a eukaryotic chromosome from a
developing salamander egg
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Figure 19.2 Levels of chromatin packing
2 nm
DNA double helix
Histones
Histone
tails
Histone H1
Linker DNA
(“string”)
10 nm
Nucleosome
(“bad”)
(a) Nucleosomes (10-nm fiber)
30 nm
Nucleosome
(b) 30-nm fiber
Protein scaffold
Loops
300 nm
(c) Looped domains (300-nm fiber)
700 nm
1,400 nm
(d) Metaphase chromosome
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Scaffold
Figure 19.3 Stages in gene expression that can be
regulated in eukaryotic cells
Signal
NUCLEUS
Chromatin
Chromatin modification:
DNA unpacking involving
histone acetylation and
DNA demethlation
DNA
Gene available
for transcription
Gene
Transcription
RNA
Exon
Primary transcript
Intron
RNA processing
Tail
Cap
mRNA in nucleus
Transport to cytoplasm
CYTOPLASM
mRNA in cytoplasm
Degradation
of mRNA
Translation
Polypetide
Cleavage
Chemical modification
Transport to cellular
destination
Active protein
Degradation of protein
Degraded protein
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Figure 19.4 A simple model of histone tails and the
effect of histone acetylation
Chromatin changes
Transcription
RNA processing
mRNA
degradation
Translation
Protein processing
and degradation
Histone
tails
DNA
double helix
Amino acids
available
for chemical
modification
(a) Histone tails protrude outward from a nucleosome
Unacetylated histones
Acetylated histones
(b) Acetylation of histone tails promotes loose chromatin
structure that permits transcription
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Figure 19.5 A eukaryotic gene and its transcript
Enhancer
(distal control elements)
Poly-A signal
sequence
Proximal
control elements
Exon
Intron
Exon
Intron
Termination
region
Exon
DNA
Downstream
Upstream
Promoter
Chromatin changes
Transcription
Exon
Primary RNA
5
transcript
(pre-mRNA)
Intron
mRNA
degradation
Intron RNA
Exon
Cleared 3 end
of primary
transport
Coding segment
Translation
Protein processing
and degradation
Intron
RNA processing:
Cap and tail added;
introns excised and
exons spliced together
Transcription
RNA processing
Exon
Poly-A
signal
mRNA
G
P
P
5 Cap
P
5 UTR
(untranslated
region)
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Start
codon
Stop
codon
Poly-A
3 UTR
(untranslated tail
region)
Figure 19.6 A model for the action of enhancers
and transcription activators
Distal control
element
Activators
Enhancer
1 Activator proteins bind
to distal control elements
grouped as an enhancer in
the DNA. This enhancer has
three binding sites.
Promoter
Gene
TATA
box
General
transcription
factors
DNA-bending
protein
2 A DNA-bending protein
brings the bound activators
closer to the promoter.
Other transcription factors,
mediator proteins, and RNA
polymerase are nearby.
Group of
Mediator proteins
RNA
Polymerase II
Chromatin changes
3 The activators bind to
certain general transcription
factors and mediator
proteins, helping them form
an active transcription
initiation complex on the promoter.
Transcription
RNA processing
mRNA
degradation
RNA
Polymerase II
Translation
Protein processing
and degradation
Transcription
Initiation complex
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RNA synthesis
Figure 19.7 Cell type–specific transcription
Enhancer Promoter
Albumin
gene
Control
elements
Crystallin
gene
Liver cell
nucleus
Available
activators
Lens cell
nucleus
Available
activators
Albumin
gene not
expressed
Albumin
gene
expressed
Crystallin gene
not expressed
(a) Liver cell
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Crystallin gene
expressed
(b) Lens cell
Figure 19.8 Alternative RNA splicing
Chromatin changes
Transcription
RNA processing
mRNA
degradation
Translation
Protein processing
and degradation
Exons
DNA
Primary
RNA
transcript
RNA splicing
mRNA
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or
Figure 19.9 Regulation of gene expression by
microRNAs (miRNAs)
1 The microRNA (miRNA)
precursor folds
back on itself,
held together
by hydrogen
bonds.
2 An enzyme
called Dicer moves
along the doublestranded RNA,
cutting it into
shorter segments.
3 One strand of
each short doublestranded RNA is
degraded; the other
strand (miRNA) then
associates with a
complex of proteins.
4 The bound
miRNA can base-pair
with any target
mRNA that contains
the complementary
sequence.
5 The miRNA-protein
complex prevents gene
expression either by
degrading the target
mRNA or by blocking
its translation.
Chromatin changes
Transcription
RNA processing
mRNA
degradation
Translation
Protein processing
and degradation
Protein
complex
Dicer
Degradation of mRNA
OR
miRNA
Target mRNA
Hydrogen
bond
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Blockage of translation
Figure 19.10 Degradation of a protein by a
proteasome
Chromatin changes
1 Multiple ubiquitin molecules are attached to a protein
by enzymes in the cytosol.
2 The ubiquitin-tagged protein
is recognized by a proteasome,
which unfolds the protein and
sequesters it within a central cavity.
2 Enzymatic components of the
proteasome cut the protein into
small peptides, which can be
further degraded by other
enzymes in the cytosol.
Transcription
RNA processing
mRNA
degradation
Proteasome
and ubiquitin
to be recycled
Ubiquitin
Translation
Proteasome
Protein processing
and degradation
Protein to
be degraded
Ubiquinated
protein
Protein entering a
proteasome
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Protein
fragments
(peptides)
Figure 19.11 Genetic changes that can turn
proto-oncogenes into oncogenes
Proto-oncogene
DNA
Translocation or transposition:
gene moved to new locus,
under new controls
Gene amplification:
multiple copies of the gene
New
promoter
Normal growth-stimulating
protein in excess
Normal growth-stimulating
protein in excess
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Point mutation
within a control
element
Point mutation
within the gene
Oncogene
Oncogene
Normal growth-stimulating
protein in excess
Hyperactive or
degradationresistant protein
Figure 19.12 Signaling pathways that regulate cell
division
1 Growth
factor
(a) Cell cycle–stimulating pathway.
This pathway is triggered by 1 a growth
factor that binds to 2 its receptor in the
plasma membrane. The signal is relayed to 3
a G protein called Ras. Like all G proteins, Ras
is active when GTP is bound to it. Ras passes
the signal to 4 a series of protein kinases.
The last kinase activates 5 a transcription
activator that turns on one or more genes
for proteins that stimulate the cell cycle. If a
mutation makes Ras or any other pathway
component abnormally active, excessive cell
division and cancer may result.
Ras
3 G protein
GTP
Ras
p
p
p
2 Receptor
p
p
p
GTP
MUTATION
Hyperactive
Ras protein
(product of
oncogene)
issues signals
on its own
4 Protein kinases
(phosphorylation
cascade)
NUCLEUS
5 Transcription
factor (activator)
DNA
Gene expression
Protein that
stimulates
the cell cycle
(b) Cell cycle–inhibiting pathway. In this
pathway, 1 DNA damage is an intracellular
signal that is passed via 2 protein kinases
and leads to activation of 3 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.
2 Protein kinases
UV
light
3 Active
1 DNA damage
in genome
form
of p53
MUTATION
Defective or
missing
transcription
factor, such as
p53, cannot
activate
transcription
DNA
Protein that
inhibits
the cell cycle
(c) 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).
EFFECTS OF MUTATIONS
Protein
overexpressed
Cell cycle
overstimulated
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Protein absent
Increased cell
division
Cell cycle not
inhibited
Figure 19.13 A multistep model for the development
of colorectal cancer
Colon
Colon wall
Normal colon
epithelial cells
4 Loss of
tumor-suppressor
gene p53
2 Activation of
Ras oncogene
1 Loss of
tumor-suppressor
gene APC (or
other)
Small benign
growth (polyp)
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3 Loss of
tumorsuppressor
gene DCC
5 Additional
mutations
Larger benign
growth (adenoma)
Malignant tumor
(carcinoma)
Figure 19.14 Types of DNA sequences in the
human genome
Exons (regions of genes coding
for protein, rRNA, tRNA) (1.5%)
Repetitive
DNA that
includes
transposable
elements
and related
sequences
(44%)
Introns and
regulatory
sequences
(24%)
Repetitive
DNA
unrelated to
transposable
elements
(about 15%)
Alu elements
(10%)
Simple sequence
DNA (3%)
Large-segment
duplications (5–6%)
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Unique
noncoding
DNA (15%)
Figure 19.15 The effect of transposable elements on
corn kernel color
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Figure 19.16 Movement of eukaryotic transposable
elements
Transposon
DNA of genome
Transposon
is copied
New copy of
transposon
Insertion
Mobile transposon
(a) Transposon movement (“copy-and-paste” mechanism)
New copy of
Retrotransposon
retrotransposon
DNA of genome
RNA
Reverse
transcriptase
(b) Retrotransposon movement
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Insertion
Figure 19.17 Gene families
DNA
RNA transcripts
Non-transcribed
spacer
Transcription unit
DNA
18S
28S
5.8S
rRNA
5.8S
28S
18S
(a) Part of the ribosomal RNA gene family
-Globin
Heme
Hemoglobin
-Globin
-Globin gene family
-Globin gene family
Chromosome 16
Chromosome 11

 2  1 2 1 
Embryo
Fetus
and adult

Embryo
G A 


Fetus
Adult
(b) The human -globin and -globin gene families
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Figure 19.18 Gene duplication due to unequal
crossing over
Transposable
element
Gene
Nonsister
chromatids
Crossover
Incorrect pairing
of two homologues
during meiosis
and
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Figure 19.19 Evolution of the human -globin and
-globin gene families
Ancestral globin gene
Duplication of
ancestral gene
Mutation in
both copies


Transposition to
different chromosomes


Further duplications
and mutations



  

2 1 
-Globin gene family
on chromosome 16
2
1
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


G

A

 -Globin gene family
on chromosome 11


Table 19.1 Percentage of Similarity in Amino Acid
Sequence Between Human Globin Proteins
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Figure 19.20 Evolution of a new gene by exon shuffling
EGF
EGF
EGF
EGF
Epidermal growth
factor gene with multiple
EGF exons (green)
Exon
shuffling
F
F
F
Exon
duplication
F
Fibronectin gene with multiple
“finger” exons (orange)
F
EGF
K
K
Plasminogen gene with a
“kringle” exon (blue)
Portions of ancestral genes
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Exon
shuffling
TPA gene as it exists today
K