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Eukaryotic Genomes:
Organization, Regulation, and
Evolution
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Figure 19.1
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Both prokaryotes and eukaryotes
– Must alter their patterns of gene expression in
response to changes in environmental
conditions
• Eukaryotic chromosomes
– Contain an enormous amount of DNA relative
to their condensed length
His- Histone
tones tails
Histone H1 10 nm
Figure 19.2 a
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Higher Levels of DNA Packing
• The next level of packing
– Forms the 30-nm chromatin fiber
30 nm
Nucleosome
Figure 19.2 b
300 nm Scaffold
Figure 19.2 c
700 nm
1,400 nm
Figure 19.2 d
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In interphase cells
– Most chromatin is in the highly extended form
called euchromatin
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
Figure 19.3
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Regulation of Chromatin Structure
• Genes within highly packed heterochromatin
– Are usually not expressed
Transcription
RNA processing
mRNA Translation
degradation
Protein processing
and degradation
Histone
tails
DNA
double helix
Amino acids
available
for chemical
modification
Upstream Downstream
Promoter Transcription Poly-A
signal
Primary RNA Exon Intron Exon Intron Exon Cleared 3′ end
transcript 5′ of primary
Chromatin changes
(pre-mRNA) transport
RNA processing:
Transcription Cap and tail added;
introns excised and
Intron RNA exons spliced together
RNA processing
Protein processing
and degradation mRNA G P P P
Enhancer TATA
box General
1 Activator proteins bind
to distal control elements transcription
grouped as an enhancer in factors
the DNA. This enhancer has DNA-bending
three binding sites. protein
2 A DNA-bending protein Group of
brings the bound activators Mediator proteins
closer to the promoter.
Other transcription factors, RNA
mediator proteins, and RNA Polymerase II
polymerase are nearby.
Chromatin changes
Protein processing
initiation complex on the promoter. and degradation
Control Albumin
elements gene
Crystallin
gene
Liver cell Lens cell
nucleus nucleus
Available Available
activators activators
Albumin
Albumin gene not
gene expressed
expressed
Transcription
RNA processing
mRNA Translation
degradation
Protein processing
and degradation
Exons
DNA
Primary
RNA
transcript
RNA splicing or
Chromatin changes
Transcription
RNA processing
mRNA Translation
degradation
complex
Dicer
Degradation of mRNA
OR
miRNA
Target mRNA
Transcription
RNA processing
Ubiquitin Proteasome
Translation
mRNA
degradation and ubiquitin
to be recycled
Protein processing Proteasome
and degradation
Figure 19.10
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Concept 19.3: 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
• Proto-oncogenes
– Are normal cellular genes that code for
proteins that stimulate normal cell growth and
division
DNA
Figure 19.11
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Tumor-Suppressor Genes
• Tumor-suppressor genes
– Encode proteins that inhibit abnormal cell
division
DNA
Gene expression
Protein that
stimulates
the cell cycle
Figure 19.12a
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• The p53 gene encodes a tumor-suppressor
protein
– That is a specific transcription factor that
promotes the synthesis of cell cycle–inhibiting
proteins
(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 2 Protein kinases MUTATION
p53 promotes transcription of the gene for a
Defective or
protein that inhibits the cell cycle. The
missing
resulting suppression of cell division ensures
transcription
that the damaged DNA is not replicated.
factor, such as
Mutations causing deficiencies in any
UV p53, cannot
pathway component can contribute to the 3 Active
light activate
development of cancer. form transcription
of p53
1 DNA damage
DNA
in genome
Protein that
inhibits
the cell cycle
Figure 19.12b
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Mutations that knock out the p53 gene
– Can lead to excessive cell growth and cancer
Figure 19.12c
1 Loss of tumor-
suppressor 4 Loss of
Colon wall gene APC (or 2 Activation of tumor-suppressor
other) ras oncogene gene p53
3 Loss of 5 Additional
tumor- mutations
Normal colon Small benign suppressor Larger benign Malignant tumor
epithelial cells growth (polyp) gene DCC growth (adenoma) (carcinoma)
Figure 19.13
Repetitive
DNA that
includes Introns and
transposable regulatory
elements sequences
and related (24%)
sequences
(44%)
Unique
noncoding
Repetitive DNA (15%)
DNA
unrelated to
transposable
elements
Alu elements
(about 15%)
(10%)
Simple sequence
Large-segment
Figure 19.14 DNA (3%)
duplications (5-6%)
Figure 19.15
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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
New copy of
Transposon transposon
DNA of genome
Transposon
is copied Insertion
Mobile transposon
(a) Transposon movement (“copy-and-paste” mechanism)
New copy of
Retrotransposon retrotransposon
DNA of genome
RNA
Reverse Insertion
transcriptase
Non-transcribed
spacer Transcription unit
DNA
18S 5.8S 28S
rRNA
5.8S
Figure 19.17a Part 28S
of the ribosomal
RNA gene family 18S
Hemoglobin
α-Globin
Chromosome 16 Chromosome 11
ζ ψζ ψ ψα α2 α1 ψℑ ∈ Gγ Aγ ψβ δ β
α 21
Nonsister
chromatids
Crossover
Incorrect pairing
of two homologues
during meiosis
and
Figure 19.18
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Evolution of Genes with Related Functions: The
Human Globin Genes
• The genes encoding the various globin proteins
– Evolved from one common ancestral globin gene,
which duplicated and diverged
Ancestral globin gene
Duplication of
ancestral gene
Evolutionary time
Mutation in
both copies α β
Transposition to
different chromosomes
Further duplications α β
and mutations
ζ α ∈ γ β
ζ ψ ζ ψ α ψ α α2 α1 ψ θ ∈ Gγ Aγ ψβ δ β
2 1
α-Globin gene family β -Globin gene family
Figure 19.19 on chromosome 16 on chromosome 11
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Subsequent duplications of these genes and
random mutations
– Gave rise to the present globin genes, all of
which code for oxygen-binding proteins
Table 19.1
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Evolution of Genes with Novel Functions
• The copies of some duplicated genes
– Have diverged so much during evolutionary
time that the functions of their encoded
proteins are now substantially different
K
Plasminogen gene with a Exon
“kfingle” exon (blue) shuffling
• Some mechanisms
– Can alter the functions of genes or their
patterns of expression and regulation