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Students-Get handout - FRQs
-Pull out Learning Logs for check
-Thursday – Test – Learning logs due
-Friday – Test corrections
-Cell phones in bins….off or muted…please & thank you
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?
2 nm
10 nm
DNA double helix
Histonetails
His-tones
Linker DNA(“string”)
Nucleosome(“bead”)
Histone H1
(a) Nucleosomes (10-nm fiber)
Nucleosome
Protein scaffold
30 nm
300 nm
700 nm
1,400 nm
(b) 30-nm fiber
(c) Looped domains (300-nm fiber)
(d) Metaphase chromosome
Loops
Scaffold
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?
- DNA level – Chromatin changes- DNA demethylation
- Histone acetylation
Signal
NUCLEUS
Chromatin
Chromatin modification:DNA unpacking involvinghistone acetylation and
DNA demethlation
Gene
DNAGene availablefor transcription
RNA Exon
Transcription
Primary transcript
RNA processing
Transport to cytoplasm
Intron
Cap mRNA in nucleus
Tail
CYTOPLASM
mRNA in cytoplasm
Degradationof mRNA
Translation
Polypetide
CleavageChemical modificationTransport to cellular
destination
Active protein
Degradation of protein
Degraded protein
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?
- DNA level – Chromatin changes- DNA demethylation
- 5% of Cytosines have –CH3
- Demethylase removes –CH3
- Histone acetylation
Chromatin changes
Transcription
RNA processing
mRNA degradation
Translation
Protein processingand degradation
Histonetails
DNAdouble helix Amino acids
availablefor chemicalmodification
(a) Histone tails protrude outward from a nucleosome
(b) Acetylation of histone tails promotes loose chromatinstructure that permits transcription
Unacetylated histones Acetylated histones
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?
- DNA level – Chromatin changes- DNA demethylation- Histone acetylation
- RNA level- Activation of transcription
Signal
NUCLEUS
Chromatin
Chromatin modification:DNA unpacking involvinghistone acetylation and
DNA demethlation
Gene
DNAGene availablefor transcription
RNA Exon
Transcription
Primary transcript
RNA processing
Transport to cytoplasm
Intron
Cap mRNA in nucleus
Tail
CYTOPLASM
mRNA in cytoplasm
Degradationof mRNA
Translation
Polypetide
CleavageChemical modificationTransport to cellular
destination
Active protein
Degradation of protein
Degraded protein
Enhancer(distal control elements)
Proximalcontrol elements
DNA
UpstreamPromoter
Exon Intron Exon Intron
Poly-A signalsequence
Exon
Terminationregion
Transcription
Downstream
Poly-Asignal
ExonIntronExonIntronExonPrimary RNAtranscript(pre-mRNA)
5
Intron RNA
RNA processing:Cap and tail added;introns excised andexons spliced together
Coding segment
P P PGmRNA
5 Cap 5 UTR(untranslated
region)
Startcodon
Stopcodon
3 UTR(untranslatedregion)
Poly-Atail
Chromatin changes
Transcription
RNA processing
mRNAdegradation
Translation
Protein processingand degradation
Cleared 3 endof primarytransport
Figure 19.5 A eukaryotic gene and its transcript
-Proximal and distal control elements farther upstream from promoter-Enhancers (activators) or silencers may bind here
Distal controlelement
Activators
Enhancer
PromoterGene
TATAbox
Generaltranscriptionfactors
DNA-bendingprotein
Group ofMediator proteins
RNAPolymerase II
RNAPolymerase II
RNA synthesisTranscriptionInitiation complex
Chromatin changes
Transcription
RNA processing
mRNAdegradation
Translation
Protein processingand degradation
A DNA-bending proteinbrings the bound activators
closer to the promoter.Other transcription factors,
mediator proteins, and RNApolymerase are nearby.
2
Activator proteins bindto distal control elementsgrouped as an enhancer in the DNA. This enhancer hasthree binding sites.
1
The activators bind tocertain general transcription
factors and mediatorproteins, helping them form
an active transcriptioninitiation complex on the promoter.
3
Figure 19.6 A model for the action of enhancers and transcription activators
Why is this relevant??Who cares??
All somatic cells have the same DNA so…
Enhancer Promoter
Controlelements
Albumingene
Crystallingene
Liver cellnucleus
Lens cellnucleus
Availableactivators
Availableactivators
Albumingeneexpressed
Albumingene notexpressed
Crystallin genenot expressed
Crystallin geneexpressed
Liver cell Lens cell(a) (b)
How is cell-specific transcription controlled?
-cell-specific activators
-Non-active genes are heavily methylated
Students-Thursday – Test – Learning logs due
-Friday – Test corrections
-Career Center cancer student -Chick-fil-A on Peter’s Creek Thursday from 11am – 7pm -Donating 15% of all sales
-Friday is transport
-Parent survey on CC website
-Phones in bin….off or muted…please & thank you
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?
- DNA level- DNA demethylation- Histone acetylation
- RNA level- Activation of transcription- RNA processing
- 5’ cap & 3’ poly-A tail- Alternative splicing- 75% of human genes
- mRNA transport to cytoplasm- mRNA degradation
Chromatin changes
Transcription
RNA processing
mRNAdegradation
Translation
Protein processingand degradation
Exons
DNA
PrimaryRNAtranscript
mRNA
RNA splicing or
Chromatin changes
Transcription
RNA processing
mRNAdegradation
Translation
Protein processingand degradation
Degradation of mRNAOR
Blockage of translation
Target mRNA
miRNA
Proteincomplex
Dicer
Hydrogenbond
The micro-RNA (miRNA)precursor foldsback on itself,held togetherby hydrogenbonds.
1 An enzymecalled Dicer movesalong the double-stranded RNA, cutting it intoshorter segments.
2 One strand ofeach short double-stranded RNA isdegraded; the otherstrand (miRNA) thenassociates with acomplex of proteins.
3 The boundmiRNA can base-pairwith any targetmRNA that containsthe complementarysequence.
4 The miRNA-proteincomplex prevents geneexpression either bydegrading the targetmRNA or by blockingits translation.
5
Figure 19.9 Regulation of gene expression by microRNAs (miRNAs)
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?
- DNA level- DNA demethylation- Histone acetylation
- RNA level- Activation of transcription- RNA processing- mRNA transport to cytoplasm- mRNA degradation
- Protein level- Translation - Cleavage
- signal peptide - Inactive “-ogen” proteins
- Chemical modification – Carbs, lipids- Transport to organelles- Protein degradation
Signal
NUCLEUS
Chromatin
Chromatin modification:DNA unpacking involvinghistone acetylation and
DNA demethlation
Gene
DNAGene availablefor transcription
RNA Exon
Transcription
Primary transcript
RNA processing
Transport to cytoplasm
Intron
Cap mRNA in nucleus
Tail
CYTOPLASM
mRNA in cytoplasm
Degradationof mRNA
Translation
Polypetide
CleavageChemical modificationTransport to cellular
destination
Active protein
Degradation of protein
Degraded protein
Chromatin changes
Transcription
RNA processing
mRNAdegradation
Translation
Protein processingand degradation
Ubiquitin
Protein tobe degraded
Ubiquinatedprotein
Proteasome
Proteasomeand ubiquitinto be recycled
Proteinfragments(peptides)
Multiple ubiquitin mol-ecules are attached to a proteinby enzymes in the cytosol.
1 The ubiquitin-tagged proteinis recognized by a proteasome,which unfolds the protein andsequesters it within a central cavity.
2 Enzymatic components of theproteasome cut the protein intosmall peptides, which can befurther degraded by otherenzymes in the cytosol.
2
Protein entering aproteasome
Figure 19.10 Degradation of a protein by a proteasome
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?3. How can proto-oncogenes become oncogenes?
Proto-oncogene
DNA
Translocation or transposition:gene moved to new locus,under new controls
Gene amplification:multiple copies of the gene
Point mutationwithin a controlelement
Point mutationwithin the gene
OncogeneOncogene
Normal growth-stimulatingprotein in excess
Hyperactive ordegradation-resistant protein
Normal growth-stimulatingprotein in excess
Normal growth-stimulatingprotein in excess
Newpromoter
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?3. How can proto-oncogenes become oncogenes?4. How can disruptions of cell growth pathways lead to cancer?
1 Growthfactor MUTATION
2 Receptor
ppp p
pp
GTP
Ras
3 G protein
Ras
GTP
HyperactiveRas protein(product ofoncogene)issues signalson its own
4 Protein kinases(phosphorylationcascade)
5 Transcriptionfactor (activator)
NUCLEUS
DNA
Gene expression
Protein thatstimulatesthe cell cycle
2 Protein kinases
UVlight
DNA damagein genome
1
DNA
3 Activeformof p53
Defective ormissingtranscriptionfactor, such asp53, cannotactivatetranscription
MUTATION
Protein thatinhibitsthe cell cycle
EFFECTS OF MUTATIONS
Proteinoverexpressed
Cell cycleoverstimulated
Increased celldivision
Cell cycle notinhibited
Protein absent
(a) Cell cycle–stimulating pathway.This pathway is triggered by a growthfactor that binds to its receptor in theplasma membrane. The signal is relayed to a G protein called Ras. Like all G proteins, Rasis active when GTP is bound to it. Ras passesthe signal to a series of protein kinases.The last kinase activates a transcriptionactivator that turns on one or more genes for proteins that stimulate the cell cycle. If amutation makes Ras or any other pathway component abnormally active, excessive celldivision and cancer may result.
12
4
3
5
(b) Cell cycle–inhibiting pathway. In this
2pathway, DNA damage is an intracellularsignal that is passed via protein kinasesand leads to activation of p53. Activatedp53 promotes transcription of the gene for aprotein that inhibits the cell cycle. Theresulting suppression of cell division ensuresthat the damaged DNA is not replicated.Mutations causing deficiencies in anypathway component can contribute to thedevelopment of cancer.
1
3
(c) Effects of mutations. Increased cell division,possibly leading to cancer, can result if thecell cycle is overstimulated, as in (a), or notinhibited when it normally would be, as in (b).
Figure 19.12 Signaling pathways that regulate cell division
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?3. How can proto-oncogenes become oncogenes?4. How can disruptions of cell growth pathways lead to cancer?5. What are the differences between prokaryotic & eukaryotic DNA?
Prokaryotic EukaryoticNo introns Introns More mutations Few mutations (proofreading)Circular chromosome Several linear chromosomesNot in a nucleus In a nucleusCoupled transcription Separate transcription
& translation & translationMostly coding Mostly “filler”
Exons (regions of genes codingfor protein, rRNA, tRNA) (1.5%)
RepetitiveDNA thatincludestransposableelementsand relatedsequences(44%)
Introns andregulatorysequences(24%)
UniquenoncodingDNA (15%)
RepetitiveDNAunrelated totransposableelements(about 15%)
Alu elements(10%)
Simple sequenceDNA (3%)
Large-segmentduplications (5–6%)
Figure 19.14 Types of DNA sequences in the human genome
- Tandomly repetitive DNA (satellite DNA) – 15% - …GTTACGTTACGTTACGTTACGTTAC…- Found in telomeres & centromeres
- Interspersed repetitive DNA – 44%- repeats scattered throughout the genome
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?3. How can proto-oncogenes become oncogenes?4. How can disruptions of cell growth pathways lead to cancer?5. What are the differences between prokaryotic & eukaryotic DNA?6. How do eukaryotic transposable elements become repetitive?
TransposonNew copy oftransposon
Transposonis copied
DNA of genome
Insertion
Mobile transposon
(a) Transposon movement (“copy-and-paste” mechanism)
RetrotransposonNew copy of
retrotransposon
DNA of genome
RNA
Reversetranscriptase
(b) Retrotransposon movement
Insertion
Figure 19.16 Movement of eukaryotic transposable elements
Figure 19.15 The effect of transposable elements on corn kernel color
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution
1. How is chromatin structured on a chromosome?2. How is gene expression regulated?3. How can proto-oncogenes become oncogenes?4. How can disruptions of cell growth pathways lead to cancer?5. What are the differences between prokaryotic & eukaryotic DNA?6. How do eukaryotic transposable elements become repetitive?7. What are gene families?
- Collection of identical or very similar genes that are clustered or dispersed throughout the genome
DNA RNA transcripts
Non-transcribedspacer Transcription unit
DNA18S 5.8S 28S
rRNA5.8S
(a) Part of the ribosomal RNA gene family
28S
18S
Heme
Hemoglobin
-Globin
-Globin
-Globin gene family -Globin gene family
Chromosome 16 Chromosome 11
21
2 1 G A
EmbryoFetus
and adult Embryo Fetus Adult
(b) The human -globin and -globin gene families
Figure 19.17 Gene families
Eukaryotic version of an operon.- controlled by 1 promoter
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?3. How can proto-oncogenes become oncogenes?4. How can disruptions of cell growth pathways lead to cancer?5. What are the differences between prokaryotic & eukaryotic DNA?6. How do eukaryotic transposable elements become repetitive?7. What are gene families?8. How do genes get duplicated or deleted?
Figure 19.18 Gene duplication due to unequal crossing over
Nonsisterchromatids
Transposableelement
Gene
Incorrect pairingof two homologuesduring meiosis
Crossover
and
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?3. How can proto-oncogenes become oncogenes?4. How can disruptions of cell growth pathways lead to cancer?5. What are the differences between prokaryotic & eukaryotic DNA?6. How do eukaryotic transposable elements become repetitive?7. What are gene families?8. How do genes get duplicated or deleted?9. How did the globin gene family evolve?
Ancestral globin gene
21
2 1 G A
-Globin gene familyon chromosome 16
-Globin gene familyon chromosome 11
Evo
lutio
nary
tim
e
Duplication ofancestral gene
Mutation inboth copies
Transposition todifferent chromosomes
Further duplicationsand mutations
Figure 19.19 Evolution of the human -globin and -globin gene families
Chapter 19: Eukaryotic Genomes: Organization, Regulation & Evolution1. How is chromatin structured on a chromosome?2. How is gene expression regulated?3. How can proto-oncogenes become oncogenes?4. How can disruptions of cell growth pathways lead to cancer?5. What are the differences between prokaryotic & eukaryotic DNA?6. How do eukaryotic transposable elements become repetitive?7. What are gene families?8. How do genes get duplicated or deleted?9. How did the globin gene family evolve?10. How do new genes evolve?
- Exon shuffling
EGF EGF EGF EGF
Epidermal growthfactor gene with multipleEGF exons (green)
F F F F
Fibronectin gene with multiple“finger” exons (orange)
Exonshuffling
Exonduplication
Exonshuffling
K
F EGF K K
Plasminogen gene with a“kringle” exon (blue)
Portions of ancestral genes TPA gene as it exists today
Figure 19.20 Evolution of a new gene by exon shuffling
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