Download AP Biology PowerPoint Ch 19

Chapter 19
The Organization
and Control of
Eukaryotic Genomes
Human Genome
3
billion base pairs.
30,000 to 50,000 genes.
3%-5% active at any moment.
Questions?
With
so much DNA in a cell,
how is it organized or
packaged?
How is the expression of the
DNA controlled?
Movie – DNA Packaging
Microscopic Levels
1.
2.
3.
4.
Nucleosomes
30-nm Chromatin Fibers
Looped Domains
Chromosomes
Nucleosomes
"Beads
on a String”.
DNA wound on a protein core.
Packaging for DNA.
Controls transcription.
Protein Core
Two
molecules of four types
of Histone proteins.
H1- 5th type of Histone
protein attaches the DNA to
the outside of the core.
30 - nm
Chromatin Fibers
A
cylinder of tightly coiled
nucleosomes 30 - nm in
diameter.
Looped Domains
Loops
of 30 - nm chromatin.
Protein Scaffold
Chromosomes
Large
units of DNA.
Similar to "Chapters" in the
Book of Life.
Chromosome Regions
1. Heterochromatin - highly
condensed chromatin;
areas that are not transcribed.
2. Euchromatin - less condensed
chromatin; areas of active
transcription.
Molecular Level
Organization
1. Repetitive Sequences
2. Satellite DNA
3. Interspersed Repetitive DNA
4. Multigene Families
Repetitive Sequences
Tandemly
repeating units of
1-10 nucleotides.
10% to 15% of total DNA.
Satellite DNA
Repetitive
areas of DNA
found at the:
Tips
of chromosomes.
Centromere regions.
Structural
DNA.
Result
Give
regions of the DNA
different densities.
Linked to some genetic
disorders.
Ex.
- Fragile X Syndrome
Huntington’s disease
Interspersed
Repetitive DNA
25
- 40% of DNA
Copies of repetitive units that
are scattered among genes.
Often transcribed,
but function not clear.
Multigene Families
A
collection of identical or
very similar genes.
From a common ancestral
gene.
May be clustered or
dispersed in the genome.
Identical Families
Identical
genes for the same
protein.
Ex: Ribosomal Protein and
rRNA.
Result - Many copies of
ribosomes possible.
Most common gene in DNA.
Identical Genes
Nonidentical Families
Related
clusters of genes
that are nearly identical in
their base sequences.
Ex: Globin Genes
Globin Gene Evolution
a - Globin Family
Found
on chromosome 16.
Contains two copies of
a globin, one fetal globin and
four pseudogenes.
b - Globin Family
Found
on chromosome 11.
Contains two copies of
b globin, one embryo, two
fetal and one pseudogene.
Pseudogene
Gene
with sequences very
similar to real genes, but lack
promoter sites.
Are not transcribed into
proteins.
Possible proof of
transpositions ?
Genome Plasticity
Changes
in the ways a gene
can be expressed.
Seen only in somatic cells.
Have major effects on gene
expression within particular
cells and tissues.
Types
1. Gene Amplification
2. Selective Gene Loss
3. Genomic Rearrangements
Gene Amplification
The
selective replication of
certain genes.
Ex: rRNA genes in eggs
Result - many copies of rRNA
for making ribosomes.
Selective Gene Loss
Loss
of genes or
chromosomes in some
tissues during development.
Result - DNA (genes) lost and
not expressed.
Genomic
Rearrangements
Shuffling
of DNA areas
(not from Meiosis).
Ex: Transposons
retrotransposons
antibody genes.
Transposons - Example
Result
Genes
moved structurally
within the genome.
Transcription control
changed.
Control of Gene
Expression
Complicated
Process.
Many levels of control are
possible.
Main Control Levels
1. Nucleus - those inside the
nuclear membrane.
2. Cytoplasm - those that
occur in the cytoplasm.
Nucleus Level
1.
2.
3.
4.
Extra-Cellular Signals
Chromatin Modifications
Transcriptional Control
Posttranscriptional Control
Extra-Cellular Signal
Signal
from outside the cells
(usually a hormone).
Review specifics from
Chapter 11.
Result - regions of DNA
activated for transcription.
Chromatin
Modifications
DNA
Methylation.
Histone Acetylation.
Gene rearrangements.
Gene amplification.
DNA Methylation
Addition
of methyl groups
(-CH3) to DNA bases.
Result - long-term shut-down
of DNA transcription.
Ex: Barr bodies
genomic imprinting
Histone Acetylation
Attachment
of acetyl groups
(-COCH3) to AAs in histones.
Result - DNA held less tightly
to the nucleosomes, more
accessible for transcription.
Transcriptional Control
Ex:
Enhancers,
DNA-Binding Domains
regulatory RNA.
Result - genes are more
(or less) available for
transcription.
Factors that affect the
transcription of genes.
Movie – Turning on a Gene
Enhancers
Areas
of DNA that increase
transcription.
May be widely separated
from the gene
(usually upstream).
DNA-Binding Domains
Proteins
that bind to DNA
and regulate transcription.
Ex:
Helix-turn-Helix
Zinc-Finger
Leucine
Zipper
DNA – Binding Domains
Regulatory RNA
Small
RNA molecules that are
not translated
Interact with DNA
Whole new area in gene
regulation
Posttranscriptional
Control
1. RNA Processing
Ex - introns and exons.
2. RNA Transport - moving the
mRNA into the cytoplasm.
3. RNA Degradation - breaking
down old mRNA.
Transcription Control
Movie – RNA processing
Cytoplasm Level of
Control
1. Translation
2. Polypeptide Changes
Movie – Translation control
Translation Control
Regulated
by the availability
of initiation factors.
Availability of tRNAs, AAs
and other protein synthesis
factors. (review Chapter 17).
Polypeptide Changes
Changes
to the protein
structure after translation.
Ex: Cleavage
Modifications
Activation
Transport
Degradation
Movie – Protein Processing
Protein Degradation
By
Proteosomes using
Ubiquitin to mark the protein.
Gene Expression
and Cancer
Cancer
- loss of the genetic
control of cell division.
Balance between growthstimulating pathway
(accelerator) and growthinhibiting pathway (brakes).
Proto-oncogenes
Normal
genes for cell growth and
cell division factors.
Genetic changes may turn them
into oncogenes (cancer genes).
Ex: Gene Amplification,
Translocations, Transpositions,
Point Mutations
Proto-oncogenes
Tumor-Suppressor
Genes
Genes
that inhibit cell
division.
Ex - p53, p21
Cancer Examples
RAS
- a G protein.
When mutated, causes an
increase in cell division by
over-stimulating protein
kinases.
Several mutations known.
Cancer Examples
p53
- involved with several
DNA repair genes and
“checking” genes.
When damaged, can’t inhibit
cell division or cause
damaged cells to apoptose.
Comment
p53
is known to be sensitive
to cigarette smoke.
Damage by smoke often
leads to lung cancer.
Over-activity of p53 causes
problems too.
Carcinogens
Agents
that cause cancer.
Ex: radiation, chemicals
Most work by altering the
DNA, or interfering with
control or repair
mechanisms.
Multiple Hit Hypothesis
Cancer
is the result of
several control mechanisms
breaking down.
Ex: Colorectal Cancer
requires 4 to 5 mutations
before cancer starts.
Colorectal Cancer
Summary
DNA
packaging and gene
expression are very complex
with lots of opportunities for
control points.
Be able to discuss how DNA
is organized and packed.
Summary
Be
able to discuss
mechanisms for regulating
DNA and protein synthesis
(know several ways)
How control of DNA can lead
to cancer.