Title: Nerve activates contraction
1CHAPTER 19THE ORGANIZATION AND CONTROL OF
EUKARYOTIC GENOMES
- gt Larger than prokaryotes
- Not all 25,000 genes are active in all cells
2Junk DNA anyone?
- Prokaryotes- most of the DNA in a genome codes
for protein (or tRNA and rRNA), with a small
amount of noncoding DNA, primarily regulators. - Eukaryotes - most of the DNA (about 97 in
humans) does not code for protein or RNA.
- Only 25,000 genes in humans - 3 of total DNA in
cell (YIKES!) - Rest of it (97) - junk????? (noncoding DNA)
96 similar to humans)
3Noncoding DNA and what it does in the
eukaryotic genome
- 1) Some noncoding regions are regulatory
sequences (these are promotors and enhancers that
can increase binding of RNA polymerase to DNA). - 2) Other are introns.
- 3) Finally, even more of it consists of
repetitive DNA, present in many copies in the
genome.
4REPPPPETITIVE DNA IN EUKARYOTES
- Know 2 types of Repetitive DNA
- 1)TANDEMLY REPETITIVE DNA (AKA SATELLITE DNA - 3
types) - 10 to 15 of DNA - 2) INTERSPERSED REPETITIVE DNA - 25 - 40 of DNA
GTTACGTTACGTTAC.repeated 10 to 10 million times
(Satellite DNA)
5REPPPPETITIVE DNA IN EUKARYOTES
- 1) SATELLITE DNA/TANDEMLY REPETITIVE DNA
- These sequences (1 to 10 base pairs) are repeated
up to a million times in series. - GTTACGTTACGTTAC.
- 3 types
- a) Regular Satellite -100,000 - 10 mill
- b) Minisatellite -100 -100,000 repeats
- c) Microsatellite - 10 to 100 repeats -
- Very important for forensics - helps figure out
uniqueness of a persons DNA
6- A number of genetic disorders are caused by
abnormally long stretches of tandemly repeated
nucleotide triplets within the affected gene.
7(No Transcript)
8 9(No Transcript)
10You know that antisocial neighbor - May be a
microsatellite problem!
11- Satellite DNA plays a structural role at
telomeres and centromeres. This is important!
You dont want non-repetitive DNA in telomeres
because?
12 CSI Lab on this coming up- Microsatellites
more repeats but really short!
- Are only 1-10 nucleotides long and are repeated
only 10-100 times in the genome - Used in DNA fingerprinting (forensics)
13- What, more junk?
- (2) About 25-40 of most mammalian genomes
consists of interspersed repetitive DNA. - -One common family of interspersed repetitive
sequences, Alu elements, is transcribed into RNA
molecules with unknown roles in the cell. - -Alu sequences may help alternate RNA splicing
- -Transposons are interspersed repetitive DNA
Table 19.1 bottom
14Out of 25,000 genes what gets expressed depends
upon
- Type of cell Not all genes are expressed in all
cells (epigenetics controls it) - Development period During embryonic development
certain genes may be expressed that are not
expressed in adults (and viceversa)
15Gene families - collection of genes that may be
identical/nonidentical
16Gene families have evolved by duplication of
ancestral genes
- Most genes are present as a single copy per
haploid set of chromosomes - Multigene families exist as a collection of
identical or very similar genes (exceptions). - These likely evolved from a single ancestral
gene. - The members of multigene families may be
clustered or dispersed in the genome.
17- Identical genes are multigene families that are
clustered tandemly.
18- Evolution - first duplicate a gene and then
mutate the copy result original copy is still
there, mutated gene - could make a new protein
new function (natural selection acts on it) - Nonidentical genes have diverged since their
initial duplication event.
Pseudogenes- DNA segments that have sequences
similar to real genes but that do not yield
functional proteins - remnants of evolution or?
19Did you know your genome changes continually in
your lifetime?
- 1) Rare mutations (between 1/106 and 1/105
nucleotides ) - 2) Gene amplification selective DNA replication
of some genes to increase protein expression (ex.
after chemotherapy) - 3) Transposons/
- Retrotransposons-
- (Jumping genes)
- 50 - Corn
- 10 Human
- (Not inherited)
- 4)Gene rearrangement
Transposon moved into the purple color gene
destroying its activity
20- Altering genomes during your lifetime? continued
- Rare mutations
- Gene amplification - temporary increase
(selective loss also possible) in number of gene
copies - Transposons and retrotransposons
- Gene rearrangement in Immunoglobin genes
Fig. 19.5
21B lymphocytes (WBC) produce immunoglobins, or
antibodies, that specifically recognize and
combat viruses, bacteria, and other invaders.
- Millions of types of Antibodies can be produced
depending on what the infectious agent is - how? - Immunoglobins have constant and variable region
- 100s of gene segments code for the variable
region of the antibody. - DNA segments are put together to create an
endless combination of constant and variable
regions - gene rearrangement occurs in your
lifetime!
22TRANSLATION
TRANSCRIPTION
Promotor
RNA Polymerase makes premRNA using the elves -
transcription factors (proteins)
Many protein factors are involved in
translation as well
23 How is gene expression controlled?
- That is if/what protein is made? How can you
control this?
- Levels of control goals..
- 1) Changing DNA physically gt mRNA making
affected - 2) Changing access to DNA Promotor
- 3) If mRNA is made How long mRNA hangs around
change which protein is made from one mRNA -
(splicing) dont use the mRNA - 4) Change/destroy the protein after its made
24 How is gene expression controlled in you?
(IMPORTANT)
- When is the gene active (on or off)? That is what
protein is made? How can you control this?
- Gene expression control which genes are on
- Levels of control
- 1) chromatin (DNA) packing and chromatin
modification - change access sites on DNA for RNA
Polymerase so that its binding decreases/increases
(epigenetics - layer of control above the genome
- NOVA Video) - 2) Transcription - when DNA makes mRNA
- 3) Post-transcriptional - RNA processing,
translation - 4) Post-translational - various alterations to
the protein product.
25Fig. 19.7
26- 1a) Level of packing is one way that gene
expression is regulated. - Densely packed areas are inactivated.
(Heterochromatin) - Loosely packed areas are being actively
transcribed. (Euchromatin) -
- during mitosis
- during Interphase
27Chromatin structure is based on successive levels
of DNA packing
INTERPHASE
- Interphase - chromatin fibers highly extended
- Mitosis - chromatin coils and condenses to form
short, thick chromosomes.
MITOSIS
28- Histone proteins are responsible for the first
level of DNA packaging. - Their positively charged amino acids bind tightly
to negatively charged DNA.
Which stage do you see beads on a string?
(Interphase) Are genes active? - Yes transcribed
into mRNA!
Beads on a string a nucleosome, in which DNA
winds around a core of histone proteins
29- Next level of packing - 30 nm solenoid fiber
nucleosome fiber - Has (DNA HISTONES) with 6 nucleosomes per turn
Which stage do you see 30 nm fiber?
(Mitosis) Are genes active? - Yes transcribed
into mRNA!
30- The 30 nm fiber forms looped domains attached to
a scaffold of nonhistone proteins.
Which stage do you see looped domains?
(Mitosis) Are genes active? -No
31(No Transcript)
321b) Chromatin modifications (epigenetics)
- Chemical modifications of DNA bases
- A) DNA methylation is the attachment by specific
enzymes of methyl groups (-CH3) Inactive DNA is
highly methylated compared to DNA that is
actively transcribed. - Genomic imprinting is related to DNA methylation
33DNA Methylation - add a methyl group to make DNA
less accessibleto RNA Polymerase
341b) Chromatin modifications
- B) Histone acetylation (addition of an acetyl
group -COCH3) and deacetylation - Acetylated histones grip DNA less tightly ?
- More access to RNA Polymerase! SO,.
35Epigenetics - DNA methylation and histone
acetylation may be responsible for a lot of
traits that are not just related to whether you
have the gene/not. Example If your gene is
methylated you may never express the trait!
362) Control of Transcription very important - to
make or not make mRNA
Control elements - noncoding DNA segments that
regulate transcription by binding transcription
factors that are needed for RNA Polymerase
binding. (TATA Box -Promotor, Activators in
bacteria - Enhancers in Eukaryotes, Repressors
in bacteria - Silencers in Eukaryotes)
37- How can a DNA control element 100s of basepairs
upstream of a gene regulate the access to RNA
Polymerase? - Bending of DNA enables transcription factors,
activators (like steroid hormones), bound to
enhancers to contact the complex at the promoter.
Mostly positive gene regulation in eukaryotes!
Fig. 19.9
38- The hundreds of eukaryotic transcription factors
follow only a few basic structural principles. - Each protein generally has a DNA-binding domain
that binds to DNA and a protein-binding domain
that recognizes other transcription factors.
Fig. 19.10
393) Post-transcriptional mechanisms - so mRNA is
made, what next?
- A) RNA processing alternative splicing -
controls which protein is made from one mRNA -
mix-n-match introns/exons
403) Post-transcriptional mechanisms
- B) Life span of a mRNA molecule
- Prokaryotic mRNA molecules degraded by enzymes
after only a few minutes. - Eukaryotic mRNAs endure typically for hours or
even days or weeks.
G
AAAAA
L
T
5 Cap Leader Trailer Poly A tail
413) Post-transcriptional mechanisms
- C) Translation - can be blocked by regulatory
proteins that bind to 5 leader region of mRNA. - (prevents attachment of mRNA to ribosomes)
- Protein factors required to initiate translation
simultaneous control of translation of all the
mRNA in a cell.
G
AAAAA
L
T
5 Cap Leader Trailer Poly A tail
424) Post-translational mechanisms
- Processing of polypeptides to yield functional
proteins. - This may include cleavage, chemical
modifications, and transport to the appropriate
destination. - Regulation may occur at any of these steps.
43- The cell limits the lifetimes of normal proteins
by selective degradation. - Proteins intended for degradation are marked by
the attachment of ubiquitin proteins. - Giant proteosomes recognize the ubiquitin and
degrade the tagged protein.
Fig. 19.12
44CANCER REVIEW- read on your own - use these
animations
45 Cancer results from genetic changes that affect
the cell cycle
- Cell cycle CONTROL events dont work
- Spontaneous mutations or environmental influences
(carcinogens) - Cancer-causing genes oncogenes (retroviruses),
proto-oncogenes (in other organisms). - What happens when proto-oncogenes/oncogenes are
turned ON? (Ras gene) - Cell will divide without stopping
46- Malignant cells often have significant changes in
chromosomes
47Fig. 19.13
48 Are there genes that prevent cancer?
- Tumor-suppressor genes -normal products inhibit
cell division, repair DNA, control adhesion
(p53). - Mutations to these tumor suppressor genes
cancer
49 Oncogene proteins and faulty tumor-suppressor
proteins
50- The p53 gene, named for its 53,000-dalton protein
product, is often called the guardian angel of
the genome. - Damage to the cells DNA acts as a signal that
leads to expression of the p53 gene. - The p53 protein is a transcription factor for
several genes. - It can activate the p21 gene, which halts the
cell cycle. - It can turn on genes involved in DNA repair.
- When DNA damage is irreparable, the p53 protein
can activate suicide genes whose protein
products cause cell death by apoptosis.
513. Multiple mutations underlie the development of
cancer
- More than one somatic mutation is generally
needed to produce the changes characteristic of a
full-fledged cancer cell. - If cancer results from an accumulation of
mutations, and if mutations occur throughout
life, then the longer we live, the more likely we
are to develop cancer.
52- Colorectal cancer, with 135,000 new cases in the
U.S. each year, illustrates a multi-step cancer
path. - The first sign is often a polyp, a small benign
growth in the colon lining with fast dividing
cells. - Through gradual accumulation of mutations that
activate oncogenes and knock out tumor-suppressor
genes, the polyp can develop into a malignant
tumor.
53Fig. 19.15
54- About a half dozen DNA changes must occur for a
cell to become fully cancerous. - These usually include the appearance of at least
one active oncogene and the mutation or loss of
several tumor-suppressor genes. - Since mutant tumor-suppressor alleles are usually
recessive, mutations must knock out both alleles.
- Most oncogenes behave as dominant alleles.
- In many malignant tumors, the gene for telomerase
is activated, removing a natural limit on the
number of times the cell can divide.
55- Viruses, especially retroviruses, play a role is
about 15 of human cancer cases worldwide. - These include some types of leukemia, liver
cancer, and cancer of the cervix. - Viruses promote cancer development by integrating
their DNA into that of infected cells. - By this process, a retrovirus may donate an
oncogene to the cell. - Alternatively, insertion of viral DNA may disrupt
a tumor-suppressor gene or convert a
proto-oncogene to an oncogene.
56- The fact that multiple genetic changes are
required to produce a cancer cell helps explain
the predispositions to cancer that run in some
families. - An individual inheriting an oncogene or a mutant
allele of a tumor-suppressor gene will be one
step closer to accumulating the necessary
mutations for cancer to develop.
57- Geneticists are devoting much effort to finding
inherited cancer alleles so that predisposition
to certain cancers can be detected early in life. - About 15 of colorectal cancers involve inherited
mutations, especially to DNA repair genes or to
the tumor-suppressor gene APC. - Normal functions of the APC gene include
regulation of cell migration and adhesion. - Between 5-10 of breast cancer cases, the 2nd
most common U.S. cancer, show an inherited
predisposition. - Mutations to one of two tumor-suppressor genes,
BRCA1 and BRCA2, increases the risk of breast and
ovarian cancer.