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CHAPTER 19 THE ORGANIZATION AND CONTROL OF EUKARYOTIC GENOMES = Larger than prokaryotes Not all 25,000 genes are active in all cells – PowerPoint PPT presentation

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Title: Nerve activates contraction


1
CHAPTER 19THE ORGANIZATION AND CONTROL OF
EUKARYOTIC GENOMES
  • gt Larger than prokaryotes
  • Not all 25,000 genes are active in all cells

2
Junk 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)
3
Noncoding 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.

4
REPPPPETITIVE 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)
5
REPPPPETITIVE 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.
  • CAG
  • Repeat

7
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9
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10
You 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
14
Out 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)

15
Gene families - collection of genes that may be
identical/nonidentical
16
Gene 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?
19
Did 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
21
B 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!

22
TRANSLATION
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.

25
Fig. 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
27
Chromatin 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
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32
1b) 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

33
DNA Methylation - add a methyl group to make DNA
less accessibleto RNA Polymerase
34
1b) 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,.

35
Epigenetics - 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!
36
2) 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
39
3) 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

40
3) 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
41
3) 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
42
4) 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
44
CANCER 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

47
Fig. 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.

51
3. 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.

53
Fig. 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.
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