Transcript Eukaryotic Genomes - Building Directory

Eukaryotic Genomes
Chromatin Structure
If stretched out, each chromosome
would be approximately 4cm long
 Chromatin is made up of DNA and the
proteins that condense it
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If DNA did not associate with proteins
in this way, what would be the
problem?
Chromatin Structure
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Nucleosomes
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The DNA double helix wraps around proteins called
histones
This gives the appearance of “beads on a string”
The “beads” (nucleosomes) are joined by “string”
(linker DNA)
Chromatin Structure
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The nucleosomes
interact with one
another to coil and fold
multiple times in a
specific conformation
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30-nm fiber
Looped domains
Mitotic chromosomes
(most tightly
condensed)
The Regulation of Gene
Expression
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All cells in an organism contain an identical genome (set
of genes)
However, the genes expressed in the cells of each type
are unique
Most of the DNA in eukaryotic genomes are noncoding –
unsure of its purpose
 25,000 genes in humans
 Only about 1.5% codes for protein
The expression of specific genes is most commonly
regulated at transcription, often in response to external
signals
 Genes are turned on and off
 Transcription is the most common regulatory point in the
pathway of gene expression, but it can happen at a
number of places as well
Cancer
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Mutations that alter genes that regulate cell
growth and division can lead to cancer
These mutations can be random and
spontaneous
 More commonly, however, these mutations
are caused by environmental influences
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• Examples?
Oncogenes and Proto-Oncogenes
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Oncogenes: cancer-causing genes
Proto-oncogenes: genes that stimulate normal cell
growth and division
Proto-oncogenes (normal) can become
oncogenes (abnormal; cancer-causing) in a
number of ways
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Translocation of gene
Gene amplification – more copies of gene
Point mutations
All of these possibilities cause more growthstimulating protein to be produced
Oncogenes and Proto-Oncogenes
Tumor-Suppressor Genes
The products of tumor-suppressor
genes inhibit cell division and help
prevent uncontrolled cell growth
 If a mutation occurs that affects
tumor-suppressor genes, cancer may
result
 p53 is a tumor-suppressor gene that
activates other genes to repair DNA
damage and inhibit further cell division
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The Multistep Model of
Cancer Development
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Usually, more than one mutation is required
to produce a cancerous cell
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Since cancer results from an accumulation
of mutations, the longer we live the more
likely we are to develop cancer
In most cases of cancer, at least one active
oncogene appears and at least one tumorsuppressor gene is mutated or lost
Inherited Predisposition to Cancer
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Certain types of cancer can run in families
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Since cancer is caused by the
accumulation of multiple genetic changes,
an individual who inherits an oncogene or
mutant tumor-suppressor gene is “that
much closer” to accumulating the required
number of mutations to develop cancer
Transposons
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Transposons (“jumping
genes”) are sequences of
DNA that can move around
to different positions within
a single cell
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Can cause mutations and
change the amount of DNA
in a cell
Discovered by Barbara
McClintock in 1933 in
maize (corn)
Transposons
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Transposons are mutagens
and damage the DNA of the
host cell in a number of ways:
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A transposon that inserts itself
in the middle of a functional
gene will likely damage or
disable that gene
If a transposon leaves a gene,
the gap will probably not be
repaired correctly