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Eukaryotic Genomes

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Eukaryotic Genomes Organization, Regulation & Evolution Chromatin/Chromosome Structure A.) Chromatin: loose, uncoiled form of DNA combined with protein. – PowerPoint PPT presentation

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Title: Eukaryotic Genomes


1
Eukaryotic Genomes
  • Organization, Regulation Evolution

2
Chromatin/Chromosome Structure
  • A.) Chromatin loose, uncoiled form of DNA
    combined with protein. Coils to form the 46
    distinct chromosomes.
  • 1.) Each condensed chromosome is made of a
    single, linear DNA molecule that would be over 4
    cm long if stretched out! How does it all fit??
  • a.) There is an elaborate system of DNA
    coiling packing that fits all the DNA into a
    cells nucleus.

3
  • 2.) First, DNA is coiled around proteins called
    histones.
  • a.) This forms structures called nucleosomes.
    Under the electron microscope, these look like
    beads on a string.

4
  • 3.) The nucleosomes DNA between them fold
    back on each other, looping and coiling eve
    further. During mitosis, when the chromosomes are
    very condensed, this is even more apparent.

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Gene Regulation
  • Gene regulation is extremely important!
  • - In prokaryotes, genes are regulated (turned
    on or off) through the action of
    repressors/inducers on operons.
  • - Regulation of eukaryotic genes is more
    complex.
  • - Remember all your cells have your entire
    genome. Cells function differently because they
    express (turn on/off, transcribe/translate)
    different genes.

8
  • So the differences between cell types is not due
    to different genes being present, but to
    differential gene expression.
  • There are many stages of gene expression from the
    level of DNA to the final protein product and
    gene expression can be regulated at ANY of these
    in eukaryotic cells.

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  • A.) Regulation of Chromatin Structure
  • 1.) DNA located in areas where chromosomes are
    VERY tightly packed is not expressed.
  • 2.) Histone Modification
  • a.) Histone acetylation attachment of
    acetyl groups (-COCH3). Prevents histones from
    binding with one another looser structure
    easier for transcription.
  • b.) Histone methylation (-CH3) opposite
    affect chromsome condensation.

11
  • 3.) DNA methylation attachment of methyl
    groups inactive (not expressed) DNA.
  • a.) Once methylated, genes usually stay that
    way. Daughter strands are methylated after
    replication.
  • So these modifications of DNA (that do not
    involve the DNA sequence itself) can be passed on
    to future generations of cells. This type of
    inheritance (of traits not involving the
    nucleotide sequence) is called epigenetic
    inheritance.

12
  • B.) Regulation of Transcription Initiation
  • 1.) Review of eukaryotic gene organization
  • a.) There is a promoter sequence prior to the
    start of the gene. The gene itself consists of
    introns exons. There is a termination sequence
    after the gene.
  • b.) Additionally, there are sequences called
    control elements that bind proteins associated
    with transcriptions.
  • c.) Remember, for transcription to start, many
    transcription factors must be bound to the
    promoter region along with RNA polymerase to
    form the transcription initiation complex.

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  • 2.) Enhancers specific transcription factors
  • a.) Sequences called control elements (which
    can be close to the promoter or many nucleotides
    before it) have specific transcription factors
    (activators repressors) that bind to them.
  • b.) The binding of these transcription factors
    (activators) bends the DNA and helps
    assemble/position the initiation complex.

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  • c.) Repressors can block the binding of
    activator transcription factors and prevent
    formation of initiation complex.
  • d.) Activators repressors can even add/take
    away acetyl groups on histones to promote/silence
    transcription.
  • e.) Different genes have different combos of
    control elements and the presence/absences of
    activators in cells helps determine which genes
    are being expressed.

17
  • 3.) Transcription of related genes in
    eukaryotes (remember no operons)
  • a.) Coordinated transcription of related genes
    usually occurs in response to an external signal
    (like a hormone).
  • b.) This signal will bind to a protein form
    an activator that will be able to bind to any
    gene stimulated by that particular hormone.
  • c.) So genes with the same control elements
    are activated by the same chemical signals.

18
  • C.) Post-transcriptional regulation
  • 1.) RNA processing alternative RNA splicing
  • 2.) mRNA degradation certain nucleotide
    sequences present on mRNA molecules can cause it
    to be broken down more quickly.

19
  • 3.) microRNAs (miRNAs) small RNA molecules
    associated with proteins that can bind to
    complementary strands of mRNA to block
    translation or to break it down.
  • 4.) Translation initiation can be blocked by
    regulatory proteins.

20
  • 5.) Post-translation regulation many
    proteins must undergo modification addition of
    different molecules to be functional. Regulation
    can occur at any step.
  • 6.) Protein degradation proteins are marked
    for destruction by the attachment of certain
    molecules that are recognized by other molecules
    that will then break down the protein.

21
A Closer Look at Cancer
  • Remember, cancer arises from mutations in genes
    that code for growth factors, their receptors or
    for molecules in signaling pathways involved in
    cell cycle regulation.
  • A.) Proto-oncogenes the name given to genes
    that stimulate normal cell growth division.
  • 1.) If any of these genes mutates becomes
    cancer causing, it is then referred to as an
    oncogene.

22
  • B.) Genetic changes that convert
    proto-oncogenes to oncogenes
  • 1.) Movement of DNA within the genome (can
    place a more active promoter near a
    proto-oncogene increasing its activity)
  • 2.) Amplification of proto-oncogene (an
    increase in copies of the gene
  • 3.) Point mutation in control elements of gene
    or in gene itself (increase in expression or
    change in protein product that is resistant to
    degradation)

23
  • C.) Tumor-suppressor genes encode proteins
    that inhibit cell division help prevent
    uncontrolled growth.
  • 1.) Mutations can decrease the activity of
    these genes contributing to onset of cancer.
  • Read about the ras p53 genes!

24
  • D.) More than one mutation in a cell is usually
    needed for a cell to turn cancerous.

25
Noncoding DNA Sequences in Eukaryotic Genomes
  • Only 1.5 of our genome codes for proteins RNAs
    what the heck is the rest of it for????

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  • A.) Transposable elements segments of DNA that
    can move locations within the genome. (make up
    25-50 of most mammalian genomes)
  • 1.) Transposons move within in a genome by
    means of a DNA intermediate
  • 2.) Retrotransposons move by means of an RNA
    intermediate

28
  • B.) Repetitive DNA about 15 of genome
  • 1.) Much of this is located at telomeres and
    centromeres so perhaps it plays a structural role
    in chromosomes.

29
  • C.) Multigene families collections of
    identical or very similar genes (most likely
    arising from gene duplication through time)
  • 1.) Example family of genes that codes for
    rRNA molecules. Many copies of this gene allows
    cells to make all the ribosomes needed for
    translation (protein synthesis).

30
  • 2.) Example hemoglobin genes exist in various
    similar forms. Different forms are expressed at
    different times during human development. Fetal
    hemoglobin has a higher oxygen affinity than
    adult hemoglobin to facilitate obtaining oxygen
    from mother!
  • Read about the evolution of the eukaryotic genome
    through duplication of genes, rearrangements,
    mutations and the action of transposons (pages
    378-381).
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