Chapter18: Molecular Genetics of the Eukaryotes

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Chapter18 Molecular Genetics of the Eukaryotes

• By
• Jonathan Kroopf

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Eukaryotic chromosome and its structure

• The DNA of each eukaryotic chromosome is believed
  to be in the form of a single molecule.
• Double strand DNA is always a helix.

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Z-DNA B-DNA
Right handed B-DNA (type discovered by Watson and
Crick)
Left handed Z-DNA
Changes in configuration may change the binding
of proteins and thus gene expression
http//cmgm.stanford.edu/
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Eukaryotic chromosome and its structure

• In the nucleus of the eukaryotic cell, the DNA is
  always found combined with proteins.
• Chromatin is more then half protein, and the most
  abundant proteins, by weight,
• belong to a class of small polypeptides known as
  histones.
• There are five types of histones, h1, h2a, h2b,
  h3 and h4.
• http//www.virtuallaboratory.net/Biofundamentals/l
  ectureNotes/Topic3-9_NucleicAcid.htm

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http//departments.oxy.edu/biology/bio130/lectures
_2000/11-27-00.htm
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Eukaryotic chromosome and its structure

• The fundamental packing unit of chromatin is the
  nucleosome, which is composed of a core molecule
  each of histones h1, h2a, h2b, h3 and h4.

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Regulation of gene expression in Eukaryotes

• Since each type of cell produces only it
  characteristic proteins  and not the proteins
  characteristics of other cell types it  becomes
  apparent that differentiation of the cells of
  multicellular organisms depends on the
  inactivation of certain groups of genes and the
  activation of others.
• Transcription is regulated by proteins that bind
  to specific sites on the DNA molecule.

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Condensation of the chromosome and gene expression

• Staining reveals two types of chromatin
• 1. Euchromatin, the more open chromatin which
  stains weakly
• Heterochromatin, the more condensed chromatin,
  which stains strongly.

http//www.nenno.it/publications/mnphdthesis/diss1
9.htm
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Condensation of the chromosome and gene expression

• As a cell differentiates during embryonic
  development, the proportion of heterochromatin to
  euchochromatin increases as the cell becomes more
  specialized.
• The looping out of DNA occurs before RNA
  synthesis is initiated.

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Methylation and gene expression

• Methyl is added to nucleotides of cytosine
• In birds and mammals 50-70 of cytosine in C-G
  and G-C sequences are methylated
• Is found primarly on inactive Z-DNA

http//www.hopkins-gi.org/pages/latin/templates/in
dex.cfm?pgresearch2pageID15
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Regulation by Specific binding proteins

• Regulation on the transcriptional level in
  eukaryotes is mediated mainly by DNA-binding
  proteins that exhibit a controlling function on
  the process of DNA transcription.

http//www.amiravis.com/mol/gallery/pic9.html
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The Eukaryotic Genome
The amount of DNA of every cell is the same for
every species. Eukaryotes use less then 10 of
all DNA codes for proteins in humans it may be
less than 1 Almost half of the DNA of the
eukaryotic cell consists of nucleotides that are
repeated hundreds of times, unlike prokaryotes.
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Introns
Noncoding interruptions within the genes are know
as intervening sequences, or Introns. The
sequences that are expressed are called
exons. Introns Promote recombination which helps
in crossing over phase of meiosis. Different
exons code for different structural and fuctional
segments.
http//www.mun.ca/biology/scarr/Exon_Intron_struct
ure.htm
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Classes on DNARepeats and Nonrepeats

• Discovered in hybridizations experiments
• Simple-sequence DNA
• Reassociates rapidly indicating multiple copies
• Intermediate-repeat DNA
• Reassociates more slowly
• Single-Copy DNA
• Only one or a few copies of the DNA are present

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Simple-Sequence DNA

• Easy to analyze due to short sequence
• Are typically 5 to 10 base pairs long, although a
  few are as long as 200 to 300 base pairs
• Vital to chromosome structure

http//www.dna-res.kazusa.or.jp/3/4/02/HTMLA/img38
.gif
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Intermediate-Repeat DNA

• Slower than simple sequences
• 150 to 300 nucleotides
• Scattered throughout the genome
• Many closlely related but not exact-called
  families
• Most have no known functions
• Exception genes coding for histones and
  ribosomal RNA

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Single Copy DNA

• 50 to 70 of the genome
• Is mainly made up of sequences that are not
  repeated.
• With exception of histones all protein coding
  genes are single copy DNA
• But as little as 1 are translated in proteins

http//www.mun.ca/biology/scarr/4241F2_DNA.html
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Gene Families

• The best studied of the gene families is the
  globin family.
• The shows its evolution.

http//homepages.strath.ac.uk/globinfamily1.jpg
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Transcription and processing of mRNA in
Eukaryotes.

• Transcription in eukaryotes is the same in
  principal as in prokaryotes. It begins with the
  attachment of a special enzyme, an RNA
  polymerase, to a particular nucleotide sequence,
  the promoter, on one strand of the DNA double
  helix.
• After transcription is completed in the nucleus,
  the mRNA transcripts are extensively modified
  before they are transported to the cytoplasm-the
  site of translation.

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Transcription continued

• Prokaryote
• Single RNA polymerase catalyzes the biosynthesis
  of the three types of RNA mRNA, tRNA, rRNA

• Eukaryote
• Genes are not grouped in operons, each structural
  gene is transcriped seprately
• 3 types of RNA polymerase

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mRNA Modification and Editing

• Transcription and translation are seperated by
  both time and space (not like prokaryote)
• 7- methyguanine cap added to forming mRNA on 5
  end, needed to bind mRNA to ribosome

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Antibody-coding genes

• Antibodies are complex globular proteins produced
  in large quantities by specialized white blood
  cells in response to the presence of foreign
  molecules.
• A substance that evokes the production of
  antibodies is known as an antigen.

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Viruses

• Consist essentially of nucleic acid enclosed in a
  protein capsid.
• When integrated viruses are known as proviruses.

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Eukaryotic Transposons

• Eukaryotic transposons resemble their bacterial
  counterparts in structure.
• They can cause mutations when they become
  inserted into structural genes or promoter
  regions.

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Cancer
http//www.cancerhelp.org.uk/cancer_images/invade.
gif
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Viruses and Cancer

• Viruses, like mutagen can bring about changes in
  the cells genetic makeup.
• Cancer causing viruses are viruses that introduce
  information to the host cell chromosomes

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Transfers of genes between Eukaryotic cells

• The future hope is that genetic affects can be
  corrected by substituting bad genes with good
  genes.
• Foreign genes will undergo recombination in
  eukaryotic cells growing in a test tube.
• John w. Gordon and Frank Ruddle were the first
  to insert a DNA sequence into the fertilized eggs
  of mice.
• Allan Spradling and Gerald Rubin used naturally
  occurring transposons of the Drosophilia to ferry
  genes into embryonic fruit flies.