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Chapter 11
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Gene
Expression
http://www.youtube.com/watch?v=oBwtxdI1zvk&feature=related
What is gene expression?
• DNA
RNA
Proteins
• Turning “on” and “off” genes
• Don’t need specific proteins
all the time
• Make them when you need
them
Gene Expression in
Prokaryotes
• E. coli (bacteria that live in
intestines of mammals)
• Discovered how genes control the
metabolism of the sugar lactose
• Lactose: disaccharide made of
glucose and galactose
• Milk sugar
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When there is/is not lactose
LACTOSE PRESENT: It induces E. coli
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metabolize
lactose
LACTOSE ABSENT: three enzymes will
not be made. Lactose will not be
broken down.
Operon: series of genes that code
for specific products and
the regulatory elements
that control these genes
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Lac operon:
segment of DNA that
codes for the enzymes
that regulate lactose
metabolism
DNA of E.coli
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Regulator gene: codes for repressor gene
Promoter: DNA segment that is recognized by the
enzyme RNA pol
Operator: DNA segment that serves as a “switch”
controlling the access of RNA pol to the promoter
Structural genes: code for 3 enzymes that break down
lactose
Operon “turned off”
• Repressor protein attaches to the operator
physically blocking RNA pol from attaching
RNA pol
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Operon “turned on”
• Lactose present (acts as inducer
starts gene expression)
• Binds to the repressor protein
• Repressor changes shapes and
detaches from operator
• RNA pol is not blocked anymore
• All three enzymes can be produced
Operator “turned on”
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lactose
Why is this
good?
• E. coli is able to turn off and on genes
when lactose is present/absent
• Bacteria saves resources and
produce only those proteins that are
needed
Let’s watch it again
• http://www.youtube.com/watch?v=oBwtxdI1zvk&featu
re=related
Eukaryotes
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• How is DNA different
than Prokaryotes?
• “junk DNA”
• ~98% Non-coding
• Operons not found very
often
• Gene expression occurs
at the level of the
individual chromosome
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• Introns: “non-coding sections”
– are transcribed but not translated
~ 98% of genome
• Exons: “coding sections”
– are transcribed and translated
~2% of genome (23,688 human genes)
Modification of RNA
• Transcription: both introns and exons are transcribed:
pre-mRNA
• Introns are removed and exons are spliced (joined) together
• Result: mRNA only with exons (coding regions)
• What spliced the DNA?
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snRNPs
• Small nuclear ribonucleoproteins
• Composed of a small protein molecule and RNA
Pronounced “snurps”
60-300 nucleotides
Also called “spliceosomes”
responsible for pre-mRNA splicing
Beginning and ends of introns are recognized
and removed
• At least 4 different kinds of snRNPs
•
•
•
•
•
• Main ones (U1, U2, U4&U6, U5)
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Alternative splicing
• Shuffle exons
• Produce alternative
ribonucleotide
arrangements
• Produces different
proteins (isoform
proteins)
• Synthesis greater
variation of proteins
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What about the introns?
• Perhaps not just “junk”
• Regulation functions and Structural purposes
• "the cell puts a huge amount of its energy into the creation of
these introns, then discards them ... Nature would not go to
all that trouble without a reason."
– C.C. Kopezynski and M. A. T. Muskavitch
• "a complex mix of different DNA, much of which are vital to
the life of the cell."
– Nowak
• At least a dozen studies have found evidence that introns are
either directly or indirectly involved in cancer causation.
• “..at least some introns, and possibly other noncoding DNA,
may be involved in DNA packaging in eukaryotes”
– Marculis and Sagan
Control at Transcription
• Transcription Factors: regulatory
proteins
– Help in the placement of RNA pol at the
promoter
• Enhancers: (located far away..upstream
or downstream) stimulates transcription
– Pg 222
Cell differentiation: development of
cells that have specialized functions
Homeotic Genes
• Guide the
emergence of shape
and form
• Drosophilia (fruit fly)
• Homeobox: Specific
180nb DNA
sequence within a
homeotic gene
Mutation in Homeobox
Cancer
Four changes
1. Immortalization: indefinite growth and
replication
2. Transformation: becomes independent of
factors needed for cell growth
3. Angiogenesis: recruit vascular supply
4. Metastasis: cells dissociate from origin and
begin invading normal tissue
Angiogenesis
Pathways of mutation
Need to accumulate mutations in 6 pathways
Cells die after about 60 division
• Telomeres (caps) on end of chromosome
– Get smaller and smaller
– Suicide (apoptosis)
•
Tumor cells-telomerase-puts caps back on
(live forever)
Cytochrome c in mitochondria
• Involved in cell suicide (apoptosis)
Oncogenes: mutation of proto-oncogene
(regulate cell growth and division)
• Gene that causes uncontrolled cell
proliferation
• May lead to over expression of
proteins
• Over 100 oncogenes identified
Tumor-suppressor genes
• Act as “brakes”
• ~30 identified
• Slow cell division, repair DNA mistakes,
tell cells when to die (apoptosis)
• Can lead to cancer when don’t function
properly
• Abnormalities can be inherited as well
as acquired (oncogenes:mutations)
Carcinogens
• Substance that can
induce or promote
cancer
• Most are mutagens
• Chemicals in
tobacco smoke,
asbestos, radiation,
UV
Viruses can also
cause cancer
HPV
Types of Cancer
Carcinomas: grow in the skin and
tissues that line organs
Sarcomas: grow in bone and
muscle tissue
Lymphomas: grow in the
lymphatic system
Leukemia: uncontrolled
production of white blood cells