chapter 11 gene expression
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Chapter 11Gene 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 QuickTime™ and a decompressor
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When there is/is not lactose
LACTOSE PRESENT: It induces E. coli to produce three enzymes which will metabolize lactose
LACTOSE ABSENT: three enzymes will not be made. Lactose will not be broken down.
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Operon: series of genes that code for specific products and the regulatory elements that control these genes
Lac operon: segment of DNA that
codes for the enzymes that regulate lactose metabolism
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DNA of E.coli
Regulator gene: codes for repressor genePromoter: DNA segment that is recognized by the enzyme
RNA polOperator: DNA segment that serves as a “switch” controlling
the access of RNA pol to the promoterStructural genes: code for 3 enzymes that break down lactose
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Operon “turned off”• Repressor protein attaches to the operator
physically blocking RNA pol from attaching
RNA pol
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
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• 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&feature=related
Eukaryotes• 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)
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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 supply4. Metastasis: cells dissociate from origin and
begin invading normal tissue
Angiogenesis
Pathways of mutationNeed to accumulate mutations in 6 pathwaysCells 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