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The Nature of Transposons Chapter 11 pp 300-315
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Outline Nature of Transposons Transposons
Prokaryotic Eukaryotic: Dr. McClintock’s research Retrotransposons vs Retroviruses
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Transposons Are mobile DNA sometimes referred to as “jumping genes”.
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Why are transposons in our genome?
Cellular function hypothesis Antibody diversity of VDJ Genetic variation hypothesis Self-DNA hypothesis
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Common features associated with transposons
1. Direct repeats Common Features Are: 2. Terminal Inverted repeats
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Mechanisms of Transposition
Movement through DNA intermediates Movement through RNA intermediates
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DNA Transposition Movement through DNA intermediates Replicative
Cut and Paste Copy and Paste Movement through DNA intermediates Replicative Non-Replicative
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Non-Replicative Movement by Transposition
Requires transposase 1) Transposase cuts transposon out of donor DNA (blunt cut) 2) Transposase makes a staggered cut at the target sequence 3) Transposase ligates transposon into the target 4) Gaps are filled in with DNA pol I and ligase
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Direct repeats are generated
Staggered cut Direct repeats are generated
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Direct repeats are generated
Staggered cut Direct repeats are generated
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Examples of: Transposable Elements in Bacteria
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1. Simple Bacterial Transposon
INSERTION SEQUENCE
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2. COMPOSITE TRANSPOSON IS + any DNA segment
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Physiology or Medicine
Dr. Barbara McClintock Nobel Prize, 1983 Physiology or Medicine
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“I don’t understand a word that she said, but if she says it is so, it must be so!” Alfred Sturtevant
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The Ds element often results in chromosomal breakage
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Drosophilia melanogaster & DNA transposition “The P Element”
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The P element Codes for both
Transposase Repressor of transposition
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Female P- and male P+ Female P+ and male P- Offspring sterile Offspring normal Non-hybrid dysgenesis Hybrid dysgenesis Why the difference?
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Remember the P element Codes for
A Transposase AND A Repressor of transposition
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The P element took a ride on a
Science Sep 6;253(5024): Possible horizontal transfer of Drosophila genes by the mite Proctolaelaps regalis. Houck MA, Clark JB, Peterson KR, Kidwell MG. D. willistoni The P element took a ride on a ~50 yrs ago That moved it onto Mite D. melanogaster
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Retrotransposons mRNA DNA
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Examples of retrotransposons elements
Yeast Ty Copia Alu Drosophila Humans
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Note: retrotransposons are not found in prokaryotes
General Mechanism Of Retrotransposons Note: retrotransposons are not found in prokaryotes
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Types of Retrotransposons
Humans Alu Non-Viral Yeast Ty Copia Viral Drosophila
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Non-viral Retrotransposons
Humans Non-Viral LINES SINES Example: Line 1 and Line 2 Alu
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ALU 300 bp Endonuclease cutting site: site5' AG/CT 3‘ Retrotransposon
1 million in genome Linked to variety of disorders
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Alu has inserted in NF-1 gene
Neurofibromatosis: autosomal dominant Growth of nodules mainly affecting nerves in the skin
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Viral retrotransposons look a little like retroviruses—but are NOT the same !
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Now we must compare a Viral RNA with a Viral Retrotransposon
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VIRAL RNA
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Now a viral retrotransposon
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Compare to the retrovirus
Here’s the Copia element of Drosophila Similar gag and pol sequences Compare to the retrovirus
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Here’s the Ty element, again notice similarities to retroviruses
Delta sequences function like LTR’s in viruses
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Summary Table Viral and non-viral Ty and Copia viral retrotransposons
Alu non viral retrotransposons
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A topic of scientific discussion is what is a “prion”?
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Blunt cut from donor
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HUMAN IMMUNODEFICIENCY VIRUS Human Helper T Lymphocyte
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