Transcript Ch 11 Transposable Elements

The Nature of Transposons
Chapter 11
pp 300-315
Outline
• Nature of Transposons
• Transposons
– Prokaryotic
– Eukaryotic: Dr. McClintock’s research
• Retrotransposons vs Retroviruses
Transposons
• Are mobile DNA sometimes referred to as
“jumping genes”.
Why are transposons in our genome?
• Cellular function hypothesis
– Antibody diversity of VDJ
• Genetic variation hypothesis
• Self-DNA hypothesis
Common features associated with
transposons
Common
Features
Are:
1. Direct
repeats
2. Terminal
Inverted
repeats
Mechanisms of Transposition
• Movement through
DNA intermediates
• Movement through
RNA intermediates
DNA Transposition
Replicative
Cut and Paste
Copy and Paste
• Movement through
DNA intermediates
Non-Replicative
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
Staggered cut
Direct repeats are generated
Staggered cut
Direct repeats are generated
Examples of:
Transposable Elements in Bacteria
1. Simple Bacterial Transposon
INSERTION SEQUENCE
2. COMPOSITE TRANSPOSON
IS + any DNA segment
Dr. Barbara McClintock
1902-1992
Nobel Prize, 1983
Physiology or Medicine
“I don’t understand a
word that she said, but if
she says it is so, it must
be so!”
Alfred Sturtevant
The Ds element often results in chromosomal breakage
Drosophilia melanogaster
&
DNA transposition
“The P Element”
The P element Codes for both
• Transposase
• Repressor of transposition
Female P- and male P+
Offspring normal
Offspring sterile
Hybrid dysgenesis
Female P+ and male P-
Why the difference?
Non-hybrid dysgenesis
Remember the P element Codes for
• A Transposase
• AND
• A Repressor of transposition
D. willistoni
Science. 1991 Sep 6;253(5024):1125-8
Possible horizontal transfer of Drosophila genes by the
mite Proctolaelaps regalis.
Houck MA, Clark JB, Peterson KR, Kidwell MG.
~50 yrs ago
That moved it onto
Mite
D. melanogaster
Retrotransposons
DNA
mRNA
Examples of retrotransposons elements
• Ty
Yeast
• Copia
• Alu
Drosophila
Humans
General Mechanism
Of Retrotransposons
Note: retrotransposons are not found in prokaryotes
Types of Retrotransposons
• Alu
• Ty
Humans
Non-Viral
Yeast
Viral
• Copia
Drosophila
Example:
Non-viral Retrotransposons
Humans
Non-Viral
LINES
SINES
Line 1 and Line 2
Alu
ALU
• 300 bp
• Endonuclease cutting site: site5' AG/CT 3‘
• Retrotransposon
• 1 million in genome
• Linked to variety of disorders
Alu has inserted in NF-1 gene
Neurofibromatosis: autosomal dominant
Growth of nodules mainly affecting nerves in the skin
Viral retrotransposons look a little like
retroviruses—but are NOT the same !
Now we must compare a Viral RNA
with a Viral Retrotransposon
VIRAL RNA
Now a viral retrotransposon
Here’s the Copia element of Drosophila
Similar gag and pol sequences
Compare to the retrovirus
Here’s the Ty element, again notice similarities to retroviruses
Delta sequences function like LTR’s in viruses
Summary Table
Viral and non-viral
Ty and Copia viral retrotransposons
Alu non viral retrotransposons
A topic of scientific discussion is
what is a “prion”?
Blunt cut from donor
HUMAN
IMMUNODEFICIENCY
VIRUS
Human Helper T Lymphocyte