630430019-Transposons-in-humavety usefulns.pdf

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1. 1
In
Transposons
Humans

2. 2
Introduction :
•Barbara McClintock first discovered transposable
elements in corn in the 1940.
•Transposable elements (TEs) are, DNA
transposons move from one genomic location to
another by a cut-and-paste mechanism.
Transposon contents in eukaryotic genomes vary
from <1% to >85%. By default.
•They are found to encode a special protein named
transposase.
•Transposons are particular to different groups of
organism.

3. Figure: 1.1 "Cut and Paste" transposable element mechanism of excision and
insertion into target site. 3

4. 4
Transposable elements
Viral
Transposon
LTR
elements
Retroviral
Drosophila-
copia
Yeast- Ty
Non- viral
transposon
Non- LTR
(UTR)
LINES
SINES
(Alu)
Bacterial
IS elements
Bacteria
Maize
AC/DS
Flow Chart: 1.1

5. 5
Graph: 1.1
Slayter, J. (2020, September 6). Retrotransposons: A balancing act at the
genome scale. Atlantic Student Research Journal. Retrieved October 21, 2022,
from https://theasrj.com/articles/effects-regulation-transposons

6. 6
Class I TEs: "Copy and Paste" Transposition
A Class I TE (=
 
retrotransposon) uses a
 
”copy and paste”
mechanism to transpose.
A retrotransposon
•contains a gene encoding
 
reverse transcriptase
•never leaves its DNA location
•is transcribed into an
 
RNA intermediate.
•The new retrotransposon inserts at another
 
target site 
in
the DNA.
•This creates a new copy of the retrotransposon, so one
resides at
othe original location
oa new location

7. 7
Figure: 1.2 Class I TEs: "Copy and Paste" Transposition

8. 8
Retrotransposons can proliferate and insert many times in a genome.
Eukaryotes can have more reverse transcriptase genes
than any other exome genes!
There are two types of retrotransposons :
1. Long Terminal Repeat (LTR) retrotransposons
flanked by two several-hundred base pair
 
direct repeats (DR)
2. Non-LTR retrotransposons
lack flanking repeats
Retrotransposons Key features :
•env 
gene is absent or nonfunctional
 
in retrotransposons.
•Retrotransposons are not infectious, and never leave their host
cell.

9. 9
Retrotransposons in Eukaryotic Genomes: LINEs and SINEs
Large genomes have tremendous numbers of transposable elements.
Some may be composed
 
mostly 
of transposable elements.This may help
explain the
 
C-value paradox.
More than half of the human genome consists of
•long interspersed elements (LINEs)
•short interspersed elements (SINEs)
•Most no longer transpose, but can still be identified by the presence of
flanking inverted repeats.
•A vast number are found only in introns.
•These are excised and never translated.
•They are
 
evolutionary relics 
rendered harmless by
otheir benign insertion location
othe host's regulatory mechanisms

10. 10
The most abundant SINE in the human genome contains a target site
for the Alu (from Arthrobacter luteus) restriction enzyme.
This SINE is named the Alu element.
•Alu elements comprise more than 10% of the human genome.
•There are more than one million copies of various Alu fragments in every
human genome.
Recall the idea of a "selfish" DNA sequence:
•It spreads by forming additional copies of itself within the genome.
•It makes no specific contribution to the reproductive success of its host.
•It may be neutral or maladaptive.
Class II Transposable elements generally fit this description

11. 11
A few human DNA TEs
can still transpose.
Some are associated with
specific diseases:
Hemophilia A 
(three
different LINE insertions
in clotting factor VIII
gene)
Hemophilia B 
(insertion
into the clotting factor IX
gene)
Neurofibromatosis 
(
Alu 
i
nsertion into the
 
NF1 
gene
Breast
Cancer 
(
Alu 
insertion into
the
 
BRCA2 
gene)
Table : 1.1

12. 12
Class II Transposons: Structure
A Class I transposon contains
•an ORF encoding transposase
•two 31-nucleotide inverted repeat (IR) sequences flanking the ORF
(one on each end)
oThe inverted repeats are the transposase binding sites.
•two eight-nucleotide direct repeat (DR) sequences flanking the entire
TE (one on each end)
oThese are not part of the transposon.
oThey remain behind after the transposon is excised for
transposition
Figure: 1.3 Structure of class 2 transposons

13. 13Figure: 1.4

14. 14
DNA Repeat Sequences
Transposition of TEs can generate short segments of
 
DNA repeats.
There are many types of repetitive DNA sequences, but the ones most
commonly associated with transposons are shown on the left.
1. Direct repeats (DR)
are two or more repeats of a specific sequence.
are found in multiple copies in the genome.
2. Inverted repeats (IR)
are mirror image repeats across from each other on opposite DNA
strands
have complementary sequences downstream on the same strand
form palindromes
may be separated from each other by intervening nucleotides
3. Mirror repeats
have a center of symmetry
identical terminal nucleotides
are sequences forming mirror images of each other

15. 15
Class II TEs: "Cut and Paste" Transposition
Class II TEs use a "cut and paste" mechanism to transpose.
•The TE encodes transposase, which catalyzes transposition.
•Transposase recognizes and binds to the transposon's 3' and 5' ends.
•Transposase then excises the TE from its DNA location. (excision)
•Cellular repair mechanisms repair the cleavage site.
oDirect repeats are joined, leaving a "footprint": evidence of the TE's
exit.
oThese remnant direct repeats serve as future target sites.
•Transposase then moves the bound TE to another DNA location (drift)
•Transposase cleaves the target site, leaving "sticky ends" on either side.
•Transposase inserts the TE into the new location (integration).
•Cellular repair mechanisms repair the NEW cleavage site.
oDNA polymerase I and DNA ligase repair the single-stranded
flanking sites.
oThis creates a direct repeat on either side of the inserted TE.
.

16. 16
Figure: 1.4
The original TE has moved to a new location.
There has been no duplication of the TE.

17. 17
Autonomous and Non-Autonomous Tranposons
A transposable element containing
owild type, functional inverted repeats
owild type, functional ORF sequence
...can both encode transposase and be recognized and moved by it.
This type of TE is said to be
 
autonomous.
An autonomous transposon can generate its own transposition.
A transposable element containing
omutant 
inverted repeats OR
omutant 
ORF sequence
.will have inverted repeats unrecognizable to transposase OR
mutant transposase that is non-functional.
This type of TE is said to be
 
non-autonomous.
A non-autonomous transposon cannot generate its own transposition.
It has become a permanent resident of its current DNA location.

18. 18
Figure: 1.5 : Autonomous and Non-Autonomous Tranposons

19. 19
Long Interspersed Nuclear Elements (LINES)
•It is a 6 kb (6x1000) long retroposon.
•LINEs are autonomous.
•They can create their own reverse transcriptase.
•Cause short target site duplication.
Figure: 1.6: LINEs

20. 20
Short Interspersed Nuclear Elements (SINES)
• It is the most abundant class of transposons in humans
•As their name implies SINES are short sequences s with maximum
size of 400 bp.
•They do not encode proteins needed for reverse transcription but
posses an internal promoter for RNA polymerase.
•They are not autonomous and so depend on LINES for
transposition.
Figure: 1.7: SINEs

21. 21
Conclusion
•Transposons are present in the genomes of all organisms, where they
can constitute a huge fraction of the total DNA sequence. They are a
major cause rearrangement, of mutations and genome
•The ability of transposable elements to insert and to generate deletions
and inversions accounts for much of the macromolecular
rearrangement,
•They cause mutation which is used in the production of different
colour of grapes, corn and other fruits,As a result they are used in the
genetic studies.

22. 22
Research articles:
•Benjaminlewin.Genes.1997.Newyork.Printed in USA.
•Daniel L.Hartl.Elizabeth.w.Jones., Genetics edition.2005.USAAnalysis of
genes and genomes. 6thBenjamin A.pierce.Genetics: A conceptual
approach.third edition.Newyork 2008.
•Monroe W.Stickberger.Genetics.thirdedition. 1985, USA.
• McClintock B. Controlling elements and the gene. Cold Spring Harb Symp
Quant Biol. (1956) 21:197–216. doi: 10.1101/SQB.1956.021.01.017
•Levin HL, Moran JV. Dynamic interactions between transposable elements
and their hosts. Nat Rev Genet. (2011) 12:615–27. doi: 10.1038/nrg3030
•Goodier JL, Kazazian HH Jr. Retrotransposons revisited: the restraint and
rehabilitation of parasites. Cell. (2008) 135:23–35. doi:
10.1016/j.cell.2008.09.022
Books:
•prescott.harley.klein;sixth edition international edition
2005;microbiology;page no-291-295.
•verma p.s.agarwal v.k; 2004; cell biology,genetics,molecular
biology,evolution and ecology;page no-254-260.
References :