Transposons
CA García Sepúlveda MD PhD
Laboratorio de Genómica Viral y Humana
Facultad de Medicina, Universidad Autónoma de San Luis
Potosí
1
Session #25-26 Transposons
Introduction
• Genomes evolve both by rearranging existing sequences and by
acquiring new sequences.
• Rearrangements are sponsored by internal genomic events.
– Unequal recombination (non-recirpocal) results from mispairing by the
cellular mechanisms for homologous recombination.
– Results in duplication or rearrangement of loci (Clusters & repeats).
– Duplication of sequences within a genome gives rise to further
duplication.
2
Session #25-26 Transposons
Introduction
• Genomes evolve both by rearranging existing sequences and
by acquiring new sequences.
• Results from the ability of vectors to carry information between genomes.
Plasmids move by conjugation.
Extrachromosomal elements move
information horizontally by
mediating the transfer of short
lengths of genetic material.
3
Session #25-26 Transposons
Introduction
• Genomes evolve both by rearranging existing sequences and
by acquiring new sequences.
• Results from the ability of vectors to carry information between genomes.
Phages spread by infection.
Both plasmids and phages
occasionally transfer host genes
along with their own replicon.
4
Session #25-26 Transposons
Introduction
• Genomes evolve both by rearranging existing sequences and
by acquiring new sequences.
• Results from the ability of vectors to carry information between genomes.
– Direct transfer of DNA occurs
between some bacteria by
means of transformation.
5
Session #25-26 Transposons
Introduction
• Genomes evolve both by rearranging existing sequences and
by acquiring new sequences.
• Results from the ability of vectors to carry information between genomes.
In eukaryotes, some viruses
(notably the retroviruses) can
transfer genetic information during
an infective cycle.
6
Session #25-26 Transposons
Introduction
• Genomes evolve both by rearranging existing sequences and
by acquiring new sequences.
• Another major cause of variation is provided by transposable elements
or transposons:
– these are discrete sequences in the genome that are mobile & able to
transport themselves to other locations within the genome.
– Found in both eukaryotes & prokaryotes.
– Selfish DNA with the sole purpose of autoreplication.
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Session #25-26 Transposons
Introduction
• Relationship of the transposon to the genome resembles that of a
parasite with its host.
• The propagation of an element by transposition is balanced by the harm
done if a transposition event inactivates a necessary gene.
• Any transposition event conferring a selective advantage will lead to
preferential survival of the genome harboring the transposon !
8
Session #25-26 Transposons
Transposons
• Transposons do not utilize an independent form (such as virus or plasmid
DNA).
• Move directly from one site of the genome to another.
• Unlike other processes involved in genome restructuring, transposition
does not rely on homology between donor and recipient sites.
• Sometimes transfer contiguous host sequences to new sites elsewhere
within the same genome as they move.
• They are an internal counterpart to the vectors that can transport
sequences from one genome to another.
9
Session #25-26 Transposons
Transposons
• Transposable elements can promote rearrangements of the genome,
directly or indirectly:
– Directly: The transposition event itself may cause deletions or
inversions or lead to the movement of a host sequence to a new
location.
– Indirectly: Transposon sequences serve as substrates for cellular
recombination systems by functioning as "portable regions of
homology";
• two copies of a transposon at different locations (even on different
chromosomes) may provide sites for reciprocal recombination
resulting in deletions, insertions, inversions, or translocations.
10
Session #25-26 Transposons
Transposons
• They may provide the major source of mutations in the genome!
• Two general classes of transposons:
– DNA transposons
Exist as sequences of DNA coding for proteins that are able directly to
manipulate DNA so as to propagate themselves within the genome.
– RNA transposons
They are related to retroviruses and move as a consequence of their
ability to make DNA copies of their RNA transcripts, the DNA copies
then become integrated at new sites in the genome.
11
Session #25-26 Transposons
Transposons
• Transposons carry gene(s) that code for the enzyme activities
required for their own transposition.
• However, it may also require host machinery (DNA pol or DNA gyrase).
12
Session #25-26 Transposons
Discovery
• Transposable elements were first identified in the form of spontaneous
insertions in bacterial operons.
• Such an insertion prevents transcription and/or translation of the gene in
which it is inserted.
• The first transposons that were discovered were simple and called
insertion sequences (IS).
• Each type is given the prefix IS, followed by a number that identifies the
type. The original classes were IS1-4, more classes have been
discovered since.
• Insertion into a particular site described with a double colon:
l::IS1 = An IS1 element inserted into phage lambda.
13
Session #25-26 Transposons
Insertion Sequences (IS)
• IS elements are normal constituents of bacterial chromosomes &
plasmids.
• A standard strain of E. coli contains
<10 copies of the more common IS
elements.
• The IS elements code only for the
proteins needed to sponsor its own
transposition.
• Each IS element is different in
sequence, but there are common
organizational features.
14
Session #25-26 Transposons
Insertion Sequences (IS)
• An IS element ends in short inverted terminal repeats which are not
identical but closely related.
• Inverted repeats recognized by
TRANSPOSASE.
• Ensure that the same sequence is
encountered proceeding toward the
element from any direction.
• Inverted repeat recognition is
common to transposition events
sponsored by all transposons.
• Cis-acting mutations of these ends prevent transposition.
15
Session #25-26 Transposons
Insertion Sequences (IS)
• When an IS element transposes, a sequence of host DNA at the site of
insertion is duplicated: DIRECT REPEATS.
•
IS DNA is always flanked by very
short direct repeats with the same
direction.
• Pre-transposition genomic sequences
exhibit only one of these “repeats”
(i.e.: ATGCA).
• Post-transposition sequence will
have this sequence duplicated and
flanking the transposon sequence.
16
Session #25-26 Transposons
Insertion Sequences (IS)
• IS display a characteristic structure in which its ends possess inverted
terminal repeats while the adjacent ends of the flanking host DNA
possess short direct
repeats.
• This type of organization is
taken to be diagnostic and suggest
that the sequence originated in a
transposition event.
• IS elements insert at a variety
of sites within host DNA, some show
preference for particular hotspots
17
Session #25-26 Transposons
Insertion Sequences (IS)
• All IS elements (except IS1) contain a single long coding region for
transposase starting after the inverted repeat at one end and terminating
before or within the
inverted repeat at the other end.
• IS1 is more complex, it employs
two separate reading frames.
• Frequency of transposition varies
amongst the different elements.
18
Session #25-26 Transposons
Insertion Sequences (IS)
• What would happen if an IS transposed near the original position... or if
two IS sequences were separated by genomic DNA?
• These transposons are called COMPOSITE TRANSPOSONS (Tn).
19
Session #25-26 Transposons
Composite Transposons (Tn)
• Code for more than proteins involved in transposition.
• A central genomic “core” flanked by two IS.
20
Session #25-26 Transposons
Composite Transposons (Tn)
• Central region discovered initially as carrying
drug markers or drug resistance traits.
• IS modules ("arms") may have same or
inverted orientations (most common).
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Session #25-26 Transposons
Composite Transposons (Tn)
• Central region discovered initially as carrying
drug markers or drug resistance traits.
• IS modules ("arms") may have same or
inverted orientations (most common).
• In some cases the modules are identical
– Tn9 (direct repeats of IS1)
– Tn903 (inverted repeats of IS903).
In other cases, the modules are only closely related (Tn10, Tn5).
22
Session #25-26 Transposons
Composite Transposons (Tn)
• A functional IS module can transpose either
itself or the entire transposon.
• Either identical module of a composite
transposon can sponsor movement (IS10L or
IS10R).
• In transposons with different modules
transposition might depend entirely or
principally on one of the modules (Tn10 or
Tn5).
• What is responsible for transposing a
composite transposon instead of just the
individual module?
23
Session #25-26 Transposons
Composite Transposons (Tn)
1.- IS vs Tn equally feasible & useful from a
“selfish point of view”.
2.- Selective pressure.
24
Session #25-26 Transposons
Composite Transposons (Tn)
1.- IS vs Tn equally feasible & useful from a
“selfish point of view”.
2.- Selective pressure.
– Two IS elements can transpose any
sequence residing between them just as
well as themselves.
– Exemplified by transposons in bacteria
where the two modules can be considered
to flank either the tetR gene of the original
Tn10 or the genomic sequence in the other
part of the circle.
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Session #25-26 Transposons
Composite Transposons (Tn)
1.- IS vs Tn equally feasible & useful from a
“selfish point of view”.
2.- Selective pressure.
– Selection for the trait(s) carried in the
central region.
– An IS10 module mobilizes an order of
magnitude more frequently than Tn10.
– But Tn10 is held together by selection for
tetR; so that under selective conditions, the
relative frequency of intact Tn10
transposition is higher.
26
Session #25-26 Transposons
Composite Transposons (Tn)
– The insertion of a transposon into a new
site consists of:
• Making staggered breaks in the target DNA
• Joining the transposon to the protruding singlestranded ends
• Filling in the gaps.
The stagger between the cuts determines the length of the direct repeats and
reflects the geometry of the enzyme involved in cutting target DNA.
27
Session #25-26 Transposons
Composite Transposons (Tn)
– The insertion of a transposon into a new
site consists of:
• Making staggered breaks in the target DNA
• Joining the transposon to the protruding singlestranded ends
• Filling in the gaps.
28
Session #25-26 Transposons
Composite Transposons (Tn)
– The insertion of a transposon into a new
site consists of:
• Making staggered breaks in the target DNA
• Joining the transposon to the protruding singlestranded ends
• Filling in the gaps.
The generation and filling of the staggered ends explain the direct repeats of
target DNA at the site of insertion.
The use of staggered ends is common to all transposons!
29
Session #25-26 Transposons
Composite Transposons (Tn)
– Three different types of mechanism by
which a transposon moves:
– Replicative Transposition
– Common Non-replicative Transposition
– Conservative Non-replicative Transposition
30
Session #25-26 Transposons
Composite Transposons (Tn)
– Three different types of mechanism by
which a transposon moves:
– Replicative Transposition
• The element is duplicated during the
reaction, so that the transposing entity
is a copy of the original element.
• One copy remains at the original site,
while the other inserts at the new site.
• Transposition is accompanied by an
increase in the number of copies.
31
Session #25-26 Transposons
Composite Transposons (Tn)
– Three different types of mechanism by
which a transposon moves:
– Replicative Transposition
• Involves two types of enzymatic activity:
– Transposase that acts on the ends
of the original transposon.
– Resolvase that acts on the
duplicated copies.
32
Session #25-26 Transposons
Composite Transposons (Tn)
– Three different types of mechanism by
which a transposon moves:
– Non-Replicative Transposition
• Two types:
– Common Non-replicative
Transposition.
– Conservative transposition (now
known as Episomal transposition
or simply Episome).
33
Session #25-26 Transposons
Composite Transposons (Tn)
– Three different types of mechanism by
which a transposon moves:
– Non-Replicative Transposition
• The transposing element moves as a
physical entity directly from one site to
another
– without copies
– without change
– Requires only a Transposase
• Tn10 & Tn5
34
Session #25-26 Transposons
Composite Transposons (Tn)
– Three different types of mechanism by
which a transposon moves:
– Common Non-Replicative Transposition
• Disregards double strand cleavage of
genomic DNA from which it originated.
• Relies on host repair mechanisms to
repair double strand breaks.
35
Session #25-26 Transposons
Composite Transposons (Tn)
– Three different types of mechanism by
which a transposon moves:
– Conservative Non-replicative
Transposition
• the element is excised from the donor
site and inserted into a target site by a
series of events in which every
nucleotide bond is conserved.
• Transposon looking after the health of
its host.
• Mechanism of lambda Phage
integration.
36
Session #25-26 Transposons
Composite Transposons (Tn)
– Three different types of mechanism by
which a transposon moves:
– Conservative Non-replicative
Transposition
• The elements that use this mechanism
are large, and can mediate transfer of
donor DNA from one bacterium to
another.
• Although originaly transposons, more
appropriate name is Episomes.
37
Session #25-26 Transposons
Composite Transposons (Tn)
– Transposons may use only one or different
types of pathway for transposition.
– Basic reactions involved in all classes of
transposition event:
• The ends of the transposon are
disconnected from the donor DNA by
cleavage reactions that generate 3’-OH
ends.
• The exposed ends are joined to the
target DNA by trans-esterification in
which the 3’-OH end directly attacks the
target DNA.
38
Session #25-26 Transposons
Composite Transposons (Tn)
• Reactions take place within nucleoprotein
complex (enzymes and both ends of the
transposon).
• Target site is chosen by transposase
(random vs. specificity)
– for a consensus sequence,
– for a structure, such as bent DNA,
– for inactive regions of the chromosome.
39
Session #25-26 Transposons
Composite Transposon DNA rearrangements
– Transposons promote other types of DNA rearrangements.
– Some of these events are consequences of the multiple copies
generated (gene duplications).
– Others represent alternative outcomes of the transposition
mechanism.
40
Session #25-26 Transposons
Composite Transposon DNA rearrangements
– Rearrangements of host DNA may result
when a transposon inserts a copy at a
second site near its original location.
– Host (or transposon) systems may
undertake reciprocal recombination
between the two copies of the transposon.
– The consequences are determined by
whether the repeats are the same or in
inverted orientation.
41
Session #25-26 Transposons
Composite Transposon DNA rearrangements
– Recombination between direct repeats will
delete the material between them.
– The intervening region is excised as a
circle of DNA (which is lost from the cell).
– The chromosome retains a single copy of
the direct repeat.
– A recombination between the directly repeated IS1 modules of the
composite transposon Tn9 would replace the transposon with a single
IS1 module… This doesn’t normally happen! Why?
42
Session #25-26 Transposons
Composite Transposon DNA rearrangements
– Excision is not supported nor coded by
transposons themselves.
– Mechanism is not known.
– Excision is RecA-independent.
– Might occur by some cellular mechanism
that generates spontaneous deletions
between closely spaced repeated
sequences.
43
Session #25-26 Transposons
Composite Transposon DNA rearrangements
– Reciprocal recombination between a pair
of inverted repeats.
– The region between the repeats becomes
inverted.
– The repeats themselves remain available
to sponsor further inversions.


A composite transposon whose modules are inverted is a stable component
of the genome, although the direction of the central region with regard to the
modules could be inverted by recombination.
Direction influences transcription and translation!
44
Session #25-26 Transposons
Composite Transposon DNA rearrangements
– Reciprocal recombination between a pair
of inverted repeats.
– The region between the repeats becomes
inverted.
– The repeats themselves remain available
to sponsor further inversions.


A composite transposon whose modules are inverted is a stable component
of the genome, although the direction of the central region with regard to the
modules could be inverted by recombination.
Direction influences transcription and translation!
45
Session #25-26 Transposons
Transposition Intermediates
– Many mobile DNA elements transpose from
one chromosomal location to another by a
fundamentally similar mechanism.
• IS elements
• Prokaryotic & eukaryotic transposons
• Bacteriophage Mu.
• Retroviral RNA integration.
• The first stages of
immunoglobulin
recombination.
46
Session #25-26 Transposons
Transposition Intermediates
– Transposon is nicked at both ends.
– Target sequence is nicked at both ends.
47
Session #25-26 Transposons
Transposition Intermediates
– The nicked ends are joined crosswise to
generate a covalent connection between the
transposon and the target.
– The two ends of the transposon are brought
together in this process.
– FIGURE NOTE: for simplicity in following the
cleavages, the synapsis stage is shown after
cleavage, but actually occurs BEFORE
CLEAVAGE.
48
Session #25-26 Transposons
Transposition Intermediates
– A more realistic image
– The strand transfer
complex in which the
transposon is connected to
the target site through one
strand at each end.
– The next step of the
reaction differs and
determines the type of
transposition.
49
Session #25-26 Transposons
Transposition Intermediates
– A more realistic image
– The strand transfer
complex can be a target
for replication (leading to
replicative transposition).
– Or the strand transfer
complex can be a target
for repair (non-replicative
transposition).
50
Session #25-26 Transposons
Transposition Intermediates
– A more realistic image
– The strand transfer
complex can be a target
for replication (leading to
replicative transposition).
– Or the strand transfer
complex can be a target
for repair (non-replicative
transposition).
51
Session #25-26 Transposons
Bacteriophage Mu (μ)
– Upon infecting a host cell, Mu
integrates into the genome by nonreplicative transposition.
52
Session #25-26 Transposons
Bacteriophage Mu (μ)
– Upon infecting a host cell, Mu
integrates into the genome by nonreplicative transposition.
– During the ensuing lytic cycle, the
number of copies is amplified by
replicative transposition.
53
Session #25-26 Transposons
Bacteriophage Mu (μ)
– Upon infecting a host cell, Mu
integrates into the genome by nonreplicative transposition.
– During the ensuing lytic cycle, the
number of copies is amplified by
replicative transposition.
– Both types of transposition involve the
same type of reaction between the
transposon and its target, but the
subsequent reactions are different.
54
Session #25-26 Transposons
Bacteriophage Mu (μ)
– The initial
manipulations of the
phage DNA are
performed by MuA
transposase.
55
Session #25-26 Transposons
Bacteriophage Mu (μ)
– Three MuA-binding
sites with a 22 bp
consensus are located
at each end of Mu
DNA.
– A monomer of MuA can
bind to each site.
– MuA also binds to an
internal site in the
phage genome
(enhancer).
– Binding of MuA at both the left and right ends and the internal site forms
a strand transfer complex.
56
Session #25-26 Transposons
Bacteriophage Mu (μ)
– Joining the Mu
transposon DNA to a
target site passes
through 3 stages.
– This involves only the
two sites closest to
each end of the
transposon.
– MuA has two sites for manipulating DNA:
• The consensus-binding site binds to the 22 bp sequences that
constitute the L1, L2, R1, and R2 sites.
57
Session #25-26 Transposons
Bacteriophage Mu (μ)
– Joining the Mu
transposon DNA to a
target site passes
through 3 stages.
– This involves only the
two sites closest to
each end of the
transposon.
– MuA has two sites for manipulating DNA:
• The active site cleaves the Mu DNA strands at positions adjacent to
the MuA-binding sites L1 and R1.
58
Session #25-26 Transposons
Bacteriophage Mu (μ)
– Joining the Mu
transposon DNA to a
target site passes
through 3 stages.
– This involves only the
two sites closest to
each end of the
transposon.
– MuA has two sites for manipulating DNA:
• The active site cannot cleave the DNA sequence that is adjacent to
the consensus sequence it can ONLY DO SO on a different stretch
of DNA (Trans acting).
59
Session #25-26 Transposons
Bacteriophage Mu (μ)
– MuB + ATP + Target
– A second protein, MuB,
assists the reaction.
– It has an influence on
the choice of target
sites.
– Mu has a preference for transposing to a target site >10-15 kb away
from the original insertion (target immunity).
– Not a very good use of energy to move only a couple of base pairs
down the road!
60
Session #25-26 Transposons
Replicative Transpositon
– Replicative transposition by definition generates a
copy of a transposon at a new site.
– The process (in circular replicons) proceed
through the formation of a COINTEGRATE or
hybrid structure.
– The process is explained by the Shapiro Model.
61
Session #25-26 Transposons
Replicative Transpositon
– A plasmid with a transposon is the donor molecule.
• Note transposon in black
• Note flanking direct repeats
– A bacterial chromosome is the recipient.
• Note the integration site
• No repeats here yet
– The process starts with the formation of the strand
transfer complex (crossover complex).
62
Session #25-26 Transposons
Replicative Transpositon
– NICKING takes place creating single strand cuts in
both the transposon (3'end) and recipient (5'end).
– Nicking depends on TRANSPOSASE.
63
Session #25-26 Transposons
Replicative Transpositon
– NICKING takes place creating single strand cuts in
both the transposon (3'end) and recipient (5'end).
– Nicking depends on TRANSPOSASE.
– 3'-end of the transposon is linked to 5'end of
recipient forming a Cointegrate hybrid.
64
Session #25-26 Transposons
Replicative Transpositon
– NICKING takes place creating single strand cuts in
both the transposon (3'end) and recipient (5'end).
– Nicking depends on TRANSPOSASE.
– 3'-end of the transposon is linked to 5'end of
recipient forming a Cointegrate hybrid.
– Sequence gaps are filled in by host replicative
machinery (repair DNA Pols) using exposed 3'-OH
as primers.
• Generates integration site direct repeats
65
Session #25-26 Transposons
Replicative Transpositon
– Replicated transposon exists at two sites now.
– As both transposons are similar they promote
homologous recombination between the two copies.
– The recombination reaction is called resolution and is
catalyzed by an enzyme called the resolvase.
66
Session #25-26 Transposons
Replicative Transpositon
– Replicated transposon exists at two sites now.
– As both transposons are similar they promote
homologous recombination between the two copies.
– The recombination reaction is called resolution and is
catalyzed by an enzyme called the resolvase.
– Resolution releases two individual replicons, each of
which has a copy of the transposon.
• One in the original donor replicon.
• A second one in the target replicon.
67
Session #25-26 Transposons
Non-Replicative Transpositon
– In non-replicative transposition the
cointegrate structure is never stabilized.
– Tranposon is completely excised before
transfer.
– Donor molecule remains nicked (and
perhaps repaired by host machinery).
– Staggered cuts in the recipient after
transposition are filled in by repair machinery.
68
Session #25-26 Transposons
Non-Replicative Transpositon
– Non-replicative transposition can also use
double-strand breaks to completely excise
the transposon before ligation.
– Host repair machinery is still needed to fill in
sequence gaps.
69
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– Certain strains of D. melanogaster encounter
difficulties in interbreeding.
– When flies from two of these different strains
are crossed, the progeny display "dysgenic
traits".
– Dysgeneic Traits are a series of defects
including:
• mutations,
• chromosomal aberrations,
• distorted segregation at meiosis, and
• sterility.
70
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– Hybrid Dysgenesis only appears when F1 is
the product of specific matings:
P Strain Males + M Strain Females
– Nothing happens when F1 is the product of
other types of matings:
M Strain Males + P Strain Females
• P Strains = Paternally contributing
• M Strains = Maternally contributing
71
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– Dysgenesis is principally a phenomenon of
the germ cells.
– In crosses involving the P-M system, the F1
hybrid flies have normal somatic tissues.
– However, their gonads do not develop.
– The morphological defect in gamete
development dates from the stage at which
rapid cell divisions commence in the
germline.
72
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– Transposition responsible for hybrid
dysgenesis occurs by a non-replicative "cut
and paste" mechanism:
– It contributes to hybrid dysgenesis in two
ways:
• Insertion of the transposed element at a
new site may cause mutations.
• And the break that is left at the donor site
has a deleterious effect.
73
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– Why is there a direction?
P♂ + M♀ = HD
M♂ + P♀ = Wt
74
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– Why is there a direction?
P♂ + M♀ = HD
M♂ + P♀ = Wt
– P♂♀ have 30-50 P elements (transposons)
– M♂♀ do not.
– P elements code for P factors (transposase)
in both P♂♀.
75
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– P elements code for P factors in both P♂♀.
– P element has 4 ORFs (exons).
– Somatic tissues only transcribe 3 exons.
– Germline cells transcribe 4 exons.
– Short polypeptide is 66KD and Represor.
– Long polypeptide is 87 kD and Transposase
76
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– Presence of Represor in cytoplasm inhibits
activity of Transposase in nucleous.
– This explains why P♂♀ flies are normal.
– P♂♀ flies can interbreed without problems
because the function of cytoplasmic and
nuclear transposon expression is balanced.
– But P♂♀ flies encounter breeding difficulty with
M♂♀ flies... in certain ways.
77
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– First, sperm differs from eggs in the amount of
cytoplasm (cytotope).
– Second, P♀ fly eggs possess both the
translocon and enormous amounts of
cytoplasm
repressor > transposase
– P♀ fly + M♂ fly = Progeny with P Cytotope
Normal
repressor > transposase
78
Session #25-26 Transposons
Transposons & Hybrid Dysgenesis
– P♂ fly sperm on the other hand possess little if
any cytoplasm & the same translocon
repressor < transposase
– Yet P♂ fly somatic cells have maternal P
cytotpe and are therby normal.
– P♂ fly + M♀ fly = Progeny with M Cytotope
Hybrid
Dysgenesis
repressor < transposase
79
Session #25-26 Transposons
Transposons & Humans
– The most common form of transposon in humans is the Alu sequence.
– Classified as short interspersed nuclear elements (SINEs) amongst the class
of repetitive DNA elements.
– Named for its susceptibility to Alu restriction endonuclease.
– Approximately 300 bases long and can be found between 300,000 & a million
times in the human genome.
– Alu sequences of different kinds occur in large numbers in primate genomes.
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Session #25-26 Transposons
Transposons & Humans
What percentage of human genome consists of Alu sequence type transposons?
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Session #25-26 Transposons
Transposons & Humans
What percentage of human genome consists of Alu sequence type transposons?
10.7%
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Session #25-26 Transposons
Transposons & Humans
– NCBI Map Viewer BLAST for Alu.
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Session #25-26 Transposons
Transposons & Humans
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Session #25-26 Transposons
Transposons & Humans
Go to Alu Jump Flash animation
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Session #25-26 Transposons
Transposons & Humans
– The common SINE (a type of retroposon)
family Alu probably originated from a
duplication of a 7SL RNA gene, member of
the SRP.
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Session #25-26 Transposons
Transposons & Humans
– Transposons are mutagens.
– They can damage the genome of their host cell in different ways:
• It inserts itself into a functional gene commonly disabling it.
• Replicative transposition leaves gaps.
• Multiple copies of the same sequence (Alu repeats) can lead to
unequal crossovers.
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Session #25-26 Transposons
Transposon related Hemophilia
– Group of hereditary genetic disorders that impair the body's ability to
control blood clotting or coagulation.
– Hemophilia A, clotting factor VIII is absent, in B factor IX is deficient.
– Type A occurs in about :5,000-10,000 male births, B occurs at about 1 in
about 20,000-34,000.
– Sex-linked, X chromosome disorder manifested almost entirely in males
but inherited from the mother.
– Major complications include hemarthrosis, hemorrhage, gastrointestinal
bleeding, and menorrhagia.
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Session #25-26 Transposons
Transposons & Disease
– Diseases that are often caused by transposons include:
• Hemophilia A and B
• Severe combined immunodeficiency
• Porphyria
• Predisposition to cancer
• Duchenne muscular dystrophy.
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Session #25-26 Transposons
Conclusion




Many changes in the genetic material are known to be deleterious.
In general terms, the more dramatic the change the more catastrophic
the outcome.
Rearrangements of DNA have traditionally been viewed as unnatural
and dangerous.
Discovery of transposons has given us a far more dynamic
perspective on genome evolution within which segments of DNA
naturally move about.
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Session #25-26 Transposons
Conclusion
The difference in genome size observed betwen the different lifeforms are
thought to be the result (in large part) of transposon activity.
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Session #25-26 Transposons
Conclusion
•Additionally, transposon-dependent genome rearrangements help explain
a mechanism of speciation, which furthers natural diversity (as clearly
demonstrated for D. melanogaster).
• Flies isolated more than 30 years ago almost always M strains.
• Flies isolated in the last 10 years mostly P strains.
–Mechanism for reproductive isolation plays an important role in the
evolution of novel species.
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Session #25-26 Transposons
Barbara McClintock (1983)
One of the world's most distinguished
cytogeneticists.
First to document many fundamental genetic ideas
under the microscope, including genetic
recombination by chromosomal crossover during
meiosis.
Produced the first genetic map for maize.
Demonstrated the role of the telomere &
centromere.
Discovered Dissociator & Activator Transposition
(~Hybrid dysgenesis in Maize)
Barbara McClintock
(Jun 16, 1902 – Sept 2, 1992).
1983 Nobel laureate in Physiology & Medicine
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