2. INTRODUCTION
Transposable elements are also known as
“TRANSPOSONS” , “JUMPING GENES” ,
“MOBILE GENETIC ELEMENTS”.
These are DNA sequences able to transport
themselves to other location within the
genome.
1st transposable element was discovered by
Barbara McClintock in maize in 1950.
Term was given by “Hedges and Jacob(1947).
3. Cont……
They can insert new copies of themselves
throughout the genome.
Each transposable element carries transposase
gene that encodes for enzyme activity required
for its own transposition.
They are “specific” sequence of DNA present in
~40% of the genomic DNA.
They are found in the genomes of many kinds of
organisms.
They are also called controlling elements as they
affect gene expression.
4. DISCOVERY OF MOBILE
GENETIC ELEMENT
The 1st transposable element was
discovered by “Barbara McClintock
(1902-1990)” in Maize in late 1940s.
Her discovery of jumping genes, through
an analysis of genetic instability in
Maize, earn her noble prize in 1983 in
Physiology or Medicine.
The instability involves chromosome
breakage and was found to occur at sites
where transposable elements were
located i.e. at C locus of 9th
chromosome.
Barbara McClintock
5. Origin of Junk DNA Hypothesis
The idea that a large portion of the genomes of eukaryotes is
made up of useless evolutionary remnants comes from the
problem known as the ‘c- value paradox’, ‘c’ meaning the
haploid chromosomal DNA content.
There is an extraordinary degree of variation in genome size
between different eukaryotes, which does not correlate with
organismal complexity or the numbers of genes that code for
proteins.
Early DNA-RNA hybridization studies and recent genome
sequencing results have confirmed that >90 % of the DNA of
vertebrates does not code for a product.
Much of this variation is due to non-coding (i.e. not producing
an RNA or protein product), often very simple, repeated
sequences.
6. Cont….
With the discovery that many of these sequences seemed to
have arisen from mobile DNAs which are able to reproduce
themselves, the selfish or parasitic DNA hypothesis was
born.
However, recent research has begun to show that many of
these useless-looking sequences do have a function, and that
they may have played a role in ‘with in kind’
diversification.
Types of Junk DNA:
1. introns, internal segments in genes that are removed at the
RNA level;
2. pseudogenes, genes inactivated by an insertion or deletion;
3. satellite sequences, tandem arrays of short repeats; and
4. interspersed repeats, which are longer repetitive sequences
mostly derived from mobile DNA elements.
7. Mobile DNA Element: Overview
Mobile genetic elements include transposon,
which move within a single cell (and its
descendants), plus those viruses whose
genomes can integrate into the genomes of
their host cells.
In bacteria, transposable elements can move to
new positions on the same chromosome
(because there is only one chromosome) or
onto plasmids or phage chromosomes; in
eukaryotes, transposable elements may move
to new positions within the same chromosome
or to a different chromosome.
8. Cont……
In both bacteria and eukaryotes, transposable
elements insert into new chromosome
locations with which they have no sequence
homology; therefore, transposition is a process
different from homologous recombination
(recombination between matching DNA
sequences)and is called non-homologous
recombination.
9. Cont….
Transposable elements are important due to the
genetic changes they cause. For example, they can
produce mutations by inserting into genes (a process
called insertional mutagenesis),they can increase or
decrease gene expression by inserting into gene
regulatory sequences (such as by disrupting promoter
function or stimulating a gene’s expression through
the activity of promoters on the element), and they
can produce various kinds of chromosomal mutations
through the mechanics of transposition.
In fact, transposable elements have made important
contributions to the evolution of the genomes of both
bacteria and eukaryotes through the chromosome
rearrangements they have caused.
10. Rate of transposition, induction and
defense
One study estimated the rate of transposition of a
particular retrotransposon, the Ty1 element in
Saccharomyces cerevisiae came out to be about once
every few months to once every few years.
Cells defend against the proliferation of TEs in a number
of ways. These include piRNAs and siRNAs, which
silence TEs after they have been transcribed.
If organisms are mostly composed of TEs, one might
assume that disease caused by misplaced TEs is very
common, but in most cases TEs are silenced through
epigenetic mechanisms like DNA methylation, chromatin
remodeling and piRNA, such that little to no phenotypic
effects nor movements of TEs occur as in some wild type
plant TEs.
11. Cont…..
Although each kind of transposable element has its own
special characteristics, most can be classified into one of
three categories based on how they transpose.
12. Cont….
The cut-and-paste transposons are found in both
prokaryotes and eukaryotes. The replicative
transposons are found only in prokaryotes, and
the retro-transposons are found only in
eukaryotes.
CUT AND PASTE TRANSPOSITION
A cut-and-paste transposon is excised from one
genomic position and inserted into another by an
enzyme, the transposase, which is usually
encoded by the transposon itself.
The element is physically cut out of one site in a
chromosome and pasted into a new site, which
may even be on a different chromosome.
14. Cont….
REPLICATIVE TRANSPOSITION
Transposition is accomplished through a process that
involves replication of the transposable element’s DNA.
A transposase encoded by the element mediates an
interaction between the element and a potential insertion
site.
During this interaction, the element is replicated, and one
copy of it is inserted at the new site; one copy also remains
at the original site.
RETROTRANSPOSITION
Involves the insertion of copies of an element that were
synthesized from the element’s RNA.
An enzyme called reverse transcriptase uses the element’s
RNA as a template to synthesize DNA molecules, which are
then inserted into new chromosomal sites.
16. Transposable Elements in Prokaryotes
Bacterial transposons move within and between chromosomes
and plasmids.
Main Types:
1. IS Elements or the Insertion Sequences
2. The Composite transposons and
3. The Tn3 like elements.
4. IS Elements and Transposons in Plasmids
5. Bacteriophage Mu
These three types of transposons differ in size and structure.
The IS elements are the simplest, containing only genes that
encode proteins involved in transposition.
The composite transposons and Tn3-like elements are more
complex, containing some genes that encode products
unrelated to the transposition process.
17. IS ELEMENTS
The IS elements are normal constituents of bacterial
chromosomes and plasmids. Among bacteria as a
whole, the IS elements range in size from 768 bp to
more than 5,000 bp and are found in most cells.
All IS elements end with perfect or nearly perfect
terminal inverted repeats (IRs) of 9 to 41 bp. This
means that essentially the same sequence is found at
each end of an IS, but in opposite orientations.
Figure: Structure of an inserted IS50element showing its terminal inverted repeats and
target site duplication. The terminal inverted repeats are imperfect because the fourth
nucleotide pair (highlighted) from each end is different.
18. Integration of ‘IS’ element in
chromosomal DNA
IS elements usually encode a protein, the transposase, that is
needed for transposition. The transposase binds at or near the
ends of the element and then cuts both strands of the DNA.
This cleavage excises the element from the chromosome or
plasmid, so that it can be inserted at a new position in the
same or a different DNA molecule. IS elements are therefore
cut-and-paste transposons.
When IS elements insert into chromosomes or plasmids, they
create a duplication of part of the DNA sequence at the site of
the insertion.
One copy of the duplication is located on each side of the
element.
These short (2 to 13 nucleotide pairs), directly repeated
sequences, called target site duplications, arise from
staggered cleavage of the double-stranded DNA molecule.
20. Cont…..
When a particular IS element
resides in two different DNA
molecules, it creates the
opportunity for homologous
recombination between them. For
instance, an IS element in the F
plasmid may pair and recombine
with the same kind of IS element
in the E. coli chromosome.
When an IS element mediates
recombination between these
molecules, the smaller plasmid is
integrated into the larger
chromosome, creating a single
circular molecule. Such
integration events produce Hfr
strains capable of transferring
their chromosomes during
conjugation.
Figure: Formation of a conjugative
R plasmid by recombination between
IS elements.
21. THE COMPOSITE TRANSPOSON
Composite transposons are created when two IS elements insert
near each other. The region between the two IS elements can then
be transposed when the elements act jointly. In effect, the two IS
elements “capture” a DNA sequence that is otherwise immobile and
endow it with the ability to move.
Composite transposons, like the IS elements that are part of them,
create target site duplications when they insert into DNA.
Composite transposons carry genes (e.g., antibiotic resistance) flanked
on both sides by IS elements (IS modules).
i. The IS elements are of the same type, and called ISL (left) and ISR
(right).
ii. ISL and ISR may be in direct or inverted orientation to each other.
iii. Tn10 is an example of a composite transposon (Figure 20.3). It is 9.3
kb, and contains:
(1) 6.5 kb of central DNA with genes that include tetracycline resistance
(a selectable marker).
(2) 1.4 kb IS elements (IS10L and IS10R) at each end, in an inverted
orientation.
22. Cont…..
iv. Transposition of
composite transposons
results from the IS
elements, which
supply transposase and
its recognition signals,
the IRs.
(1) Tn10’s
transposition is rare,
because transpose is
produced at a rate of ,1
molecule/generation.
(2) Transposons, like
IS elements, produce
target site duplications
23. The Tn3 Element
Bacteria contain other large transposons that do not
have IS elements at each of their ends. Instead, these
transposons terminate in simple inverted repeats 38
to 40 nucleotide pairs long; however, like the cut-
and-paste transposons, they create target site
duplications when they insert into DNA.
They also carry genes (e.g., drug resistance) but do
not terminate with IS elements.
i. Transposition proteins are encoded in the central
region.
ii. The ends are repeated sequences (but not IS
elements).
iii. Cause target site duplications (like composite
transposons).
24. Cont….
Tn3 has three genes in its central region:
(a) bla encodes β-lactamase, which breaks down ampiciliin.
(b) tnpA encodes transposase, needed for insertion into a new
site.
(c) tnpB encodes resolvase, involved in recombinational events
needed for transposition (not found in all transposons).
Tn3 produces a 5-bp duplication upon insertion
25. Tn3 is a replicative transposon that moves in a two-stage process.
Figure: Transposition of Tn3 via
the formation of a co-integrate.
26. IS Elements and Transposons in Plasmids
1. Bacterial plasmids are extrachromosomal DNA capable of self-replication. Some
are episomes, able to integrate into the bacterial chromosome. The E. coli F
plasmid is an example (Figure 20.7):
a. Important genetic elements of the F plasmid are:
i. tra genes for conjugal transfer of DNA from donor to recipient.
ii. Genes for plasmid replication.
iii. 4 IS elements: 2 copies of IS3, 1 of IS2, and 1 of γδ (gammadelta). All have
homology with IS elements it the E. coli chromosome.
b. The F factor integrates by homologous recombination between IS elements,
mediated by the tra genes.
2. R plasmids have medical significance, because they carry genes for resistance to
antibiotics, and transfer them between bacteria (Figure 20.7).
a. Genetic features of R plasmids include:
i. The resistance transfer factor region (RTF), needed for conjugal transfer. It includes
a DNA region homologous to an F plasmid region, and genes for plasmid-specific
DNA replication.
ii. Differing sets of genes, such as those for resistance to antibiotics or heavy metals.
The resistance genes are transposons, flanked by IS module-like sequences, and
can replicate and insert into the bacterial chromosome.
b. R plasmids are clinically significant, because they disseminate drug resistance
genes between bacteria.
28. Bacteriophage Mu
1. Temperate bacteriophage Mu (mutator) can cause mutations when it
transposes.
Its structure includes:
a. A 37 kb linear DNA in the phage particle that has central phage DNA
and unequal lengths of host DNA at the ends (Figure 20.8).
b. The DNA’s G segment can invert, and is found in both orientations in
viral DNA.
2. Following infection, Mu integrates into the host chromosome by
conservative (non-replicative) transposition.
a. Integration produces prophage DNA flanked by 5 bp target site direct
repeats.
b. Flanking DNA from the previous host is lost during integration.
c. The Mu prophage now replicates only when the E. coli chromosome
replicates, due to a phage-encocled repressor that prevents most Mu
gene expression.
3. Mu prophage stays integrated during the lytic cycle, and replication of
Mu’s genome is by replicative transposition.
4. Mu causes insertions, deletions, inversions and translocations
29. Fig. Temperate bacteriophage Mu genome shown in (a) as in phage particles and
(b) as integrated into the E. coli chromosome as a prophage
30. Fig. Production of deletion or inversion by homologous recombination
between two Mu genomes or two transposons
31. Transposable Elements in Eukaryotes
1. Rhoades (1930s) working with sweet corn, observed
interactions between two genes:
a. A gene for purple seed color, the Al locus. Homozygous
mutants (a/a) have colorless seeds.
b. A gene on a different chromosome, Dt (dotted) that causes
seeds with genotype a/a Dt/-- to have purple dots.
i. Dt appears to mutate the a allele back to the Al wild-type in
regions of the seed, producing a dotted phenotype.
ii. The effect of the Dt allele is dose dependent.
(1) One dose gave an average of 7.2 dots per seed.
(2) Two doses gave an average of 22.2 dots/seed.
(3) Three doses gave an average of 121.9 dots/seed.
c. Rhoades interpreted Dt as a mutator gene.
32. Cont….
2. McClintock (1940s-50s), working with corn (Zea mays)
proposed the existence of “controlling elements” that
regulate other genes and are mobile in the genome.
3. The genes studied by both Rhoades and McClintock have
turned out to be transposable elements, and many others
have been identified in various eukaryotes.
a. Most studied are transposons of yeast, Drosophila, corn and
humans.
b. Their structure is very similar to that of prokaryotic
transposable elements.
c. Eukaryotic transposable elements have genes for
transposition and integration at a number of sites, as well as
a variety of other genes.
d. Random insertion results from non-homologous
recombination, and means that any chromosomal gene may
be regulated by a transposon.
33. Transposons in Plants
1. Plant transposons also have IR sequences, and generate short direct
target site repeats.
2. The result of transposon insertion into a plant chromosome will depend
on the properties of the transposon, with possible effects including:
a. Activation or repression of adjacent genes by disrupting a cellular
promoter, or by action of transposon promoters.
b. Chromosome mutations such as duplications, deletions, inversions,
translocations or breakage.
c. Disruption of genes to produce a null mutation (gene is nonfunctional).
3. Several families of transposons have been identified in corn, each with
characteristic numbers, types and locations.
a. Each family has two forms of transposon. Either can insert into a gene
and produce a mutant allele.
i. Autonomous elements, which can transpose by themselves. Alleles
produced by an autonomous element are mutable alleles, creating
mutations that revert when the transposon is excised from the gene.
34. Cont….
ii. Nonautonomous elements, which lack a transposition gene
and rely on the presence of another transposon to supply the
missing function. Mutation by these elements is stable
(except when an autonomous element from the family is also
present).
4. Multiple genes control corn color, and classical genetics
indicates that a mutation in any of these genes leads to a
colorless kernel. McClintock studied the unstable mutation
that produces spots of purple pigment on white kernels.
a. She concluded that spots do not result from a conventional
mutation, but from a controlling element (now Tn).
b. A corn plant with genotype c/c will have white kernels, while
C/-- will result in purple ones.
i. If a reversion of c to C occurs in a cell, that cell will produce
purple pigment, and hence a spot.
ii. The earlier in development the reversion occurs, the larger
the spot.
35. Cont….
iii. McClintock concluded that the c allele resulted from
insertion of a “mobile controlling element” into the C allele.
(1) The element is Ds (dissociation), now known to be a non-
autonomous transposon.
(2) Its transposition is controlled by Ac (activator), an
autonomous transposon.
c. McClintock’s evidence of transposable elements did not fit
the prevailing model of a static genome. More recent studies
have confirmed and characterized the elements involved.
i. The Ac-Ds system involves an autonomous element (Ac)
whose insertions are unstable, and a non-autonomous
element (Ds) whose insertions are stable if only Ds is
present.
ii. McClintock (1950s) showed that some Ds elements derive
from Ac elements.
37. Cont….
iii. Ac is 4,563 bp, with 1 1-bp imperfect terminal IRs and
1 transcription unit producing a 3.5 kb mRNA encoding
an 807 amino acid transposase. Insertion generates an 8-
bp target site duplication (Figure 20.12).
iv. Ac activates Ds to transpose or break the chromosome
where it is inserted.
v. Ds elements vary in length and sequence, but all have
the same terminal IRs as Ac, and many are deleted or
rearranged versions of Ac.
vi. Unique to corn transposons, timing and frequency of
transposition and gene rearrangements are
developmentally regulated.
38. Cont….
vii. Ac transposes only during chromosome replication,
and does not leave a copy behind. There are two
possible results of Ac transposition, depending on
whether the target DNA has replicated or not .
(1) If Ac transposes during replication into a replicated
target site, its chromatid’s donor site will be empty
since that copy of Ac has inserted elsewhere. In the
homologous donor site on the other chromatid, a copy
will remain. There is no net increase in copies of Ac.
(2) Transposition to an unreplicated chromosome site also
leaves one donor site empty (and the other with a copy
of Ac). The DNA into which Ac inserts will then be
replicated, resulting in a net gain of one copy of Ac.
viii. Replication of Ds is the same, except that the
transposition protein is supplied by an integrated Ac
element.
39. Fig. The structure of the Ac autonomous transposable element of corn and of
several Ds nonautonomous elements derived from Ac
41. Cont…..
5. In Mendel’s wild-type (SS) peas the starch grains
are large and simple, while in wrinlded peas (ss)
they are small and fissured.
a. SS seeds contain more starch and less sucrose
than ss seeds.
b. The sucrose difference makes ss seeds larger,
with higher water content, so that when dried they
are wrinided.
c. One type of starch-branching enzyme (SBEI) is
missing in ss plants, reducing their starch content.
d. The SBEI gene corresponding to the s allele has a
0.8 kb transposon similar to the Ax/Ds family
inserted into the wild type S allele.
42. Ty Elements in Yeast
1. Ty elements share characteristics with bacterial transposons:
a. Terminal repeated sequences.
b. Integration at non-homologous sites.
c. Generation of a target site duplication (5 bp).
2. Ty element is diagrammed in Figure 20.14:
a. It is 5.9 kb including 2 terminal direct repeats of 334 bp, the long terminal repeats
(LTR) or deltas (δ).
b. Each delta contains a promoter and transposase recognition sequences.
c. Ty elements encode one 5.7 kb mRNA beginning at the delta 5’promoter.
d. There are two ORFs in the mRNA, designated TyA and TyB, encoding two different
proteins.
e. Ty copy number varies between yeast strains, with an average of about 35.
43. Cont….
3. Ty elements also share similarities with retroviruses,
ssRNA viruses that replicate via dsDNA intermediates.
a. Ty elements transpose by making an RNA copy of the
integrated DNA sequence, them making DNA using
reverse transcriptase. This DNA can integrate at a new
chromosomal site. Evidence for this includes:
i. An experimentally introduced intron in the Ty element
(which normally lacks introns) was monitored through
transposition. The intron was removed, indicating an
RNA intermediate.
ii. Ty elements encode a reverse transcriptase.
iii. Virus-like particles containing Ty RNA and reverse
transcriptase activity occur.
b. Ty elements are referred to as retrotransposons.
44. RETROVIRUSES
Retrovirus genomes are composed of single-stranded RNA
comprising at least three genes: gag (coding for structural
proteins of the viral particle), pol (coding for a reverse
transcriptase/integrase protein), and env (coding for a protein
embedded in the virus’s lipid envelope).
Retroviruses are distinguished from other types of
retroelements by the presence of an env gene in their genome.
The protein encoded by this gene allows retroviruses to enter
and leave their host cell.
Retroviruses are therefore the only infectious type of
retroelement: they spread from cell to cell, and also organism
to organism.
pol gene also has a DNA polymerase activity, which enables it
to synthesize a duplex DNA from the single- stranded reverse
trancript of the RNA. The enzyme has an RNase H activity,
which can degrade RNA part of RNA-DNA hybrid.
46. LTR Retrotransposons
Both LTR retrotransposons and retroviruses are
characterized by the presence of about 300- to 500- bp long
direct repeats at both ends of the element.
These so called LTRs contain control sequences for the
initiation and termination of transcription as well as for
polyadenylation.
DNA between the LTRs is normally between 3 and 5 kb long.
It encodes a capsid protein, an RNase H, a reverse
transcriptase, a protease and an endonuclease which serves as
an integrase.
LTR retrotransposons can be classified into two groups that are
distinguished by the arrangement of the integrase and reverse
transcriptase genes along the element.
47. Cont….
These groups were
named Ty 1- copia and
Ty 3-gypsy, respectively
following the
nomenclature given to
the initial representatives
of both groups, which
were first described for
yeast (transposon
yeast:Ty 1 and Ty 3) and
Drosophila (copia and
gypsy).
Both types of
retroelements are
ubiquitous in many plant
species.
48. Non- LTR Retrotransposons
Retrotransposons lacking the terminal repeats. They can be
further divided into LINEs and SINEs.
LINEs
Several kilobases long, have a chracteistic poly(A) tract at
their 3’ end, and are by flanked by short direct repeats (3 to
16 bp) that result from the repair of the staggered breaks
generated by the integration process
Two open reading frames are usually present, one encoding
a capsid protein, and the other encoding an endonuclease
and a reverse transcriptase domain.
Plant LINEs generally exhibit high levels of sequence
heterogeneity, which may be the consequence of the
accumulations of mutations in these mostly defective
elements.
49. Cont….
SINEs
With about 100 to 500 bp, SINEs are much smaller than
LINEs.
They are not able to transpose on their own, but require the
activity of a reverse transcriptase in trans.
SINEs are derived from processed pseudogenes.
Their intact ancestors are host genes encoding small
cytoplasmic RNAs such as tRNAs.
Like LINEs, SINEs are flanked by short target site
duplications and harbor an A- rich tract at their 3’ end.
Like their tRNA progenitors, SINEs carry two internal
promotersrecognised by host RNA polymerase II.
50. Drosophila transposons
1. It is estimated that 15% of the Drosophila genome is mobile!
These transposons fall into different classes:
a. The copia retrotransposons include several families, each
highly conserved and present in 5-100 widely scattered copies
per genome
i. All copia elements in Drosophila can transpose, and there are
differences in number and distribution between fly strains.
ii. Structurally, copia elements are similar to yeast Ty elements:
(1) Direct LTRs of 276 bp flank a 5 kb DNA segment.
(2) The end of each LTR has 17 bp inverted repeats.
(3) An RNA intermediate and reverse transcriptase are used for
transposition.
(4) Virus-like particles (VLPs) occur with copia.
(5) Integration results in target site duplication (3-6 bp).
51. Fig. Structure of the transposable element copia, a retrotransposon
found in Drosophila melanogaster
52. Cont….
b. P elements cause hybrid dysgenesis, a series of
defects (mutations, chromosomal aberrations and
sterility) that result from crossing certain
Drosophila strains.
i. A mutant lab strain female (M) crossed with a wild-
type male (P) will result in hybrid dysgenesis.
ii. A mutant lab strain male (M) crossed with a wild-
type (P) female (reciprocal cross) will have normal
offspring.
iii. Thus, hybrid dysgenesis results when
chromosomes of the P male parent enter cytoplasm
of an M type oocyte, but cytoplasm from P oocytes
does not induce hybrid dysgenesis.
54. Cont….
iv. The model is based on the observation that the M strain has no P
elements, while the haploid genome of the P male has about 40 copies.
(1) P elements vary from full-length autonomous elements through shorter
versions resulting from a variety of internal deletions.
(2) P element transposition is activated only in the germ line.
(3) The F1 of an M female crossed with a P male have P elements inserted
at new sites, flanked by target site repeats.
(4) P elements are thought to encode a repressor protein that prevents
transposase gene expression, preventing transposition.
(5) Cytoplasm in an M oocyte lacks the repressor, and so when fertilized
with P-bearing chromosomes, transposition occurs into the maternal
chromosomes, leading to hybrid dysgenesis.
v. P elements are used experimentally to transfer genes into the germ line
of Drosophila embryos. For example (Figure 20.18):
(1) The wild-type rosy (ry) gene was inserted into a P element, cloned in a
plasmid and microinjected into a mutant ry/ry strain.
(2) Insertion of the recombinant P element into the recipient chromosome
introduced the ry allele, and produced wild-type flies.
55. Fig. Structure of the autonomous P transposable element found in
Drosophila melanogaster
56. Fig. 20 Illustration of the use of P elements to introduce genes into the Drosophila genome
57. HUMAN RETROTRANSPOSONS
1. Alu1 SINEs (short-interspersed sequences)
~300 bp long, repeated 300,000-500,000X.
Flanked by 7-20 bp direct repeats.
Some are transcribed, thought to move by RNA
intermediate.
AluI SINEs detected in neurofibromatosis
(OMIM1622200) intron; results in loss of an
exon and non-functional protein.
58. Cont…
2. L-1 LINEs (long-interspersed sequences)
6.5 kb element, repeated 50,000-100,000X
(~5% of genome).
Contain ORFs with homology to reverse
transcriptases; lacks LTRs.
Some cases of hemophilia (OMIM-306700)
known to result from newly transposed L1
insertions.
60. TRANSPOSONS AND GENOME ORGANIZATION
Some genomic regions are especially rich in transposon
sequences.
In Drosophila, for example, transposons are concentrated in
the centric heterochromatin and in the heterochromatin abutting
the euchromatin of each chromosome arm.
However, many of these transposons have mutated to the point
where they cannot be mobilized; genetically, they are the
equivalent of “dead.” Heterochromatin therefore seems to be a
kind of graveyard filled with degenerate transposable elements.
Several Drosophila transposons have been implicated in the
formation of chromosome rearrangements, and a few seem to
rearrange chromosomes at high frequencies.
One possible mechanism is crossing over between homologous
transposons located at different positions in a chromosome.
If two transposons in the same orientation pair and cross over,
the segment between them will be deleted
61.
62. Cont….
Crossing over can also occur between transposons
located in different chromosomes.
If we consider a case where the crossover involves two
sister chromatids. Each chromatid carries two
neighboring transposons oriented in the same direction.
The transposon on the left in one chromatid has paired
with the transposon on the right in the other chromatid.
A crossover between these paired transposons yields
two structurally altered chromatids, one lacking the
segment between the two transposons, the other with an
extra copy of this segment.
Crossing over between neighboring transposons can
therefore duplicate or delete chromosome segments—
that is, it can expand or contract a region of the
genome.
63.
64. TRANSPOSABLE ELEMENTS AND EVOLUTION
TEs are found in most life forms, and the scientific
community is still exploring their evolution and their effect
on genome evolution.
It is unclear whether TEs originated in the last universal
common ancestor, arose independently multiple times, or
arose once and then spread to other kingdoms by horizontal
gene transfer.
Various viruses and TEs also share features in their genome
structures and biochemical abilities, leading to speculation
that they share a common ancestor.
Because excessive TE activity can damage exons, many
organisms have developed mechanisms to inhibit their
activity.
Bacteria may undergo high rates of gene deletion as part of a
mechanism to remove TEs and viruses from their genomes,
while eukaryotic organisms typically use RNA interference
to inhibit TE activity.
65. Cont….
Nevertheless, some TEs generate large families often
associated with speciation events. Evolution often
deactivates DNA transposons.
Large quantities of TEs within genomes may still
present evolutionary advantages, however. Interspersed
repeats within genomes are created by transposition
events accumulating over evolutionary time.
Because interspersed repeats block gene conversion,
they protect novel gene sequences from being
overwritten by similar gene sequences and thereby
facilitate the development of new genes.
TEs can contain many types of genes, including those
conferring antibiotic resistance and ability to transpose
to conjugative plasmids.
66. TRANSPOSONS AND DISEASES
TEs are mutagens and their movements are often the causes
of genetic disease. They can damage the genome of their
host cell in different ways:
A transposon or a retrotransposon that inserts itself into a
functional gene will most likely disable that gene;
After a DNA transposon leaves a gene, the resulting gap
will probably not be repaired correctly;
Multiple copies of the same sequence, such as Alu
sequences, can hinder precise chromosomal pairing during
mitosis and meiosis, resulting in unequal crossovers, one of
the main reasons for chromosome duplication.
Diseases often caused by TEs include haemophilia A and B,
severe combined immunodeficiency, porphyria,
predisposition to cancer, and Duchenne muscular dystrophy.
67. Significance of transposable elements
Genetic significance
Contributes to more than half the DNA in Maize genome.
Johng Lim observed the role of T.E
-in evolution of chromosome structure
-in chromosomal rearrangements
Spontaneous mutations caused by T.E insertions such as P,
retrovirus like elements & retroposons e.g mobilized P
elements in Dysgenic hybrids of Drosophila.
Evolutionary issues
T.E are nature’s tool for genetic engineering. as –have
ability to copy, transpose & rearrange other sequences.
Can spread simply as
-replicate selfishly independent of normal replication
machinery.
-act as genomic parasites.
