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Transposons

An introduction to transposons

• Transposons are sequences of DNA that can move around to different positions within
the genome of a single cell, a process called transposition. In the process, they can cause
mutations and change the amount of DNA in the genome.
• They were discovered by Barbara McClintock early in her career, for which she was
awarded a Nobel prize in 1983.
• The human genome project revealed that less than 5% of the human genome is likely to
consist of functioning genes. Of the remaining 95% of non-functioning genes, nearly
50% is thought to consist of transposable elements or transposons.
• Transposons are often referred to as “jumping genes” as they are segments of DNA
which are able to “jump” from location to location within a genome. This "jumping"
process is called transposition.
• Transposons are very useful to researchers as a means to alter DNA inside of a living
organism. Transposons make up a large fraction of genome sizes which is evident
through the C-values of eukaryotic species.

Figure showing
simple transposons

This example exhibits most of the


characteristics of simple transposons. The grey bars at each end represent the genomic DNA into
which the transposon is inserted. The yellow bars indicate a short stretch (~5 bp) of genomic
DNA that's repeated on either side of the insertion element. This short repeat is almost always
associated with insertion and excision of the transposon and it's a diagnostic feature of mobile
genetic elements. The red bars are inverted repeats at the ends of the transposon. This is another
feature that's common to most transposons and it is required for copying and insertion/excision.
This particular example contains a gene for the enzyme "transposase" (green).

Applications

The first transposon was discovered in the plant maize (Zea mays, corn species), and is named
dissociator (Ds). Likewise, the first transposon to be molecularly isolated was from a plant
(Snapdragon). Appropriately, transposons have been an especially useful tool in plant molecular
biology. Researchers use transposons as a means of mutagenesis. In this context, a transposon
jumps into a gene and produces a mutation. The presence of the transposon provides a
straightforward means of identifying the mutant allele, relative to chemical mutagenesis methods.
Sometimes the insertion of a transposon into a gene can disrupt that gene's function in a
reversible manner; transposase-mediated excision of the transposon restores gene function. This
produces plants in which neighboring cells have different genotypes. This feature allows
researchers to distinguish between genes that must be present inside of a cell in order to function
(cell-autonomous) and genes that produce observable effects in cells other than those where the
gene is expressed. Transposons are also a widely used tool for mutagenesis of most
experimentally tractable organisms.

Types of Transposons:

DNA Transposons

Some of the simplest transposons, called DNA transposons, consist of DNA sequences which

code for an enzyme called transposase. Transposase is able to cleave a transposon from the

genome, transport it to a new location, and reinsert it into the genome. This process is called

conservative transposition. All prokaryotic transposons as well as some eukaryotic transposons

utilize conservative transposition.

Diagram of Conservative Transposition.

Examples of DNA Transposons:

Ac (Activator) Transposable Elements- Ac transposons were one of the first transposable

elements discovered by Barbara McClintock within the maize corn genome. McClintock

discovered that Ac transposons are self-sufficient in that they code for their own transposase

enzyme and, therefore, can transpose independently.


Ds (Dissociator) Transposable Elements- Ds transposons were one of the first transposable

elements discovered by Barbara McClintock in the maize corn genome. McClintock discovered

that Ds transposons are non-autonomous, as they are unable to transpose independently. Ds

transposons do not code for their own transposase enzyme so they must depend on excess

transposase produced by nearby Ac transposons. Therefore, Ds transposons remain immobile

without the assistance of Ac transposons.

Retrotransposons

The majority of eukaryotic transposable elements are more complex transposons called

retrotransposons. The host cell recognizes the retrotransposon as a normal DNA sequence within

its genome, and synthesizes an RNA copy of it. However, the retrotransposon codes for an

enzyme called reverse transcriptase which is able to convert the RNA copy of the retrotransposon

into an exact DNA duplicate of the original. Transposase (which has been coded for by the

retrotransposon) then finds a suitable location to insert the new retrotransposon into the genome.

This process is called replicative transposition. If a retrotransposon is left functional, replicative

transposition will produce multiple copies of the retrotransposon within the genome.

Diagram of Replicative Transposition

There are two main types of retrotransposons.

Viral Retrotransposons

Viral retrotransposons have properties very similar to that of retroviruses.


Examples:

Ty Transposable Elements- The best known examples of Ty transposable elements can

be found within the yeast genome. During transposition, the Ty element is very prone to

mutation. As a result, there are many variations of Ty transposons passed down through

generations. One of these variations, the Ty1 transposon is present in 35 copies

throughout the yeast genome. The Ty transposable element causes harmful mutations by

being inserted into, and disrupting, various genes within the yeast genome.

Drosophilacopia Transposable Elements- The Drosophilacopia transposable element is

found within the drosophila (fruit fly) genome. There are seven known families of

Drosophilacopia transposons within the fruit fly genome, each of which has 10-100

copies within the genome. All together, Drosophilacopia transposons comprise 15% of

the Drosophila (fruit fly) genome. The Drosophilacopia transposon is very similar in

structure to the Ty transposon in yeast. When inserted into the genome, the

Drosophilacopia transposon duplicates a number of DNA bases from the Drosophila

genome at either of its ends. The Drosophilacopia transposon causes mutations by being

inserted into functioning genes and disrupting their function and regulation. An example

of such a mutation is the White Apricot Mutation which causes a variation in the colour

of the fruit fly’s eyes.

Non-Viral Retrotransposons

Non-viral retrotransposons comprise the largest majority of mammalian transposons.

Examples:

LINEs- There are roughly 850 000 LINES, or long interspersed (transposable) elements,

within each human genome. Some cases of hemophilia are caused by the insertion of a

LINE transposon into a gene on the X chromosome which is partly responsible for the

clotting of blood.
SINEs- There are roughly 1 500 000 SINEs, or short interspersed (transposable)

elements, within each human genome. Among these are the Alu Transposable Elements.

Alu Elements- Alu elements are the most common transposable elements within the

human genome, making up more than 5%. It is believed that approximately 30-50 million

years ago, Alu elements spread rapidly throughout the primate genome. Although they

had lost the majority of their activity before the evolution of human-like apes, they are

still a popular source of research. Approximately 0.1% of human genetic diseases are

caused by the transposition of Alu elements within the genome.

The number of active transposons within an organism’s genome varies greatly

depending on species. In humans, only a miniscule amount of transposons remain active.

It is estimated that 50 LINE transposons and few, if any, DNA transposons remain

functional within the human genome. On the other hand, the mouse genome plays host to

an estimated 3000 active LINE transposons and many active DNA transposons. Transposons also

vary within plant species. The maize corn genome has doubled in length over the past 3

million years because of transposon replications and insertions.

The Effects of Transposons

Functional transposons pose an enormous risk to the genome because of their mobility

and instability. When a transposon relocates within the genome it may land on a vital gene,

disrupting its function. Or, the transposon may land near vital genes, causing them to be

erroneously activated or shut-down. No matter its defences, no organism is capable of restricting

every transposon. In humans, genetic diseases are sometimes caused by the transfer of a

transposon from one location to another within the genome during sperm/egg production. As a

result of the transposon's movement, a genetic mutation often arises, which may trigger the

developement of a genetic disease. Should the offspring mature, this genetic mutation will be

passed on to future generations.


The chart below shows a multitude of human genetic disorders which have been linked to

harmful retrotransposon insertions. The chart also shows the genes which were disrupted by such

retrotransposons, resulting in mutation.

However, the danger of transposons today is not often seen as an enormous concern.

With all of the precautions taken by our cells, transposition within the genome has become a

rather infrequent event. One scientist, named Kleckner, estimated that the rate of transposition

within the human genome is between 10-4 and 10-7 times per transposon present, per generation.

Future Prospects for Transposons in Research

Scientists are optimistic that transposons will prove to be more and more useful in future

scientific research and medical treatment. It is thought that transposons may prove useful as a

method of gene therapy. Transposons could be used as vectors to deliver new, properly

functioning genes, to replace faulty genes within a patient's genome.

Despite all of the optimistic talk of transposons and their great potential, there are still

many great hurdles which scientists have yet to overcome. For example, transposons are very

limited in the size of DNA which they are able to carry during transposition. This puts limitations

on the prospect of transposons being used to carry genes during gene therapy. As well, geneticists

have to be extremely careful in selecting the correct insertion site for a transposon vector during

gene therapy. A tiny mistake could result in the transposon vector disrupting important genes

upon insertion.

Transposons and Mutations

Transposons are mutagens. They can cause mutations in several ways:

• If a transposon inserts itself into a functional gene, it will probably damage it. Insertion
into exons, introns, and even into DNA flanking the genes (which may contain promoters
and enhancers) can destroy or alter the gene's activity.
• The insertion of a retrotransposon in the DNA flanking a gene for pigment synthesis is
thought to have produced white grapes from a black-skinned ancestor. Later, the loss of
that retrotransposon produced the red-skinned grape varieties cultivated today.
• Faulty repair of the gap left at the old site (in cut and paste transposition) can lead to
mutation there.
• The presence of a string of identical repeated sequences presents a problem for precise
pairing during meiosis. How is the third, say, of a string of five Alu sequences on the
"invading strand" of one chromatid going to ensure that it pairs with the third sequence in
the other strand? If it accidentally pairs with one of the other Alu sequences, the result
will be an unequal crossover — one of the commonest causes of duplications.

SINEs (mostly Alu sequences) and LINEs cause only a small percentage of human mutations.
(There may even be a mechanism by which they avoid inserting themselves into functional
genes.) However, they have been found to be the cause of the mutations responsible for some
cases of human genetic diseases, including:

• Hemophilia A (Factor VIII gene) and Hemophilia B [Factor IX gene]


• X-linked severe combined immunodeficiency (SCID) [gene for part of the IL-2 receptor]
• porphyria
• predisposition to colon polyps and cancer [APC gene]
• Duchenne muscular dystrophy [dystrophin gene]

Transposons and the C-value Paradox

• The genome of Arabidopsis thaliana contains 1.2 x 108 base pairs (bp) of DNA. About
14% of this consists of transposons; the rest functional genes (about 25,000 of them).
• The maize (corn) genome contains 20 times more DNA (2.4 x 109 bp) but surely has no
need for 20 times as many genes. In fact, 60% of the corn genome is made up of
transposons. (The figure for humans is 44%.)
• Most of the 2.5 x 1011 bp of DNA in the genome of Psilotum nudum is presumably "junk"
DNA.

So it seems likely that the lack of an association between size of genome and number of
functional genes — the C-value paradox — is caused by the amount of transposon DNA
accumulated in the genome

Tn 10 is a transposable element, which is a sequence of DNA that is capable of mediating its own
movement through the DNA of host organisms. This fragment of DNA can move from position
to position on the chromosome or plasmid by cut-and-paste transposition (also known as 'non-
replicative transposition'). The Tn10 transposon is often used in genetics to transfer and select-for
genes of interest from one organism into the chromosome of another.

Being a composite transposon, it is flanked by insertion sequences. In Tn9 the insertion


sequences are oriented in the same direction as each other, but in Tn5 and Tn10 the insertion
sequences are symmetrical. Between the Tn10 insertion sequences, there are a number of genes,
including one conferring resistance to the antibiotic, tetracycline. This phenotype makes tn10
convenient as a genetic tool. A gene of interest is inserted into the transpson and the transposon is
then transferred to new host cells. The gene of interest is then 'selected-for' by exposing these
cells to tetracycline, thus eliminating any cells that did not successfully take up the transposon.

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