Transposons are the mobile genetic sequences that change its position within the genome, by transposition, a new copy of the gene generated at a new location.

These transposon sequences are class of the intermediate repeat sequences which are similar to each other but are not identical.

The human genome is made up of the coding sequences and non-coding sequences. The coding sequences are gene sequences encodes for a particular protein while the non-coding sequences are just a junk of the genome.

These non-coding sequences do not code for any proteins.

The non-coding sequences are repeated DNA sequences located on the satellite regions of a chromosome.

The transposons are such a class of repeated sequences which are intermediately repeated and interspersed between coding sequences.

In this present valuable theoretical article, we will discuss all the details on the transposons.

Key topics:

Overview of the topic

History of transposons

Different types of transposons

LINEs SINEs Retrotransposons

Importance of transposons

Conclusion

Abbreviation used in this article

Abbreviation Full name DNA Deoxyribonucleic acid LINEs Long Interspersed Elements SINEs Short Interspersed Elements LTR Long Terminal Repeats UTR Untranslated Region MIR Mammalian wide-interspersed Repeats TE Transposable elements TSD Target site duplication TIR Terminal Inverted Repeats MITE Miniature Inverted Repeats mRNA Mature RNA

Overview of the topic:

Genes can not move.

Genes are fixed on the chromosomes. The overall structure of the genome is invariant. It is responsible for the development of a specific type of phenotype in an organism.

The location of a gene is very important for genetic mapping and analysis in the classical genetic.

However, after the discovery of the transposons, the myth broke.

The transposons are also called transposable elements which are mobile genetic sequences that can move from one place to another into the genome.

The transposon DNA sequences can actually change its position. These mobile genes are present both in prokaryotes and eukaryotes.

The transposons do not have any significant role in the genome, therefore, it is named as selfish or parasitic DNA.

Why it is selfish?

By the process of transposition, it produces a new copy of it at a new location into the genome and even this new copy cannot be removed.

The new gene copy cannot be easily removed because the removal of genetic material is a slower process and conserved since evolution.

The transposons are responsible for chromosomal breakage and therefore it is parasitic to the host genome.

Functionally it jumps from one place to another, into the genome and through duplication produce a new copy of it hence it is called a “jumping gene” too.

History of the transposons:

During the year 1944 and 1945, Barbara McClintock discovered the first transposons in the maize through genetic instability. She called it transposable elements.

She noticed that the chromosomal breakage occurred due to the presence of the mobile element at the site of the breakage.

For her discovery, B. McClintock awarded Nobel Prize in the year 1983 for Physiology and Medicine.

She named it as Ac-Ds types of transposable elements.

Her discovery is an important milestone in genetic science so it is very important to understand what she observed or discovered during her experiments.

Let’s understand her experiments,

The triploid endosperm of the Maize is made up of two maternal and one paternal nucleus. See the above figure.

The outermost layer of the endosperm called an aleuron, pigmentation in aleurons is responsible due to some of the transposons.

She selected a marker on a short arm of the chromosome 9 and named it as C. The CC genotype is responsible for the pigmentation on the aleurons.

Contrary, the C1 is the dominant inhibitor of the colouration on the endosperm.

She crossed both the types of plant and observed C1CC genotype in the F1 progeny.

Theoretically, the F1 progeny must contain colourless kernels. Although the F1 progeny contains the colourless kernels but not all.

Some of the kernels show brownish-purple colour on the outer layer of the endosperm.

In the presence of the C1 dominant inhibitor, none of the progenies should the colouration which means the C1 inhibitor gene is lost.

She concluded that during the endosperm development the C1 gene is lost due to genetic instability which produced such tissues that produce colour patches.

She named the genotype as “-CC” and postulated that the loss of the gene fragment occurred due to the chromosomal breakage.

She experimented several times and concluded that some factors present on chromosome 9 are responsible for the chromosomal breakage, she named it “Ds elements” or dissociation factor.

However, she noticed that these elements cannot be activated without a special class of the activators.

The activators help the Ds elements to induce the chromosomal breakage and lead to a transposition of some of the genes.

She named it as “Ac elements” or “Activator“.

This class of transposons are called as Ac-Ds transposable elements. However, she had noticed that apart from the Ac-Ds transposons there are other different transposable elements are present into the maize genome.

~90% of the maize genome is made up of the mobile jumping transposable elements. Further, 44% of the human genome is made up of the transposable elements.

“The Ac elements are functionally autonomous, self-activated whereas the Ds elements are functionally non-autonomous, required activators to do their function.”

What are transposons?

As we discussed earlier, the transposons are the mobile genetic elements.

Through the recombination, it moves from one place to another place at were by doing replication it produces a new copy of it and hence creates new mutation through the insertion.

So it can follow all the process as like the functional gene present into the genome but still, it is not considered as a part of the genome.

Because it can move even between two different genomes. Scientist now realises that some of the viruses are actually derived from the transposons that can move between two host genome.

On the other side, transposons such as retrotransposons can be integrated into the host genome and replicate efficiently. Although it is not a part of the host genome.

How can we say that the transposable elements are an integral part of an organism’s genome?

The transposons are less understood until now, their influence on a gene is lesser known.

Some of the characteristics of the transposons are enlisted below,

They are mobile genetic elements

Transposons are intermediately repeated sequences.

They might active or inactive.

They are replicative and non-replicative (create new copy through replication- replicative; move to another location but not replicate- non-replicative).

Mostly ubiquitous in nature.

It can jump through both DNA and RNA intermediates.

It does not affect the original function of a gene, directly.

It can interrupt gene expression.

Transposons in some of the species:

Specie % of transposons Human genome ~45% Mouse genome 37% Fish 10% C. elegans 12% Maize >80%

Interestingly, the transposons influence the function of the gene through deletion or insertion.

The process of recombination is responsible for such a malfunction.

If the two copies of transposons are in opposite direction, the gene segment between them is inverted.

If the two copies are in the same direction, the gene segment between them is deletion. Therefore, if the functional DNA sequence is present between the jumping gene, the deletion or insertion causes mutation.

And this is the reason why the transposons are parasitic to the host.

Different types of transposons:

The number of transposable elements and the types of it vary from species to species. In this section, we will discuss some of the prokaryotic and eukaryotic transposable elements.

Broadly the transposable element families are classified into the two classes:

DNA transposons

Retrotransposons

Retrotransposons:

The retrotransposons are occupied the larger portion of the eukaryotic genome.

They are continuously replicated by “copy and paste” mechanism. It replicates throughout the genome of the eukaryotes hence retrotransposons possesses the larger portion of the genome.

They are inserted into the genome through the reverse transcription mechanism.

First, it is transported to another position through recombination, converted into the RNA by transcription.

The retrotransposon jumps through an RNA intermediate. However, the RNA cannot be inserted into the genome.

So the RNA is reverse transcribed into the DNA with the help of the reverse transcriptase enzyme.

Once the DNA is formed it is inserted into the genome.

Now the same transposons move to other location into the genome.

Half of the retrotransposon contains long terminal repeats (LTRs). The long terminal repeats are present on both ends of the retrotransposon, approximately 1000 bp long.

The autonomous transposition of the retrotransposon is mediated by the proteins integrase, RNase H, proteinase and reverse transcriptase.

The “gag” and the “pol” genes present between the LTRs helps to encode these proteins. See the figure above.

Interestingly, the retrotransposon is very much similar to the retrovirus. The retrovirus contains an additional “env” gene for the formation of the envelope protein of the virus.

Therefore scientist believes that the LTR-retrotransposon is the origin of retrovirus.

Once the retrotransposon is formed it is inserted between the gene and makes it inactive.

More than 50% of the human genome is made up of the retrotransposon. Nonetheless, these sequences are endogenous and have been inactive since long.

The other half portion of the retrotransposon does not contain LTRs and so-called non-LTRs which is further categorised into LINEs and SINEs.

Read further:

LINEs:

The LINEs are Long Interspersed Elements found in the higher eukaryotes, 6 to 8 Kb long interspersed repeat retrotransposon.

The LINEs contains two open reading frames, ORF1 near the 3′ end and ORF2 adjacent to this. See the figure below,

It also contains the promoter region for the RNA polymerase (because it is involved in the reverse transcription).

The sequences present into the ORF1 encodes for the reverse transcriptase while the ORF2 encodes for the endonuclease.

The reverse transcriptase synthesis DNA from the mRNA template. Through the process called retrotransposition, the new copy of DNA inserted into the genome.

The 3′ end of the retrotransposon is AT-rich region from where the copying is started and due to this reason, the 5′ end of the LINEs remains truncated.

The LINEs subfamily, LINEs1, LINEs2, LINEs3 and LINEs4 contains ~20% of the human genome in which the LINEs1 contains 500,000 copies (~17%) of the total sequences.

SINEs:

SINEs are the main identity of the eukaryotic metazoan. The metazoa contains large numbers of the non-autonomous transposons called SINEs.

The SINEs are shorter transposons of 300 to 400bp having RNA polymerase III promoter region.

The sequences of the SINEs are similar to the (3′ end) sequences recognised by reverse transcriptase.

Most SINEs elements are non-autonomous.

When we are talking particularly for the human genome, the human genome contains three families of the SINEs elements.

Alu

MIR

MIR3

Most copies of the Alu transposons contain restriction sites for the Alu1 restriction endonuclease. Hence the name is derived from there.

Interestingly, 10% of the genome is made up of the Alu type of SINEs transposable elements.

It is the commonest types of jumping gene with about 106 copies into the genome.

The Alu is the only transposable elements which are still active into the genome. Though none of the sequences into the human genome are uniformly distributed, we can say that on an average after every 3kb of the sequence one Alu is present.

Instead of the tRNA gene, the Alu elements are derived from the 7SL RNA.

MIR and MIR3 contain the sequences similar to the 3′ end of the recognition sequence of the reverse transcriptase enzyme, however, the sequence hierarchy of the Alu element is different.

It does not carry such type of sequences. Therefore it is not clear that which reverse transcriptase leads the retrotransposition.

On the other side,

The MIR and MIR3 are different.

MIR- mammalian wide-interspersed elements are found in all mammals.

The reverse transcriptase (encoded by the LINEs 2) recognise the 50bp sequence present on the 3′ end of the MIR3, similar to its recognition site.

LINEs and MIR elements are inactive in the genome now.

The last active LINEs 3 elements were disappeared before 100 million years ago.

13% of the human genome is made up of Alu, MIR, MIR3 transposons.

LTR- retrotransposons:

The long terminal repeat retrotransposons are very much similar to the retrovirus.

It contains the gag and pol gene for the synthesis of integrase, RNase H and reverse-transcriptase.

Due to the presence of the gal and pol, the LTR-retrotransposons follow autonomous transposition.

Interestingly, the LTRs are very much similar to the retrovirus. The retrovirus contains only additional env gene for the coat protein.

The LTR derived retrotransposons contain ~8% portion of the genome. However, the transposons are inactivated since so long.

DNA transposons:

The transposons in the bacteria and some of the prokaryotes are types of DNA transposons. And these transposons are still active in their genome. The sequences between the terminal inverted repeats of DNA transposons encode for the protein called “transposonase” or “transposase“.

A transposase presents in bacteria gives antibiotic resistance power by “copy and paste” mechanism. This transposons move from one place to another by leaving the original transposons at its native position.

With it, if some extra gene of antibiotic resistance is carried, it gives superpower to bacteria for antibiotic resistance.

And this is the main reason why the multidrug resistance spread so rapidly.

Nonetheless, in the human genome, the DNA transposons have been inactive before 50 million years ago.

In human, it contains ~3% of the total genome. The DNA transposons are categorised into the Class 2 transposons.

Class I Transposons:

These are retrotransposons.

Required reverse transcriptase enzyme for the synthesis of DNA from the mRNA.

Actively found in the viruses although, inactively present into the eukaryotic genome too.

Class II Transposons:

These are DNA transposons required transpsase enzyme for transposition.

Transposition occurs directly from DNA to DNA.

Do not require reverse transcriptase enzyme.

It can capable of transporting additional gene too.

Actively present in the prokaryotes such as bacteria but inactive into the eukaryotic genome.

Now coming to the important point of this article,

Are transposons beneficial to us?

Since their discovery, they are declared as selfish or parasitic to the host genome. It only increases their numbers into the genome by “copy and paste” mechanism

And it is true in some extends. Why?

Beauce when it is inserted into the active gene, it hinders in the activity of that particular gene.

It may stop the activity of a gene or makes the faulty proteins, that is totally a random process.

However, any of the alterations occurred into the genome is for some cause. Therefore it might be helpful in future for us.

( but we don’t know how!)

It is said that the transposable elements were retrovirus in the past. However, it is a controversial topic to discuss. Still, gag and pol gene present in the retrotransposons favours the statements.

“Transposons are natural mutagens that create new mutation into the genome.”

So, it is possible in the future that if it is activated, it might cause lethal conditions to humans.

In this perspective, they are parasitic to the host genome.

Still, it promotes the translocation of DNA sequences from one place to another which ultimately creates genetic diversity in favour of an organism.

Apart from this, the transposable elements also involve in the double-stranded break repair. Further, it facilitates exon shuffling.

It creates new gene products and genotype (maybe) for the survival of an organism and that is the main role of the TEs throughout the evolution.

The TEs are the important elements for genetic diversity, gene regulation and evolution.

For bacteria, their selfishness is beneficial in some conditions. For some of the bacteria having a larger number of transposable elements can survive higher or develop rapid multi-drug resist as compared to the bacterial strains with fewer transposons.

In recent day science, we have adopted their capability for transferring some of the genes.

Yes, the transposons may carry some gene and transfer it to the desired location into the genome.

Also, they can fill chromosomal breakage or gaps by the autonomous transposition. Now, it is proved that these elements are parasitic as well as beneficial to the host genome.

Notwithstanding, 99% of human transposable elements are inactive now, still 1% of it is involved in some of the colon cancer and bleeding disorder.

In addition to this, the transposons can even induce chromosomal breakage. Remember the Ds element into the Maize!

The Ds elements in maize and P elements in the Drosophila are responsible for the chromosomal breakage and viz loss of the genetic material.

External resource on the role of TEs on in the evolution: Transposable Elements and Evolution

Importance of transposons:

We learn so many things about the transposable elements in this article but is it important to us? or can it be used as a tool in the research?

The answer is yes.

Both the type (type I and II) of transposons can produce another copy of the gene through recombination and replication. however, the type I transposons are doing it though RNA-mediated transposition.

But the purpose of both the type of transposition is to generate a new copy of the DNA.

However, if it inserted into the functional gene it interferes in the normal function of a gene by disrupting the coding sequence of it likewise it creates amorphic or null mutation.

It induces a new mutation into the genome.

Does anything strike in your mind?

Remember site-directed mutagenesis!!

Yes, the TEs can be utilised for the creation of artificial mutation in any of the genome.

The first TE was isolated from the snapdragon plan. especially, in the plants, it is used as a tool for the site-directed mutagenesis.

Transposons are widely used in the plant genomic research for inserting new gene segments into the plant genome.

The present book contains all the information on how the TEs are used in the plant research.

TE can jump between any gene therefore if we inserted any mutation along with it. the new mutation can be incorporated into the genome.

However, the TE mediated insertional mutagenesis creates more accurate mutation than deletion mutagenesis.

In humans, the use of the TE mediated gene therapy or mutagenesis is still restricted. Scientists are developing a novel transposon-mediated tag system for encountering the cancer genes.

One of the efforts is the “Sleeping Beauty transposon system“. We will discuss all of it in the next article.

Lewis and co-workers are the pioneers in the field of using TEs as site-directed mutagenesis.

Read our impressive article on Site-Directed Mutagenesis: Methods and Applications

Another important role they play for us is to work as a carrier of the genetic material.

The class II retrotransposons carry additional sequences to their 3′ end, transport it and insert it into new locations.

Besides, it transports some of the exon sequences, promoter or enhancer sequences to the new location and tries new combinations.

Trial and error mechanism:

As we discussed, TEs are a creator of diversity.

Though almost 99% of transposons are inactive now into the human genome, some Alu‘s can do it.

Alu like retrotransposons insert some of the primary transcript (mRNA) between introns.

Here, during the splicing of the introns, spliceosome, recognise it as host genome exon and instead of splicing it, translate it into a new protein.

See the figure below,

Explanation of figure:

Step 1: The Alu inserted between the intron 1.

Step 2: The pre- mRNA forms along with the pre-mRNA of the Alu. Introns are removed

Step 3: The mRNA is formed and with Alu.

Step4: The faulty protein is formed due to the presence of Alu.

And that is how new proteins are formed. If it is helpful it remains into the genome, if it is not, it will be discarded later on.

In the same manner, if it is inserted into the exon, it inactive that axon which is recognised as

intron by the spliceosome and remove it.

As a result, the faulty protein is formed or a loss of function mutation is created.

Another element such as LINEs 1 regulates gene expression without affecting the protein formation.

80% of genes in the human genome contains the L1 transposons. Longer the L1 element shorter the gene expression and vice-versa.

Some of the external resources that you can use to understand the present topic more accurately:

Summary of the article:

The transposons are mobile elements that can move from one place to another into the genome.

They are divided into the Type I and type II transposons.

The type I TEs are retrotransposons which perform transposition through the RNA mediated reverse transcription.

The Type II TEs are DNA transposons that do DNA mediated transposition.

The LINEs, SINEs and LTR- retrotransposons are a different class of retrotransposons.

TEs are natural mutagens that create a mutation at a different location through the loss of function mutation.

It facilitates the evolution of new variation into nature and regulates gene expression.

Almost 99% of the transposons into the human genome are now inactive.

bacteria transposons provide them with a power of antibiotic resistance.

Conclusion:

It is very difficult to decide whether the transposons are helpful to us or parasitic to us because most of the transposons are inactive into nature before 10 million years ago.

Scientists are trying hard to solve the mystery of the TEs. Still, there are many questions which are unanswerable to us.

Even we don’t know the origins of it. The TEs are originated from the retrotransposons but it is still just a hypothesis.

In this series of articles, we will cover so many topics related to transposons.

Upcoming articles:

Bacterial transposons and antibiotic resistance. DNA mediated transposition. Different type of transposons in different organisms. Transposons, evolution and speciation The transposon-mediated occurrence of disease.

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