Index
Barbara McClintock’s discovery of these jumping genes earned her a Nobel Prize in 1983.
A transposable element (TE or transposon) is a DNA sequence that can change its position within a genome, sometimes creating or reversing mutations and altering the cell’s genetic identity and genome size.
The rearrangement often results in the duplication of the same genetic material.
Transposable elements make up a significant fraction of the genome and are responsible for much of the DNA mass in a eukaryotic cell. Transposable elements are essential in genome function and evolution.
In Oxytricha, which has a unique genetic system, these elements play a critical role in development. Transposons are also valuable for researchers in altering DNA within a living organism.
There are at least two classes of transposable elements:
Class I transposable elements or retrotransposons generally function by reverse transcription. In contrast, Class II transposable elements or DNA transposons encode the transposase protein, which requires insertion and cleavage, and some of these transposable elements also encode other proteins.
Discovery
Barbara McClintock discovered the first transposable elements in corn (Zea mays) at the Cold Spring Harbor Laboratory. McClintock was experimenting with corn plants that had broken chromosomes.
In the winter of 1944-1945, McClintock planted corn kernels that were self-pollinated, meaning that the silk (style) of the flower received pollen from its anther.
These grains came from a long line of plants that had been self-pollinated, causing the arms to break at the end of their ninth chromosome.
As the corn plants began to grow, McClintock noticed unusual color patterns on the leaves. For example, one leaf had two albino patches of almost identical size, located next to each other on the leaf.
McClintock hypothesized that during cell division, specific cells lost genetic material while others gained what they lost.
However, when comparing the chromosomes of the current generation of plants with the leading generation, he discovered that certain parts of the chromosome had changed position.
This refuted the popular genetic theory of the time when genes were fixed in place on a chromosome. McClintock discovered that genes could not only move but could also be turned on or off due to specific environmental conditions or during different stages of cell development.
McClintock also showed that genetic mutations could be reversed. He presented his report on his findings in 1951 and published an article on his discoveries in Genetics in November 1953 entitled “Induction of instability at selected locations in corn.”
His work was discarded and largely ignored until the late 1960s-1970s, when it was rediscovered after transposable elements were found in bacteria.
He received the Nobel Prize in Physiology or Medicine in 1983 for discovering transposable elements more than thirty years after his initial research.
Approximately 90% of the maize genome comprises transposable elements, as is 44% of the human genome.
Classification
Transposable elements represent one of several types of mobile genetic elements.
According to their transposition mechanism, transparent items are assigned to one of two classes. They can be described as copy and paste (Class I transposable items) or cut and paste (Class II transposable items).
Class I (retrotransposons)
Class, I transposable elements are copied in two steps: First, they are transcribed from DNA to RNA, and the RNA produced is reverse transcribed to DNA. This copied DNA is inserted back into the genome at a new position.
The reverse transcription step is catalyzed by reverse transcriptase, which is often encoded by the transposable element. The characteristics of retrotransposons are similar to retroviruses, such as HIV.
Retrotransposons are commonly grouped into three main orders:
Retrotransposons, with long terminal repeats (LTRs), encode reverse transcriptase, similar to retroviruses.
Retroposons, are long intercalated nuclear elements (LINE, LINE-1, or L1), which encode reverse transcriptase but lack long terminal repeats, and are transcribed by RNA polymerase II.
Short interspersed nuclear elements (SINEs) do not encode reverse transcriptase and are transcribed by RNA polymerase III.
Note: retroviruses can also be considered transposable elements. For example, after converting retroviral RNA to DNA within a host cell, the newly produced retroviral DNA is integrated into the host cell’s genome.
These integrated DNAs are called proviruses. A provirus is a specialized form of eukaryotic retrotransposon, producing RNA intermediates that can leave the host cell and infect other cells.
The transposition cycle of retroviruses has similarities to that of prokaryotic transposable elements, suggesting a distant relationship between the two.
Class II (DNA transposons)
The cut-and-paste mechanism of transposition of class II transposable elements does not involve an intermediate RNA. Various transposase enzymes catalyze the rearrangements.
Some transposases do not specifically bind to any target site on DNA, while others bind to specific target sequences.
The transposase makes a staggered cut at the target site producing sticky ends, cuts the DNA transposon, and binds it to the target site.
A DNA polymerase fills in the gaps resulting from the sticky ends, and DNA ligase closes the sugar-phosphate backbone.
This results in duplication of the target site. The DNA transposon insertion sites can be identified by short, direct repeats (a staggered cut in the DNA polymerase-filled target DNA) followed by inverted repeats (which are essential for cleavage of the element. transposable by transposase).
Cut-and-paste transposable elements can be duplicated if transposition occurs during the S phase of the cell cycle when a donor site has already been replicated. However, a target site has not yet been replicated.
Such duplications at the destination site can result in gene duplication, which plays a vital role in genomic evolution.
Not all DNA transposons are transposed through cut and paste. In some cases, a replicative rearrangement is observed in which a transposon replicates itself at a new target site (e.g., helitron).
Class II transposable elements comprise less than 2% of the human genome, making the remainder Class I.
Autonomous and non-autonomous
The transposition can be classified as “autonomous” or “non-autonomous” in Class I and II transposable elements.
The autonomous transposable element can move by itself, whereas the non-autonomous transposable element requires the presence of another transposable element to move.
This is often because the dependent transposable element has no transposase (for Class II) and no reverse transcriptase (for Class I).
The activator element (Ac) is an example of a self-contained transposable element, and the dissociation elements (Ds) are an example of a non-autonomous transposable element. Without activating elements, the dissociation elements cannot be transposed.
Examples
The first transposable elements were discovered in corn (Zea mays) by Barbara McClintock in 1948, for which she was later awarded the Nobel Prize.
She noted the chromosomal insertions, deletions, and translocations caused by these elements. These changes in the genome could, for example, lead to a change in the color of corn kernels.
About 85% of the maize genome consists of transposable elements. The activator element/dissociation element system described by McClintock is a Class II transposable element.
The transposition of the activator element in tobacco has been demonstrated by B. Baker (Plant Transposable Elements, pp 161-174, 1988, Plenum Publishing Corp., ed. Nelson).
A family of transposable elements in the fruit fly Drosophila melanogaster are called P elements. They appear to have first appeared in the species only in the mid-20th century; in the last 50 years, they have spread throughout all populations of the species.
Gerald M. Rubin and Allan C. Spradling pioneered using artificial P elements to insert genes into Drosophila by injecting the embryo.
Transposons in bacteria generally carry an additional gene for functions other than transposition, often for antibiotic resistance.
In bacteria, transposons can jump from chromosomal DNA to plasmid DNA and back, allowing the transfer and permanent addition of genes such as those encoding antibiotic resistance (multiple antibiotic-resistant bacterial strains can be generated).
Bacterial transposons of this type belong to the Tn family. When the transposable elements lack additional genes, they are known as insertion sequences.
The most common transposable element in humans is the Alu sequence. It is approximately 300 bases long and can be found between 300,000 and one million times in the human genome.
Alu alone represents 15-17% of the human genome.
Sailor-like elements are another prominent class of transposons found in multiple species, including humans.
Jacobson and Hartl first discovered the Mariner transposon in Drosophila. This Class II transposable element is known for its extraordinary ability to transmit horizontally in many species.
An estimated 14,000 copies of Mariner in the human genome comprise 2.6 million base pairs. The first transposons of marine elements outside of animals were found in Trichomonas vaginalis.
These characteristics of the Mariner transposon inspired Bob Marr’s science fiction novel The Mariner Project.
Mu phage rearrangement is the best-known example of replicative rearrangement.
Yeast (Saccharomyces cerevisiae) genomes contain five distinct families of retrotransposons: Ty1, Ty2, Ty3, Ty4, and Ty5.
A helitron is a transposable element found in eukaryotes and is believed to replicate using a rolling circle mechanism.
In human embryos, two types of transposons combine to form non-coding RNA that catalyzes stem cell development.
During the early stages of a fetus’ growth, the embryo’s inner cell mass expands as these stem cells enumerate.
The increase in these types of cells is crucial since the stem cells later change their shape and give rise to all the cells in the body.
In mottled moths, a transposon in a gene called bark caused the moths’ wings to turn completely black.
This change in coloration helped moths blend into ash and dark areas during the Industrial Revolution.
In sickness
Transposable elements are mutagens, and their movements are often the causes of genetic diseases. They can damage the genome of their host cell in different ways:
A transposon or retrotransposon inserted 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 accurate chromosomal pairing during mitosis and meiosis, leading to uneven crossovers, one of the main reasons for chromosome duplication.
Diseases often caused by transposable elements include hemophilia A and B, severe combined immunodeficiency, porphyria, predisposition to cancer, and Duchenne muscular dystrophy.
LINE1 (L1) translatable elements reaching human Factor VIII have been shown to cause hemophilia, and insertion of L1 into the APC gene causes colon cancer, confirming that transposable elements play an essential role in the development of the disease.
Dysregulation of the transposable element can cause neuronal death in Alzheimer’s disease and similar tauopathies.
Furthermore, many transposable elements contain promoters that direct the transcription of their transposase. These promoters can cause aberrant expression of linked genes, causing mutant phenotypes or diseases.
Rate of transposition, induction, and defense
One study estimated the transposition rate of a particular retrotransposon, the element Ty1, in Saccharomyces cerevisiae.
Using various assumptions, the success rate of the transposition event per individual Ty1 element ranged from once every few months to once every few years.
Some transposable elements contain heat-shock promoters. Their transposition rate increases if the cell is under stress, thus increasing the mutation rate under these conditions, which could benefit the cell.
Cells defend themselves against the proliferation of transposable elements in several ways. These include Piwi-interacting RNA (piRNA) and small interfering RNA (siRNA), which silence transposable elements after transcribed.
If organisms are composed primarily of transposable elements, it can be assumed that disease caused by misplaced transposable elements is prevalent.
However, in most cases, the transposable elements are silenced through epigenetic mechanisms such as DNA methylation, chromatin remodeling, and RNA interacting with Piwi.
So little or no phenotypic effect or transposable element movements occur as in some transposable elements of wild-type plants.
Certain mutated plants have been found to have defects in methylation-related enzymes (methyltransferase) that cause transcription of transposable elements, affecting the phenotype.
One hypothesis suggests that only approximately 100 LINE1-related sequences are active, even though their sequences make up 17% of the human genome.
In human cells, the silencing of LINE1 sequences is triggered by an RNA interference (RNAi) mechanism.
Surprisingly, the RNAi sequences are derived from the 5 ‘untranslated region (UTR) of LINE1, a long term that repeats itself.
The 5 ‘LINE1 untranslated region encoding the sense promoter for LINE1 transcription also encodes the antisense promoter for the miRNA that becomes the substrate for siRNA production.
Inhibition of the RNAi silencing mechanism in this region showed an increase in LINE1 transcription.
Evolution
Transposable elements are found in almost all forms of life, and the scientific community is still exploring their evolution and their effect on the evolution of the genome.
It is unclear whether transposable elements originated in the last universal common ancestor, arose independently multiple times, or arose once and then spread to other kingdoms via horizontal gene transfer.
While some transposable elements benefit their hosts, most are regarded as selfish DNA parasites.
In this way, they are similar to viruses. Several viruses and transposable elements also share characteristics in their genomic structures and biochemical capabilities, leading to speculation that they share a common ancestor.
Because the excessive activity of the transposable element can damage exons, many organisms have acquired mechanisms to inhibit their activity.
Bacteria can undergo high rates of gene deletion as part of a mechanism to remove transposable elements and viruses from their genomes. In contrast, eukaryotic organisms often use RNA interference to inhibit the activity of transposable elements.
However, some transposable elements generate large families often associated with speciation events. Evolution often deactivates DNA transposons, leaving them as introns (inactive gene sequences).
Invertebrate animal cells, almost all 100,000+ DNA transposons per genome have genes encoding inactive transposase polypeptides. In humans, all Tc1-like transposons are inactive.
The first synthetic transposon designed for use in vertebrate cells, the Sleeping Beauty transposon system, is a Tc1 / mariner type transposon. It exists in the human genome as an intron and was activated through reconstruction.
However, large amounts of transposable elements within genomes may still present evolutionary advantages. The interspersed repeats within genomes are created by transposition events that accumulate over evolutionary time.
Because interleaved repeats block gene conversion, they protect new gene sequences from overwriting similar gene sequences and thereby facilitate the development of new genes.
The vertebrate immune system may have also co-opted the transposable elements to produce a variety of antibodies. The V (D) J recombination system operates by a mechanism similar to some transposable elements.
The transposable elements can contain many types of genes, including those that confer antibiotic resistance and the ability to transpose to conjugative plasmids. Some transposable elements also contain integrons, genetic elements that can capture and express genes from other sources.
These contain integrase, which can integrate gene cassettes. There are more than 40 antibiotic resistance genes identified on cassettes and virulence genes.
Transposons do not always cut their elements precisely; sometimes, they remove adjacent base pairs; This phenomenon is called shuffling exon. Mixing two unrelated exons can create a new gene product or, more likely, an intron.
Applications
The first transposable element was discovered in corn (Zea mays) called the dissociator (Ds). Similarly, the first transposable element isolated molecularly was from a plant (dragon).
Appropriately, transposable elements have been a handy tool in plant molecular biology. Researchers use them as a means of mutagenesis. A transposable element jumps to a gene and produces a mutation in this context.
The presence of such a transposable element provides a direct means of identifying the mutant allele concerning chemical mutagenesis methods.
Sometimes the insertion of a transposable element into a gene can reversibly alter the function of that gene, in a process called insertional mutagenesis; Transposase-mediated cleavage of the DNA 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 within a cell to function (autonomous cell) and genes that produce observable effects in cells other than those in which the gene is expressed.
Transposable elements are also widely used for mutagenesis of most experimentally treatable organisms.
The Sleeping Beauty transposon system has been widely used as an insert tag to identify cancer genes.
The Tc1 / mariner class of transposable elements The Sleeping Beauty transposon system, awarded Molecule of the Year in 2009, is active in mammalian cells and is being investigated for use in human gene therapy.
Transposable elements are used to reconstruct phylogenies using presence/absence analysis.
De novo repeat identification
The de novo repeat identification is an initial scan of sequence data that seeks to find the repeating regions of the genome and classify these repeats.
There are many computer programs for de novo re-identification, all operating under the same general principles.
As short tandem repeats are generally 1-6 base pairs in length and are often consecutive, their identification is relatively simple.
On the other hand, Sparse repeating elements are more challenging to identify because they are longer and have often acquired mutations.
However, it is essential to identify these repeats as they are often found as transposable elements (TEs).
The de novo identification of transposons involves three steps:
- Find all the repeats within the genome.
- Build a consensus for each sequence family.
- Classify these repetitions.
There are three groups of algorithms for the first step. One cluster is the k-mer approach, where a Khmer is a sequence of length k.
In this approach, the genome is scanned for overrepresented k-mers; that is, k-mers occur more often than likely based on probability alone.
The length k is determined by the type of transposon being searched for. The k-mer approach also allows mismatches, the number determined by the analyst.
Some Khmer approximation programs use k-mer as a base and extend both ends of each repeated k-mer until there is no similarity between them, indicating the ends of the repeats.
Another group of algorithms employs a method called sequence autocompassing. Sequence self-comparison programs use databases such as AB-BLAST to perform initial sequence alignment.
Because these programs find clusters of elements that partially overlap, they help find highly divergent transposons or transposons with only a tiny region copied in other parts of the genome.
Another group of algorithms follows the periodicity approach.
These algorithms perform a Fourier transformation on the sequence data, identifying periodicities and regions that repeat periodically, and can use peaks in the resulting spectrum to find repeating candidate elements.
This method works best for tandem reps but can also be used for sparse reps. However, it is a slow process, making it an unlikely option for genome-wide analysis.
The second de novo repeat identification step involves building a consensus on each family of sequences. A consensus sequence is a sequence that is created based on repeats that comprise a family of transposable elements.
A consensus base pair is the one that occurs most frequently in the sequences being compared to reach a consensus.
For example, in a family of 50 repeats where 42 have a T base pair in the same position, the consensus sequence would also have a T.
Since the base pair represents the family as a whole in that particular position and is probably the base pair found in the family’s ancestor in that position.
Once a consensus sequence has been made for each family, it is possible to proceed to further analysis, such as sorting transposable elements and genome masking to quantify the overall content of the transposable element of the genome.
Adaptable transposable elements
Transposable elements have been recognized as good candidates to stimulate genetic adaptation through their ability to regulate the expression levels of nearby genes.
Combined with their “mobility,” transposable elements can relocate adjacent to their specific genes and control gene expression levels, depending on the circumstances.
The 2008 study, “High rate of adaptation induced by recent transfusible elements in Drosophila melanogaster,” used D. melanogaster, which had recently migrated from Africa to other parts of the world, as a basis for studying adaptations caused by transposable elements.
Although most of the transposable elements were located in introns, the experiment showed a significant difference in gene expressions between the population of Africa and other parts of the world.
The four transposable elements that caused the selective sweep were most prevalent in D. melanogaster from temperate climates, leading the researchers to conclude that the selective pressures of the climate were conducive to genetic adaptation.
From this experiment, transposable adaptive elements have been confirmed to be prevalent, allowing organisms to adapt gene expression due to new selective pressures.
However, not all the effects of transposable adaptive elements are beneficial to the population.
In 2009 research, “A recent adaptive insertion of the tradable element near highly conserved developmental loci in Drosophila melanogaster,” a transposable element inserted between Jheh 2 and Jheh 3, revealed a degradation in the expression level of both genes.
Downregulation of such genes has caused Drosophila to show an extended developmental time and reduced viability from egg to adult.
Although this adaptation was observed with high frequency in all non-African populations, it was not corrected.
This is not hard to believe. Logically, a population favors greater viability from egg to adult; therefore, it tries to purge the trait caused by this specific adaptation of transposable elements.
At the same time, there have been several reports showing the advantageous adaptation caused by transposable elements.
In the research carried out with silkworms, “An adaptive insertion of the transposable element in the regulatory region of the EO gene in the domesticated silkworm,” insertion of a transposable element was observed in the cis-regulatory region of the EO gene, which regulates the mute hormone 20E, and the enhanced expression was recorded.
While populations without the transposable element insert are often unable to effectively regulate hormone 20E under starvation conditions, those with the insert have a more stable development, resulting in more excellent uniformity of development.
These three experiments all demonstrated different ways in which insertions of transposable elements can be advantageous or disadvantageous by regulating the level of expression of adjacent genes.
