Transposable element


A transposable element, also transposon, or jumping gene, mobile genetic element, is a nucleic acid sequence in DNA that can change its position within a genome, an observation first made via careful genetic studies in corn, by Barbara McClintock.
TEs are very common in all types of organisms in nature, including in plants and animals. As of 2008, there were at least two classes of TEs: Class I TEs or retrotransposons, which generally function via reverse transcription; and Class II TEs or DNA transposons, which encode the protein transposase, which they require for insertion, excision, or other TE functions.

Discovery

While eventually being understood to apply broadly in biology, the discovery of TEs by Barbara McClintock came many decades before this broadening, during her early studies at the Cold Spring Harbor Laboratory in New York, that identified them in maize. At CSH, McClintock had been experimenting with plants that had presented evidence of having breaks in their chromosomes.
In the winter of 1944–1945, McClintock planted corn kernels that were self-pollinated, meaning that the silk of the flower received pollen from its own anther. These kernels came from a long line of plants that had been self-pollinated, causing broken arms on the end of their ninth chromosomes. As the plants began to grow, McClintock noted unusual color patterns on the leaves; for example, one leaf had two albino patches of almost identical size, located side by side on the leaf. McClintock hypothesized that during cell division certain cells lost genetic material, while others gained what they had lost. However, when comparing the chromosomes of the current generation of plants with the parent generation, she found certain parts of the chromosome had switched position. This refuted the popular genetic theory of the time that genes were fixed in their position on a chromosome. McClintock found that genes could not only move but they could also be turned on or off due to certain environmental conditions or during different stages of cell development. She also showed that these gene mutations could be reversed.
McClintock reported her findings in 1951, and published them in the journal, Genetics, in November 1953, in an article titled "Induction of Instability at Selected Loci in". At the 1951 Cold Spring Harbor Symposium, where she first publicized her findings, her talk was met with silence. Her work was largely dismissed and ignored until the late 1960s–1970s when, after TEs were found in bacteria, after which, their presence in eukaryotes was rediscovered.
McClintock was awarded a Nobel Prize in Physiology or Medicine in 1983 for her discovery of TEs, more than thirty years after her initial research.

Classification

Transposable elements represent one of several types of mobile genetic elements. TEs are assigned to one of two classes according to their mechanism of transposition, which can be described as either copy and paste or cut and paste.

Class I: Retrotransposons

Class I TEs are copied in two stages: first, they are transcribed from DNA to RNA, and the RNA produced is then reverse transcribed to DNA. This copied DNA is then inserted back into the genome at a new position. The reverse transcription step is catalyzed by a reverse transcriptase, which is often encoded by the TE itself. The characteristics of retrotransposons are similar to retroviruses, such as HIV.
Despite the potential negative effects of retrotransposons, like inserting itself into the middle of a necessary DNA sequence, which can render important genes unusable, they are still essential to keep a species' ribosomal DNA intact over the generations, preventing infertility. The R2 retrotransposon of Drosophila creates double-stranded breaks by endonuclease activity during its process of replication within its target rDNA, allowing for homologous recombination between sister chromatids to repair the breaks. The resulting chromatids, each with different quantities of rDNA, are tagged and differentially segregated during asymmetric division of progenitors into daughter stem cells, which receive the chromatids with more rDNA, and germ cell precursors.
As of this date, Retrotransposons are commonly grouped into three main categories:
Retroviruses can also be considered TEs. After conversion of retroviral RNA into DNA inside a host cell, the newly produced retroviral DNA is integrated into the genome of the host cell, integrated DNA segments termed proviruses. The provirus is a specialized form of eukaryotic retrotransposon, which can produce RNA intermediates that may leave the host cell and infect other cells. The transposition cycle of retroviruses has similarities to that of prokaryotic TEs, suggesting a distant relationship between the two.

Class II: DNA transposons

The cut-and-paste transposition mechanism of class II TEs does not involve an RNA intermediate. The transpositions are catalyzed by several transposase enzymes. Some transposases non-specifically bind to any target site in DNA, whereas others bind to specific target sequences. The transposase makes a staggered cut at the target site producing sticky ends, cuts out the DNA transposon and ligates it into the target site. A DNA polymerase fills in the resulting gaps from the sticky ends and DNA ligase closes the sugar-phosphate backbone. This results in target site duplication and the insertion sites of DNA transposons may be identified by short direct repeats followed by inverted repeats.
Cut-and-paste TEs may be duplicated if their transposition takes place during S phase of the cell cycle, when a donor site has already been replicated but a target site has not yet been replicated. Such duplications at the target site can result in gene duplication, which plays an important role in genomic evolution.
Not all DNA transposons transpose through the cut-and-paste mechanism. In some cases, a replicative transposition is observed in which a transposon replicates itself to a new target site.
Class II TEs comprise less than 2% of the human genome, making the other tranposons Class I.

Autonomous and non-autonomous

Transposition can be classified as either "autonomous" or "non-autonomous" in both Class I and Class II TEs. Autonomous TEs can move by themselves, whereas non-autonomous TEs require the presence of another TE to move. This is often because dependent TEs lack transposase or reverse transcriptase.
Activator element is an example of an autonomous TE, and dissociation elements is an example of a non-autonomous TE. Without Ac, ''Ds'' is not able to transpose.

Class III transposons

Some researchers also identify a third class of transposable elements, which has been described as "a grab-bag consisting of transposons that don't clearly fit into the other two categories". Examples of such TEs are the Foldback elements of Drosophila melanogaster, the TU elements of Strongylocentrotus purpuratus, and Miniature Inverted-repeat Transposable Elements.

Genomic locations

Transposable elements can be all over a genome, and in the case of maize, TEs make up 50% of the genome. In yeast, over 90% of the Ty1 through T4 elements are located within 750 bp upstream of genes transcribed by RNA polymerase III, particularly tRNA genes. The Ty5 elements are all located at the telomeres or regions with telomeric chromatin.

Diseases and other negative effects

Transposable elements can damage the genome of their host cell in different ways:
  • A TE can insert into a functional gene and disable that gene.
  • After a DNA TE is excised, the resulting gap may not be repaired correctly.
  • Many TEs contain promoters that drive transcription of their own genes, and thus cause aberrant expression of linked genes.
As of 2006, diseases asssociated with TEs included:
  • Hemophilia A and B. LINE1 TEs that insert into the human Factor VIII gene have been shown to result in haemophilia.
  • Severe combined immunodeficiency. Insertion of L1 into the APC gene has been associated with a case of colon cancer.
  • Porphyria. Insertion of Alu element into the PBGD gene leads to interference with the coding region and to acute intermittent porphyria.
  • Predisposition to cancer. LINE1 TE's and other retrotransposons have been linked to cancer, as a result of their association with genomic instability.
  • Muscular dystrophies. Fukuyama congenital muscular dystrophy is thought to be caused by a mutation derived from an SVA transposable element insertion in the fukutin gene in the ancestral founder, which rendered the gene inactive.
  • Alzheimer's and other tauopathies. Transposable element dysregulation can cause neuronal death, which has been associated with this type of neurodegenerative disorder.

    Evolution

TEs are found in almost all 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. Because excessive TE activity can damage exons, many organisms have acquired 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. Nevertheless, some TEs generate large families often associated with speciation events. Evolution often deactivates DNA transposons, leaving them as introns. In vertebrate animal cells, nearly all 100,000+ DNA transposons per genome have genes that encode inactive transposase polypeptides.