Transposon

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 genome size. Transposition often results in duplication of the TE. Barbara McClintock's discovery of these jumping genes earned her a Nobel Prize in 1983.

Transposable elements make up a large fraction of the genome and are responsible for much of the mass of DNA in a eukaryotic cell. It has been shown that TEs are important in genome function and evolution. In Oxytricha, which has a unique genetic system, these elements play a critical role in development. Transposons are also very useful to researchers as a means to alter DNA inside a living organism.

There are at least two classes of TEs: Class I TEs or retrotransposons generally function via reverse transcription, while Class II TEs or DNA transposons encode the protein transposase, which they require for insertion and excision, and some of these TEs also encode other proteins.

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.

Retrotransposons are commonly grouped into three main orders:

·         TEs with long terminal repeats (LTRs), which encode reverse transcriptase, similar to retroviruses

·         Long interspersed nuclear elements (LINEs, LINE-1s, or L1s), which encode reverse transcriptase but lack LTRs, and are transcribed by RNA polymerase II

·         Short interspersed nuclear elements do not encode reverse transcriptase and are transcribed by RNA polymerase III

[Note: Retroviruses can also be considered TEs. For example, 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. These integrated DNAs are 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 (a staggered cut in the target DNA filled by DNA polymerase) followed by inverted repeats (which are important for the TE excision by transposase).

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 (e.g. helitron).

Class II TEs comprise less than 2% of the human genome, making the rest Class I

Applications-

The first TE was discovered in maize (Zea mays) and is named dissociator (Ds). Likewise, the first TE to be molecularly isolated was from a plant (snapdragon). Appropriately, TEs have been an especially useful tool in plant molecular biology. Researchers use them as a means of mutagenesis. In this context, a TE jumps into a gene and produces a mutation. The presence of such a TE provides a straightforward means of identifying the mutant allele relative to chemical mutagenesis methods.

Sometimes the insertion of a TE into a gene can disrupt that gene's function in a reversible manner, in a process called insertional mutagenesis; transposase-mediated excision 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 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.

TEs are also a widely used tool for mutagenesis of most experimentally tractable organisms. The Sleeping Beauty transposon system has been used extensively as an insertional tag for identifying cancer genes.

The Tc1/mariner-class of TEs 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.

TEs are used for the reconstruction of phylogenies by the means of presence/absence analyses.