DNA transposon
DNA transposons are DNA sequences, sometimes referred to "jumping genes", that can move and integrate to different locations within the genome. They are class II transposable elements that move through a DNA intermediate, as opposed to class I TEs, retrotransposons, that move through an RNA intermediate. DNA transposons can move in the DNA of an organism via a single-or double-stranded DNA intermediate. DNA transposons have been found in both prokaryotic and eukaryotic organisms. They can make up a significant portion of an organism's genome, particularly in eukaryotes. In prokaryotes, TE's can facilitate the Horizontal [gene transfer|horizontal transfer] of antibiotic resistance or other genes associated with virulence. After replicating and propagating in a host, all transposon copies become inactivated and are lost unless the transposon passes to a genome by starting a new life cycle with horizontal transfer. DNA transposons do not randomly insert themselves into the genome, but rather show preference for specific sites.
With regard to movement, DNA transposons can be categorized as autonomous and nonautonomous. Autonomous ones can move on their own, while nonautonomous ones require the presence of another transposable element's gene, transposase, to move. There are three main classifications for movement for DNA transposons: "cut and paste," "rolling circle", and "self-synthesizing". These distinct mechanisms of movement allow them to move around the genome of an organism. Since DNA transposons cannot synthesize DNA, they replicate using the host replication machinery. These three main classes are then further broken down into 23 different superfamilies characterized by their structure, sequence, and mechanism of action.
DNA transposons are a cause of gene expression alterations. As newly inserted DNA into active coding sequences, they can disrupt normal protein functions and cause mutations. Class II TEs make up about 3% of the human genome. Today, there are no active DNA transposons in the human genome. Therefore, the elements found in the human genome are called fossils.
Mechanisms of action
Cut and paste
Traditionally, DNA transposons move around in the genome by a cut and paste method. The system requires a transposase enzyme that catalyzes the movement of the DNA from its current location in the genome and inserts it in a new location. Transposition requires three DNA sites on the transposon: two at each end of the transposon called terminal inverted repeats and one at the target site. The transposase will bind to the terminal inverted repeats of the transposon and mediate synapsis of the transposon ends. The transposase enzyme then disconnects the element from the flanking DNA of the original donor site and mediates the joining reaction that links the transposon to the new insertion site. The addition of the new DNA into the target site causes short gaps on either side of the inserted segment. Host systems repair these gaps resulting in the target sequence duplication that are characteristic of transposition. In many reactions, the transposon is completely excised from the donor site in what is called a "cut and paste" transposition and inserted into the target DNA to form a simple insertion. Occasionally, genetic material not originally in the transposable element gets copied and moved as well.Helitrons
Helitrons are also a group of eukaryotic class II TEs. Helitrons do not follow the classical "cut and paste" mechanism. Instead, they are hypothesized to move around the genome via a rolling circle like mechanism. This process involves making a nick to a circular strand by an enzyme, which separates the DNA into two single strands. The initiation protein then remains attached to the 5' Phosphate on the nicked strand, exposing the 3' hydroxyl of the complementary strand. This allows a polymerase enzyme to begin replication on the un-nicked strand. Eventually the entire strand is replicated at which point the newly synthesized DNA disassociates and is replicated in parallel with the original template strand. Helitrons encode an unknown protein which is thought to have HUH endonuclease function as well as 5' to 3' helicase activity. This enzyme would make a single stranded cut in the DNA which explains the lack of Target Site Duplications found in Helitrons. Helitrons were also the first class of transposable elements to be discovered computationally and marked a paradigm shift in the way that whole genomes were studied.Polintons
Polintons are also a group of eukaryotic class II TEs. As one of the most complex known DNA transposons in eukaryotes, they make up the genomes of protists, fungi, and animals, such as the entamoeba, soybean rust, and chicken, respectively. They contain genes with homology to viral proteins and which are often found in eukaryotic genomes, like polymerase and retroviral integrase. However, there is no known protein functionally similarly to the viral capsid or envelope proteins. They share their many structural characteristics with linear plasmids, bacteriophages and adenoviruses, which replicate using protein-primed DNA polymerases. Polintons have been proposed to go through a similar self-synthesis by their polymerase. Polintons, 15–20 kb long, encode up to 10 individual proteins. For replication, they utilize a protein-primed DNA polymerase B, retroviral integrase, cysteine protease, and ATPase. First, during host genome replication, a single-stranded extra-chromosomal Polinton element is excised from the host DNA using the integrase, forming a racket-like structure. Second, the Polinton undergoes replication using the DNA polymerase B, with initiation started by a terminal protein, which may encoded in some linear plasmids. Once the double stranded Polinton is generated, the integrase serves to insert it into the host genome. Polintons exhibit high variability between difference species and may tightly regulated, resulting in a low frequency rate in many genomes.Classification
As of the most recent update in 2023, 31 superfamilies of DNA transposons were recognized and annotated inRepbase, a database of repetitive DNA elements maintained by the Genetic Information Research Institute:
Effects of transposons
DNA transposons, like all transposons, are quite impactful with respect to gene expression. A sequence of DNA may insert itself into a previously functional gene and create a mutation. This can happen in three distinct ways: 1. alteration of function, 2. chromosomal rearrangement, and 3. a source of novel genetic material. Since DNA transposons may happen to take parts of genomic sequences with them, exon shuffling may occur. Exon shuffling is the creation of novel gene products due to the new placement of two previously unrelated exons through transposition. Because of their ability to alter DNA expression, transposons have become an important target of research in genetic engineering.Examples
Maize
Barbara McClintock first discovered and described DNA transposons in Zea mays, during the 1940s; this is an achievement that would earn her the Nobel Prize in 1983. She described the Ac/Ds system where the Ac unit was autonomous but the Ds genomic unit required the presence of the activator in order to move. This TE is one of the most visually obvious as it was able to cause the maize to change color from yellow to brown/spotted on individual kernels.Fruit flies
The Mariner/Tc1 transposon, found in many animals but studied in Drosophila was first described by Jacobson and Hartl. Mariner is well known for being able to excise and insert horizontally in to a new organism. Thousands of copies of the TE have been found interspersed in the human genome as well as other animals.The Hobo transposons in Drosophila have been extensively studied due to their ability to cause gonadal dysgenesis. The insertion and subsequent expression of hobo-like sequences results in the loss of germ cells in the gonads of developing flies.