Mobile DNA

Mobile DNA is a general term referring to blocks of DNA that is able to move and insert into new locations throughout the genome without needing DNA sequence similarity or using the process of homologous recombination.

Such process of movement and insertion is often called transposition, and the mobile DNAs are frequently called transposons. Some mobile DNAs ("DNA elements") move by different mechanisms than used strictly defined transposons, but achieve the same general outcome - namely movement of blocks of DNA to new positions in chromosomes.

Transposition

Transposition is a process where sections of DNA move throughout the genome, often making copies of themselves at the same time. Not all DNA does this, only sections called transposons, transposable elements, or jumping genes. Transposons have been called junk DNA, because they have no known useful function, and selfish DNA because they exploit the genetic mechanisms of the cell. However, this ability has conferred upon pathogenic bacteria the disturbing advantage of acquiring resistance to a number of antibiotics, and then transmitting this multiple drug resistance in a highly infectious way.

The mechanism of transposons

Transposons usually code for at least one gene, as they need the enzyme transposase, and the transposon usually codes for this itself. The ends of the transposon consist of terminal repeats which the transposase binds to. The transposase also binds to the target site on the genome, which is cut to leave "sticky ends', or single stranded DNA overhangs similar to those created by restricion endonucleasess. Depending on the type of transposon it is then either copied or cut out and inserted into the target site by the action of the enzyme DNA ligase .

Some transposons encode mechanisms for copying themselves, but many more exploit the cell's own DNA copying mechanism

For more on the mechanisms see Types of transposon.

Types of transposon

There are three different types of transposon, classified by their mechanisms:

Class I: Retrotransposons

Retrotransposons (sometimes Retroposons) work by copying themselves and pasting copies back into the genome, in multiple places. First retrotransposons copy themselves to RNA (transcription), but instead of being translated the RNA is picked up by reverse transcriptase (often coded by the transposon itself) which copies the RNA back into DNA which is then inserted into the genome. Retrotransposons usually have very long terminal repeats of over 1000 base pairs, making them easy to find and study.

Retrotransposons behave very similarly to retroviruses, such as HIV, giving a clue to their evolutionary origins (see #The evolution of transposons).

Class II transposons

Class II transposons move by cut and paste, rather than copy and paste, using the transposase enzyme. Different types of transposase work in different ways. Some can bind to any part of the DNA molecule, and the target site can therefore be anywhere, while others bind to specific sequences. The transposase then cuts the target site to produce sticky ends, cuts out the transposon and ligases it into the target site, and then fills in the sticky ends with their base pairs.

Transposons may lose their ability to synthesise transposase through mutation, yet continue to jump through the genome because other transposons are still producing transposase. It is possible that some transposons become transposons simply by mutations producing the sequences that signals to transposase.

P elements

P elements are a particular type of class II transposon that was first detected in Drosophila (fruit flies) in the 1950s. P elements are so good at spreading that they cause so many mutations in the germ line cells as to sterilise the flies. Drosophila have evolved a mechanism for supressing transposase, however, and all except a few isolated lab populations are immune to the effects of P elements. The roundworm Caenorhabditis elegans has evolved an RNA interference system to respond to a similar problem of transposons.

Class III: Miniature Inverted-repeat Transposable Elements

MITEs are sequences of about 400 base pairs and 15 base pair inverted repeats that vary very little. They are found in their thousands in the genomes of both plants and animals (over 100,000 were found in the rice genome). MITEs are too small to encode any proteins.

Effects of transposons on the genome

Transposons can cause mutation. They do this either by being inserted into the coding region of a gene, losing some of the gene in the process, or by being inserted upstream of the coding region of a gene in an area important in determining the expression of the gene, such an area where a transcription factor would bind to the DNA. Insertion into a gene can also cause alternative splicing leading to a greater diversity of proteins produced by a single gene.

Transposons have been linked to the creation of new "chimeric' (hybrid) proteins by gene fusion , and in generation of the circuitry of complex new gene regulatory networks.

An important illustration of this evolutionary role has been found in human evolution, involving a member of the mariner-family transposons called Hsmar1. Hsmar1 (Homo sapiens mariner) is present in the human genome as around 1500 copies of mobile DNA.

SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of Hsmar1 mobile DNA The transposase gene was recruited as part of SETMAR 40-58 million years ago in an anthropoid ape, after the insertion of an Hsmar1 transposon downstream of a preexisting SET gene.

Transposons can cause segments of DNA to be duplicated, an important first stage in the Evolution of new information.

Transposons also increase the size of the genome, because they leave multiple copies of themselves in the genome.

Transposons can play a part in causing diseases including cancer and haemophilias A (when the Factor VIII gene is disrupted) and B (Factor IX.

The evolution of transposons

The evolution of transposons is an area of much current research, and we can't yet say exactly how transposons came about. However, we do know that many similar transposons can be found in all major groups of organisms on earth. There are three pausible hypothesis as to how this came about:

• The transposons were there in the Last universal common ancestor
• The transposons have arisen a number of times independently (less likely when the transposons are so similar)
• The transposons can be spread in viruses

The hypothesis that transposons can be spread in viruses is supported by evidence in bacteria. In many bacteria transposons contain genes for antibiotic resistance, and when snipped out of the bacteria's circular DNA the plasmids produced can be transfered to other bacterial cells, spreading the resistance to other species by horizontal gene transfer.

In terms of gene selection, there is an obvious selectionary advantage for bits of DNA that do nothing but copy themselves and allow the rest of the genome to do all the hard work, from the point of view of that piece DNA. At first sight it would like like transposons are bad for the gemone as a whole, jumping around causing mutations and silencing of genes, and that organisms would evolve defences against these DNA parasites. It's possible, however, that transposons are actually selectively advantageous for the genome as a whole. The bulking out of the genome with transposons and other non-coding DNA could make gene regulation easier. Some retrotransposons and retroviruses have sequences similar to the exon, promoter and enhancer regions and DNA, and this may also play a part in gene regulation, or provide a good evolutionary substrate. Transposon activity is greater when the organism is under stress, and this could lead to increased mutation rates when an organism is in an environment it is not well adapted to. There is also evidence that genomes are more stable and better able to survive temperature stress the larger they are.

The discovery of transposons

Transposons were first discovered in maize in 1940 by Barbara McClintock, and were initially thought to be a feature only of Plants. McClintock noticed that the transposons caused insertion, deletion and translocation mutations. The discovery was initially greeted with widespread scepticism as geneticists could not make the discovery fit with the knowledge of genetics at that time. However, as more became known the significance of the discovery was recognised, and in 1983 McClintock was awarded the Nobel Price in Physiology or Medicine.

Some uses for transposons

Transposons can be exploited by scientists for studying genetics. Because transposons insert themselves into genes they can be used to knock out genes. This technique turns genes off so that their function can be determined.

Further reading

• Berg, D.E, and Howe, M. M. (Mobile DNA. American Society for Microbiology, Washington DC.1989)
• Transposon
• Dawkins, R., 1982. The Extended Phenotype. Oxford University Press.
• Kimball's biology pages: Transposons
• Russel, P.J., 2002. iGenetics. Benjamin Cummings.
• Jurka, J. Evolutionary impact of human Alu repetitive elements Curr. Opin. Genet. Dev. (2004) 14, 603–608. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15531153&query_hl=9

See also

The following are similar to transposons:

• Long interspersed element
• Pseudogene
• Retrovirus
• Short interspersed element

This page was originally derived December 5 2006 from Transposition, part of the EvoWiki encyclopedia of genetics and molecular biology. Further use is subject to the Creative Commons Licence conditions.