Transposons: Mobile DNA

Transposons are segments of DNA that can move around to different positions in the genome of a single cell. In the process, they may

These mobile segments of DNA are sometimes called "jumping genes".

There are two distinct types:

Class II Transposons

Class II transposons move by a "cut and paste" process: the transposon is cut out of its location (like command/control-X on your computer) and inserted into a new location (command/control-V).

This process requires an enzyme — a transposase — that is encoded within some of these transposons.

Transposase binds to:

The DNA at the target site is cut in an offset manner (like the "sticky ends" produced by some restriction enzymes [Examples]).

After the transposon is ligated to the host DNA, the gaps are filled in by Watson-Crick base pairing. This creates identical direct repeats at each end of the transposon.

Often transposons lose their gene for transposase. But as long as somewhere in the cell there is a transposon that can synthesize the enzyme, their inverted repeats are recognized and they, too, can be moved to a new location.

Miniature Inverted-repeat Transposable Elements (MITEs)

The recent completion of the genome sequence of rice and C. elegans has revealed that their genomes contain thousands of copies of a recurring motif consisting of MITEs are too small to encode any protein. Just how they are copied and moved to new locations is still uncertain. Probably larger transposons that are responsible.

There are over 100,000 MITEs in the rice genome (representing some 6% of the total genome). Some of the mutations found in certain strains of rice are caused by the insertion of a MITE in the gene.

MITEs have also been found in the genomes of humans, Xenopus, and apples.

Transposons in maize

The first transposons were discovered in the 1940s by Barbara McClintock who worked with maize (Zea mays, called "corn" in the U.S.). She found that they were responsible for a variety of types of gene mutations, usually
Some of the mutations (c, bz) used as examples of how gene loci are mapped on the chromosome were caused by transposons. [Link]

In developing somatic tissues like corn kernels, a mutation (e.g., c) that alters color will be passed on to all the descendant cells. This produces the variegated pattern which is so prized in "Indian corn". (Photo courtesy of Whalls Farms.)

It took about 40 years for other scientists to fully appreciate the significance of Barbara McClintock's discoveries. She was finally awarded a Nobel Prize in 1983.

Transposons in Drosophila

P elements are Class II transposons found in Drosophila. They do little harm because expression of their transposase gene is usually repressed. However, when male flies with P elements mate with female flies lacking them, the transposase becomes active in the germline producing so many mutations that their offspring are sterile.

In nature this is no longer a problem. P elements seem to have first appeared in Drosophila melanogaster about 50 years ago. Since then, they have spread through every population of the species. Today flies lacking P elements can only be found in old strains maintained in the laboratory.

P elements have provided valuable tools for Drosophila geneticists. Transgenic flies containing any desired gene can be produced by injecting the early embryo with an engineered P element containing that gene.

Other transposons are being studied for their ability to create transgenic insects of agricultural and public health importance.

Transposons in bacteria

Some transposons in bacteria carry — in addition to the gene for transposase — genes for one or more (usually more) proteins imparting resistance to antibiotics. When such a transposon is incorporated in a plasmid, it can leave the host cell and move to another. This is the way that the alarming phenomenon of multidrug antibiotic resistance spreads so rapidly.

Transposition in these cases occurs by a "copy and paste" (command/control-C -> command/control-V) mechanism. This requires an additional enzyme — a resolvase — that is also encoded in the transposon itself. The original transposon remains at the original site while its copy is inserted at a new site.

Retrotransposons

Retrotransposons also move by a "copy and paste" mechanism but in contrast to the transposons described above, the copy is made of RNA, not DNA.

The RNA copies are then transcribed back into DNA — using a reverse transcriptase — and these are inserted into new locations in the genome.

Many retrotransposons have long terminal repeats (LTRs) at their ends that may contain over 1000 base pairs in each.

Like DNA transposons, retrotransposons generate direct repeats at their new sites of insertion. In fact, it is the presence of these direct repeats that often is the clue that the intervening stretch of DNA arrived there by retrotransposition.

Some 50% of the entire human genome consists of retrotransposons.

LINEs (Long interspersed elements)

Through this copy-paste mechanism, the number of LINEs can increase in the genome.

The diversity of LINEs between individual human genomes make them useful markers for DNA "fingerprinting".

Variation occurs in the length of L1 elements:

While L1 elements are not functional, they may play a role in regulating the efficiency of transcription of the gene in which they reside (see below).

Occasionally, L1 activity makes and inserts a copy of a cellular mRNA (thus a natural cDNA). Lacking introns as well as the necessary control elements like promoters, these genes are not expressed. They represent one category of pseudogene.

SINEs (Short interspersed elements)

SINEs are short DNA sequences (100–400 base pairs) that represent reverse-transcribed RNA molecules originally transcribed by RNA polymerase III; that is, molecules of tRNA, 5S rRNA, and some other small nuclear RNAs.

The most abundant SINEs are the Alu elements. There are over one million copies in the human genome (representing 9% of our total DNA).

Alu elements consist of a sequence averaging 260 base pairs that contains a site that is recognized by the restriction enzyme AluI. They appear to be reverse transcripts of 7S RNA, part of the signal recognition particle.

Most SINEs do not encode any functional molecules and depend on the machinery of active L1 elements to be transposed; that is, copied and pasted in new locations.

HIV-1

HIV-1 — the cause of AIDS — and other human retroviruses (e.g., HTLV-1, the human T-cell leukemia/lymphoma virus) behave like retrotransposons.

The RNA genome of HIV-1 contains a gene for

Molecules of both enzymes are incorporated in the virus particle.
Link to an illustration and further discussion.

Transposons and Mutations

Transposons are mutagens. They can cause mutations in several ways: SINEs (mostly Alu sequences) and LINEs cause only a small percentage of human mutations. (There may even be a mechanism by which they avoid inserting themselves into functional genes.) However, they have been found to be the cause of the mutations responsible for some cases of human genetic diseases, including:

What good are transposons?

Transposons have been called "junk" DNA and "selfish" DNA.

Because of the sequence similarities of all the LINEs and SINEs, they also make up a large portion of the "repetitive DNA" of the cell.

Retrotransposons cannot be so selfish that they reduce the survival of their host. And it now appears that many, at least, confer some benefit. The ENCODE project found that some 75% of our repetitive DNA occurs within, or overlaps with, sequences, like enhancers, that regulate gene expression.

Some other possibilities:

Transposons and the C-value Paradox

So it seems likely that the lack of an association between size of genome and number of functional genes — the C-value paradox — is caused by the amount of transposon DNA accumulated in the genome.

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20 September 2012