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05.23.04 (4 years ago)
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Transposons are sequences of DNA that can move around to different positions within the genome of a single cell. In the process, they can cause mutations, and change the amount of DNA in the genome. Transposons are also called "jumping genes" or "transposable genetic elements". Transposons can move directly from one position to another within the genome, while retroposons have first to be transcribed to RNA and then back to DNA by reverse transcriptase. Transposons are very useful to researchers as a means to alter DNA inside of a living organism.
Mechanism
A transposon needs the enzyme transposase, which is often encoded by the transposon itself. The ends of the transposon sequence consist of inverted repeats (identical sequences reading in opposite directions). The transposase binds to both the inverted repeats of the transposon and the target site on the genome, where the transposon will move to. This target site is cut, leaving sticky ends. The transposon is then ligated into the target site, the gaps are filled in, resulting in direct repeats.
Examples
The first transposons were discovered in maize (zea mays, aka corn) by Barbara McClintock in 1940, for which she was awarded a Nobel Prize in 1983. She noticed insertions, deletions and translocations, caused by these transposons. These changes in the genome could, for example, lead to a change in color. About 50% of the total genome of maize consists of transposons.
Transposons in Drosophila (the fruit fly) are called P elements. They seem to have first appeared in Drosophila melanogaster only about 50 years ago. Since then, they have spread through every population of the species. Artificial P elements can be used to insert genes into Drosophila by injecting the embryo.
Transposons in bacteria usually carry an additional gene for a function other than transposase, often an antibiotic resistance. In bacteria, transposons can jump from the "regular" DNA to plasmids and back, allowing the transfer and permanent addition of, for example, antibiotic resistance, leading to multiresistant strains.
Transposons causing diseases
Transposons are mutagens. They can damage the genome of their host cell in different ways :
A transposon/retroposon that inserts itself into a functional gene will most likely disable that gene.
After a transposon left a gene, the resulting gap can probably not be repaired correctly.
Multiple copies of the same sequence (e.g., Alu) can hinder precise chromosomal pairing during mitosis, resulting in unequal crossovers, one of the main reasons for chromosome duplication.
Diseases that are often caused by transposons include Hemophilia A and B, SCID, porphyria, predisposition to cancer, and Duchenne muscular dystrophy.
Evolution of transposons
The evolution of transposons and their effect on genome evolution is currently a dynamic field of study.
Since transposons are found in all major branches of life, they must have either existed in the last universal common ancestor or have arisen independently multiple times. While transposons may confer some benefits on their hosts, they are generally considered to be selfish DNA, parasites that live within the genome of cellular organisms. In this way, they are similar to viruses. Viruses and transposons also share features in their genome structure and biochemical abilities, leading to speculation that they share a common ancestor.
Since excessive transposon activity can destroy a genome, many organisms seem to have developed mechanisms to reduce transposition to a manageable level. Bacteria may undergo high rates of gene deletion as part of a mechanism to remove transposons and viruses from their genomes while eukaryotic organisms may have developed the RNA interference (RNAi) mechanism as a way of reducing transposon activity.
In the flatworm C. elegans, some genes required for RNAi also reduce transposon activity.
Transposons may have been co-opted by the vertebrate immune system as a means of producing antibody diversity. The V(D)J recombination system operates by a mechanism of similar to that of transposons.
Transposons in science
Transposons were first discovered in plants. Likewise, the first transposon to be molecularly isolated was from a plant (Snapdragon). Appropriately, transposons have been an especially useful tool in plant molecular biology. Researchers use transposons as a means of mutagenesis. In this context, a transposon jumps into a gene and produces an interesting mutation. The presence of the transposon provides a straightforward means of identifying the locus that has been mutated, relative to chemical mutagenesis methods. Sometimes the insertion of a transposon into a gene can disrupt that gene's function in a reversible manner; transposase mediated excision of the 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.
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