- Transposon
Transposons are sequences of
DNA that can move around to different positions within thegenome of a single cell, a process called transposition. In the process, they can causemutation s and change the amount of DNA in the genome. Transposons were also once called "jumping genes", and are examples ofmobile genetic elements . They were discovered byBarbara McClintock early in her career [cite journal
journal=Proc Natl Acad Sci U S A.
year=1950
month=Jun
volume=36
issue=6
pages=344–55
title=The origin and behavior of mutable loci in maize
last=McCLINTOCK
first=B.
pmid=15430309
doi=10.1073/pnas.36.6.344] , for which she was awarded aNobel prize in1983 .There are a variety of mobile genetic elements, and they can be grouped based on their mechanism of transposition. Class I mobile genetic elements, orretrotransposon s, move in the genome by being transcribed toRNA and then back to DNA byreverse transcriptase , while class II mobile genetic elements move directly from one position to another within the genome using atransposase to "cut and paste" them within the genome.Transposons are very useful to researchers as a means to alter DNA inside of a living organism. Transposons make up a large fraction ofgenome size s which is evident through theC-value s of eukaryotic species.Types of transpositions
Transposons are classified into two classes based on their mechanism of transposition.
Class I: Retrotranspositions
Retrotransposons work by copying themselves and pasting copies back into the genome in multiple places. Initially retrotransposons copy themselves to
RNA (transcription) but, in addition to being transcribed, the RNA is copied intoDNA by areverse transcriptase (often coded by the transposon itself) and inserted back into the genome.Retrotransposons behave very similarly to
retrovirus es, such asHIV , giving a clue to theevolution ary origins of such viruses.There are three main classes of retrotransposons:
*Viral: encode reverse transcriptase (to reverse transcribe RNA into DNA), have
long terminal repeat s (LTRs), similar to retroviruses
*LINEs: encode reverse transcriptase, lack LTRs, transcribed byRNA polymerase II
*Nonviral superfamily: do not code for reverse transcriptase, transcribed byRNA polymerase III Retroviruses as transposable elements
Retroviruses were first identified 80 years ago as agents involved in the onset of cancer. More recently the AIDS epidemic has been shown to be due to the HIV retrovirus. In the early 1970s it was discovered that retroviruses had the ability to replicate their RNA genomes via conversion into DNA which became stably integrated in the DNA of the host cell. It is only comparatively recently that retroviruses have been recognized as particularly specialized forms of eukaryotic transposons. In effect they are transposons which move via RNA intermediates that usually can leave the host cells and infect other cells. The integrated DNA form (provirus) of the retrovirus bears a marked similarity to a transposon.The transposition cycle of retroviruses has other similarities to prokaryotic transposons, which suggest a distant familial relationship between these two types of transposon. Crucial intermediates in retrovirus transposition are extrachromosomal DNA molecules. These are generated by copying the RNA of the virus particle into DNA by a retrovirus-encoded polymerase called
reverse transcriptase . The extra chromosomal linear DNA is the direct precursor of the integrated element and the insertion mechanism bears a strong similarity to "cut and paste" transposition.Class II: DNA transposons
The major difference of class II transposons from retrotransposons is that their transposition mechanism does not involve an RNA intermediate. Class II transposons usually move by a mechanism analogous to
cut and paste , rather thancopy and paste , using thetransposase 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. Transposase makes a staggered cut at the target site producingsticky ends , cuts out the transposon and ligates it into the target site. ADNA polymerase fills in the resulting gaps from the sticky ends andDNA 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 transposon excision by transposase).Not all DNA transposons transpose through cut and paste mechanism. In some cases a
replicative transposition is observed in which transposon replicates itself to a new target site.The transposons which only move by cut and paste may duplicate themselves if the transposition happens during
S phase of thecell cycle when the "donor" site has already been replicated, but the "target" site has not.Both classes of transposon may lose their ability to synthesise reverse transcriptase or transposase through mutation, yet continue to jump through the genome because other transposons are still producing the necessary enzyme.
Examples
* The first transposons were discovered in
maize ("Zea mays"), (corn species) byBarbara McClintock in1948 , for which she was awarded aNobel Prize in1983 . She noticed insertions, deletions, and translocations, caused by these transposons. These changes in the genome could, for example, lead to a change in the color of corn kernels. About 50% of the total genome of maize consists of transposons. The Ac/Ds system McClintock described are class II transposons.
* One family of transposons in the fruit fly "Drosophila melanogaster " are called "P element s". They seem to have first appeared in thespecies only in the middle of the twentieth century. Within 50 years, they have spread through everypopulation of the species.Gerald Rubin andAllan Spradling pioneered technology to use artificial P elements to insert genes into Drosophila by injecting theembryo . [Spradling AC, Rubin GM. Transposition of cloned P elements into Drosophila germ line chromosomes. Science. 1982 Oct 22;218(4570):341–347.] [Rubin, G.M., Spradling, A.C. (1982). Genetic transformation of Drosophila with transposable element vectors. Science 218(4570): 348-353.] [Francesca Cesari, [http://www.nature.com/milestones/miledna/full/miledna09.html "Milestones in Nature: Milestone 9: Transformers, Elements in Disguise"] , "Nature", Oct. 15, 2007.]
* Transposons in bacteria usually carry an additional gene for function other than transposition---often forantibiotic resistance . In bacteria, transposons can jump from chromosomal DNA toplasmid DNA and back, allowing for the transfer and permanent addition of genes such as those encoding antibiotic resistance (multi-antibiotic resistant bacterial strains can be generated in this way). Bacterial transposons of this type belong to the Tn family. When the transposable elements lack additional genes, they are known asinsertion sequence s.
* The most common form of transposon inhuman s is theAlu sequence . TheAlu sequence is approximately 300 bases long and can be found between 300,000 and a million times in the humangenome .
*Mu phage transposition is the best known example ofreplicative transposition . Its transposition mechanism is somewhat similar to ahomologous recombination .Transposons causing diseases
Transposons are
mutagen s. They can damage the genome of their host cell in different ways:
* A transposon or a retroposon that inserts itself into a functional gene will most likely disable that gene.
* After a transposon leaves a gene, the resulting gap will probably not be repaired correctly.
* Multiple copies of the same sequence, such asAlu sequence s can hinder precise chromosomal pairing duringmitosis andmeiosis , resulting in unequal crossovers, one of the main reasons for chromosome duplication.Diseases that are often caused by transposons include
hemophilia A and B,severe combined immunodeficiency ,porphyria , predisposition tocancer , andDuchenne muscular dystrophy .Additionally, many transposons contain promoters which drive transcription of their own
transposase . These promoters can cause aberrant expression of linked genes, causing disease ormutant phenotypes .Evolution of transposons
The evolution of transposons and their effect on genome evolution is currently a dynamic field of study.
Transposons are found in all major branches of life. They may or may not have originated in the
last universal common ancestor , or arisen independently multiple times, or perhaps arisen once and then spread to other kingdoms byhorizontal gene transfer [cite journal
journal=Genetica
year=1992
volume=86
issue=1
pages=275–286
title=Horizontal transfer of P elements and other short inverted repeat transposons
last=Kidwell
first=M.G.
doi=10.1007/BF00133726] . While transposons may confer some benefits on their hosts, they are generally considered to beselfish DNA parasite s that live within the genome of cellular organisms. In this way, they are similar tovirus es. 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 eukaryoticorganism s may have developed theRNA interference (RNAi) mechanism as a way of reducing transposon activity. In the nematode "Caenorhabditis 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 similar to that of transposons.Evidence exists that transposable elements may act as mutators in bacteria.
Applications
The first transposon was discovered in the plant
maize ("Zea mays", corn species), and is nameddissociator (Ds). 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 a mutation. The presence of the transposon provides a straightforward means of identifying the mutant allele, 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
genotype s. 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.Transposons are also a widely used tool for mutagenesis of most experimentally tractable organisms.
ee also
*
Insertion sequence
*Intragenomic conflict
*P element
*Tn10
*Signature tagged mutagenesis References
* cite book
author=Kidwell, M.G.
year=2005
chapter=Transposable elements.
title=The Evolution of the Genome
editor= (ed. T.R. Gregory)
pages=165-221
publisher=Elsevier
location=San Diego
isbn=0-12-301463-8
*cite book
author=Craig NL, Craigie R, Gellert M, and Lambowitz AM (ed.)
year=2002
title=Mobile DNA II
publisher=ASM Press
location=Washington, DC
isbn=978-1555812096
* cite book
author=Lewin B
year=2000
title=Genes VII
publisher=Oxford University Press.
isbn=978-0198792765Notes
External links
* [http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Transposons.html Kimball's Biology Pages: Transposons]
* [http://www.newscientist.com/article.ns?id=mg19025565.500&feedId=online-news_rss20 A possible connection between aberrant reinsertions and lymphoma] - New Scientist
* [http://www.gmo-safety.eu/en/gene_transfer/ Precision genetic engineering] Inserting new genes into plant cells - new gene transfer methods
* [http://www.wikiposon.org A wiki specially dedicated to transposable elements and their classification]
* [http://www.girinst.org/ Repbase] - A database of transposable element sequences
* [http://www.dnai.org/c/index.html DNA Interactive]
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