Transposons

ODUCTION TO TRANSPOSONSover evolutionary time. These Interspersed Repeats
              (Jumping Genes)block gene conversion thereby catalyzing the
 Author: Waseem Ashfaqformation of new genes. Transposons are therefore
            Transposons are pieces of DNAan evolutionary device promoting creation of new
that can “jump” into novel positions in thegenes and protecting novel gene sequences from
genome. There are numerous different types ofbeing overwritten by similar gene sequences through
transposon which differ from each other in manygene conversion.
ways. They have been exploited very extensively inThere are three distinct types:
molecular biology research. They can insert·  Class II Transposons consisting only of DNA
themselves into DNA without requiring any similarthat moves directly from place to place.
sequence to be present in themselves and their·   Class III Transposons; also known as Miniature
“target”. This makes them powerfulInverted-repeats Transposable Elements or MITEs.
mutagens, since their insertion into a gene will·   Retrotransposons (Class I) that
generally prevent the gene from producing a           -first transcribe the DNA into RNA
functional protein. As mutagens, their effect is notand then
always completely random, as some do have          -use reverse transcriptase to make a
preferences for certain sequences or types ofDNA copy of the RNA to insert in a new location.
chromatin, and others will transpose preferentially to          Many transposons move by a "cut
adjacent regions rather than randomly throughout theand paste" process: the transposon is cut out of its
genome. Generally, a minimum of two things arelocation (like command/control-X on your computer)
required for transposition.and inserted into a new location (command
             The first is a gene whichcontrol-V). This process requires an enzyme — a
encodes transposase enzyme and which cantransposase — that is encoded within some of
recognize the ends of the transposon, excise thethese transposons. Transposase binds to:
transposon (or a copy of it) from its starting point,·  both ends of the transposon, which consist of
cut DNA randomly or semi-randomly elsewhere, andinverted repeats; that is, identical sequences reading
catalyze the movement of the transposon from itsin opposite directions.
starting point to its new target. The transposase can·   a sequence of DNA that makes up the target
be encoded either by the transposon itself (in whichsite. Some transposases require a specific sequence
case the transposon is often referred to as beingas their target site; other can insert the transposon
“autonomous”) or elsewhere – onanywhere in the genome.
another transposon, for example, or on a plasmid.     After the transposon is ligated to the host
Transposons which rely on a transposase which theyDNA, the gaps are filled in by Watson-Crick base
do not themselves carry are calledpairing. This creates identical direct repeats at each
“non-autonomous”. They occur naturally, andend of the transposon. Often transposons lose their
any autonomous transposon can be converted to agene for transposase; but as long as somewhere in
non-autonomous one by removing the transposasethe cell there is a transposon that can synthesize the
gene from it. The second requirement forenzyme, their inverted repeats are recognized and
transposition are the sequences at the ends of thethey, too, can be moved to a new location.
transposon, which are recognized by the transposase.           Retrotransposons move by a "copy
This minimal requirement for an autonomousand paste" mechanism but in contrast to the
transposon is shown below. There are many variantstransposons described above, the copy is made of
on this theme! Transposons use many differentRNA, not DNA.  The RNA copies are then
mechanisms to jump around the genome, but they alltranscribed back into DNA — using a reverse
boil down to two basic types: replicative andtranscriptase — and these are inserted into new
nonreplicative. Replicative transposons copylocations in the genome.  Many retrotransposons
themselves when they transpose, and leave onehave long terminal repeats (LTRs) at their ends that
copy at the original site while inserting the secondmay contain over 1000 base pairs in each. Like DNA
copy elsewhere. Non-replicative transposons aretransposons, retrotransposons generate direct
excised from their starting position and insertedrepeats at their new sites of insertion. In fact, it is
elsewhere in the genome.the presence of these direct repeats that often is
             In replicative transposition a), thethe clue that the intervening stretch of DNA arrived
transposon makes a copy of itself which is insertedthere by retrotransposition. 42% of the entire human
randomly in the target DNA. In non-replicativegenome consists of retrotransposons.
transposition b), the transposon excises from its            Retroviruses were first identified
original position (usually leaving a small change in the80 years ago as agents involved in the onset of 
sequence at the excision point) and reinserts atcancer. More recently the AIDS epidemic has been
random in the target DNA.shown to be due to the HIV retrovirus. In the early
They may be:1970s it was discovered that retroviruses had the
·        cause mutationsability to replicate their RNA genomes via conversion
·        Increase (or decrease) the amount ofinto DNA which became stably integrated in the DNA
DNA in the genome.of the host cell. It is only comparatively recently that
            These mobile segments of DNAretroviruses have been recognized as particularly
are sometimes called "jumping genes". They werespecialized forms of eukaryotic transposons. In
discovered by Barbara McClintock early in her career,effect they are transposons which move via RNA
for which she was awarded a Nobel prize in 1983.intermediates that usually can leave the host cells and
The chromosomal basis of heredity was already wellinfect other cells. The integrated DNA form (provirus)
established by the time McClintock began herof the retrovirus bears a marked similarity to a
graduate training in the Botany Department at Cornelltransposon.
University. Her experiments laid the groundwork for a           The transposition cycle of
serie of cytogenetic discoveries by the Cornell maizeretroviruses has other similarities to prokaryotic
genetics group between 1929 and 1935. McClintocktransposons, which suggest a distant familial
developed a method for using broken chromosomesrelationship between these two types of transposon.
to generate new mutations. Among the progeny ofCrucial intermediates in retrovirus transposition are
plants that had received a broken chromosome fromextrachromosomal DNA molecules. These are
each parent, she observed unstable mutations at angenerated by copying the RNA of the virus particle
unexpectedly high frequency, as well as a uniqueinto DNA by a retrovirus-encoded polymerase called
mutation that defined a regular site of chromosomereverse transcriptase. The extra chromosomal linear
breakage. These observations so intrigued her thatDNA is the direct precursor of the integrated element
she began an intensive investigation of theand the insertion mechanism bears a strong similarity
chromosome-breaking locus. Within several years sheto "cut and paste" transposition.
had learned enough to reach the conclusion, published            One family of transposons in the
in 1948, that the chromosome-breaking locus didfruit fly Drosophila melanogaster are called P
something unknown for any genetic locus: it movedelements. They seem to have first appeared in the
from one chromosomal location to another, aspecies only in the middle of the twentieth century.
phenomenon she called transposition.Within 50 years, they have spread through every
              Transposons are discretepopulation of the species. Transposons are also a
segments of DNA capable of moving through thewidely used tool for mutagenesis of most
genome of their host via an RNA intermediate in theexperimentally tractable organisms.
case of class I retrotransposon or via a             In bacteria, transposons can
"cut-and-paste" mechanism for class II DNAjump from chromosomal DNA to plasmid DNA and
transposons. Since transposons take advantage ofback, allowing for the transfer and permanent
their host's cellular machinery to proliferate in theaddition of genes such as those encoding antibiotic
genome and enter new hosts, transposable elementsresistance (multi-antibiotic resistant bacterial strains
can be viewed as parasitic or "selfish DNA". However,can be generated in this way). Bacterial transposons
transposons may have been beneficial for their hostsof this type belong to the Tn family. When the
as genome evolution drivers, thus providing antransposable elements lack additional genes, they are
example of molecular mutualism. Some transposableknown as insertion sequences. The most common
elements contain heat-shock like promoters and theirform of transposon in humans is the Alu sequence.
rate of transposition increases if the cell is subjectedThe Alu sequence is approximately 300 bases long
to stress, thus increasing the mutation rate underand can be found between 300,000 and a million
these conditions, which might be beneficial to the cell.times in the human genome.
           The evolution of transposons and            Mariner-like elements are another
their effect on genome evolution is currently aprominent class of transposons found in multiple
dynamic field of study. Transposons are found in allspecies including humans. The mariner transposon was
major branches of life. The study of transposablefirst discovered by Jacobson and Hartl in drosophila1.
genetic elements and transposition became theThis type-II trasposable element is known for its
central theme of her genetic experiments from theuncanny ability to be transmitted horizontally in many
mid 1940s until the end of her active research career.species. There are an estimated 14 thousand copies
This was incredulous at the time, DNA was believedof mariner in the human genome composing of 2.6
to be stable and invariable. They may or may notmillion base pairs. These characteristics of the mariner
have originated in the last universal commontransposon have inspired the science fiction novel
ancestor, or arisen independently multiple times, ortitled, "The Mariner Project."
perhaps arisen once and then spread to other References:
kingdoms by horizontal gene transfer. While 1.    McClintock, B. (June 1950). "The origin and
transposons may confer some benefits on theirbehavior of mutable loci in maize". Proc Natl Acad Sci
hosts, they are generally considered to be selfishU S A. 36 (6): 344–55.
DNA parasites that live within the genome of cellular2.    Rubin GM, Spradling AC (October 1982).
organisms. In this way, they are similar to viruses."Genetic transformation of Drosophila with
Viruses and transposons also share features in theirtransposable element vectors". Science 218 (4570):
genome structure and biochemical abilities, leading to348–53.
speculation that they share a common ancestor.3.    Wilson MH, Coates CJ, George AL (January
          Since excessive transposon activity2007). "PiggyBac transposon-mediated gene transfer
can destroy a genome, many organisms seem toin human cells". Mol. Ther. 15 (1): 139–45.
have developed mechanisms to reduce transposition4.    Mandal, P.K. & Kazazian, H.H., Jr. SnapShot:
to a manageable level. Bacteria may undergo highVertebrate transposons. Cell 135, 192-192 e1 (2008).
rates of gene deletion as part of a mechanism to5.    Kidwell, M.G. (2005). "Transposable elements.".
remove transposons and viruses from their genomesin (ed. T.R. Gregory). The Evolution of the Genome.
while eukaryotic organisms may have developed theSan Diego: Elsevier. pp. 165–221. ISBN
RNA interference (RNAi) mechanism as a way of0-12-301463-8. 
reducing transposon activity. In the nematode6.    Craig NL, Craigie R, Gellert M, and Lambowitz
Caenorhabditis elegans, some genes required forAM (ed.) (2002). Mobile DNA II. Washington, DC: ASM
RNAi also reduce transposon activity.Press. ISBN 978-1555812096. 
          Interspersed Repeats within genomes7.    Lewin B (2000). Genes VII. Oxford University
are created by transposition events accumulatingPress.. ISBN 978-0198792765.