Transposition

Transposition
Transposition is a widespread spontaneous process in living organisms by which a DNA sequence inserts itself at a new location in the genome. This type of DNA sequence is called a transposon or transposable element. Barbara McClintock first discovered transposable elements in corn in the 1940s It does not have any sequence relationship with the target site. Transposons are a major source of genetic variation. They play an important role in the evolution of genomes.

 Tranposition utilizes recombination, but does not result in an exchange. Instead, a transposon moves directly from one site of the genome to another without an intermediary such as plasmid or phage DNA This results in rearrangements that create new sequences and change the functions of target sequences. In some cases, they cause disease, when inserted into a functioning gene.

 In some cases, transposition is conservative: the transposons move without copying themselves. They are liberated from the donor site by double strand breaks in the DNA. In other cases, transposition is replicative: a copy of the transposon is inserted while the original stays in place. This mechanism involves only single strand breaks of the DNA at the donor site.

Examples - different classes of transposons

Three are presented below: Insertion sequences (IS), Replicative and nonreplicative transposons (Tn), and transpositions of retroelements via RNA intermediates.

 The first transposable elements discovered in bacteria were called insertion sequences or IS elements. These are the simplest transposons. The host DNA contains a target site of about 410 base pairs. The selection of the target site of the host DNA is either random or selective for particular sites. The insertion sequence (IS) consists of about 7001500 bp, depending on the particular class. It contains a transposase gene encoding the enzyme responsible for transposition of mobile sequences. The inverted repeats signal the transposing enzyme that it is at the ends of the IS element. The central region of the IS element contains a gene or genes for the transposing event

Insertion sequences (IS)

 It is flanked by inverted repeats of about 9 bp at both ends. This is a characteristic feature of IS transposition. The IS inserts itself at the target site by means of the transposase activity. Transposons (Tn) may contain other genes, such as for antibiotic resistance, and have direct or inverted repeats at either end. Direct repeats are identical or closely related sequences oriented in the same direction. Inverted repeats are oriented in opposite directions.

 The target site that the transposable element moves to is not a specific sequence. It becomes a direct repeat flanking the IS element only after insertion, giving rise to a model of insertion. The target site is cut in a staggered fashion, leaving single stranded ends. The IS element is then inserted between the single-stranded ends. Repair processes convert the two single-stranded tails to double-stranded segments and, hence, to direct flanking repeats.

Replicative and nonreplicative transposition

In replicative transposition, the donor transposon remains in place and creates a new copy of itself, which inserts into a recipient site elsewhere. This mechanism leads to an increase in the number of copies of the transposon in the genome. It involves two enzymatic activities: a transposase, acting on the ends of the original transposon, and resolvase, acting on the duplicated copies.

 In nonreplicative transposition, the transposing element itself moves as a physical entity directly to another site. The donor site is either repaired (in eukaryotes) or may be destroyed (in bacteria) if more than one copy of the chromosome is present.

Transposition of retroelements
Retrotransposition requires synthesis of an RNA copy of the inserted retroelement. Retroviruses, including the human immunodeficiency virus and RNA tumor viruses, are important retroelements. The first step in retrotransposition is the synthesis of an RNA copy of the inserted retroelement, followed by reverse transcription up to the polyadenylation sequence in the 3 long terminal repeat (3 LTR).

 Three important classes of mammalian transposons that undergo or have undergone retrotransposition through an RNA intermediary are Endogenous retroviruses are sequences that resemble retroviruses but cannot infect new cells and are restricted to one genome. Nonviral retrotransposons lack LTRs and usually other parts of retroviruses. Both types contain reverse transcriptase and are therefore capable of independent transposition.

 Processed pseudogenes or retropseudogenes lack reverse transcriptase and cannot transpose independently. They contain two groups: low copy number of processed pseudogenes transcribed by RNA polymerase II and high copy number of mammalian SINE sequences, such as human Alu and the mouse B1 repeat families. One in 600 mutations are estimated to arise from retrotransposon-mediated insertion

Composite Transposons
A composite transposon consists of a central region surrounded by two IS elements. The central region usually contains bacterial genes, frequently antibiotic resistance loci. For example the composite transposon Tn10 contains the genes for transposase and resolvase, as well as the bacterial gene for -lactamase, which confers resistance to ampicillin.

 The IS elements at the two ends can be identical or different; they can be in the same or different orientations; They can be similar to known IS elements or different from any freely existing IS elements. In the latter case, they are called Is like elements. Two IS elements can transpose virtually any region between them. In fact, composite transposons most likely came into being when two IS elements became located near each other.

 Two IS elements in a plasmid can transpose either of the two regions between them. In this case shown, either the Tn10 transposon or the reverse transposon (other genes) is transposed.

res sites: Sites on the two copies of a transposon in a cointegrate, between which crossing over occurs to accomplish resolution.