Aside from homologous recombination, the overall stability of the genome is interrupted by mobile sequences called transposable elements or transposons. There are different classes of distinct DNA sequences that are able to transport themselves to other locations within the genome. This process utilizes recombination but does not result in an exchange. Rather, 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. Transposons may be a major source of evolutionary changes in the genome. In some cases they cause disease when inserted into a functioning gene. Three examples are presented below: insertion sequences (IS), transposons (Tn), and retroelements transposing via an RNA intermediate.
A. Insertion sequences (IS) and transposons (Tn)
A characteristic feature of IS transposition is the presence of a pair of short direct repeats of target DNA at either end. The IS itself carries inverted repeats of about 9–13 bp at both ends and depending on the particular class consists of about 750–1500 bp, which contain a single long coding region for transposase (the enzyme responsible for transposition of mobile sequences). Target selection is either random or at particular sites. The presence of inverted terminal repeats and the short direct repeats of host DNA result in a characteristic structure (1). Transposons carry in addition a central region with genetic markers unrelated to transposition, e.g., antibiotic resistance (2). They are flanked either by direct repeats (same direction) or by inverted repeats (opposite direction, 3).
B. Replicative and nonreplicative transposition
With replicative transposition, the original transposon remains in place and creates a new copy of itself, which inserts into a recipient site elsewhere. Thus, this mechanism leads to an increase in the number of copies of the transposon in the genome. This type 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.
C. 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 shown. Endogenous retroviruses , are sequences that resemble retroviruses but cannot infect new cells and are restricted to one genome. Non viral 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.