Genomes are surprisingly plastic, containing a variety of different kinds of DNA that can move from place to place. These mobile elements generally move by site-specific recombination—that is, by the action of a specialized recombinase, usually encoded by the mobile element, on special DNA sites at the ends of the element where recombination occurs; these recombination reactions can occur by a variety of mechanisms. One type of mobile DNA present in virtually all organisms examined are transposable elements. A major pathway for transposition is a DNA-based mechanism in which the transposon is excised from flanking donor site DNA by a double-strand break; alternatively, a DNA copy of the element is made by reverse transcription of an RNA transcribed from a chromosomal copy of the element. Both these processes result in the production of exposed 3′OHs at the ends of the mobile DNA segment. These exposed 3′OH ends are then joined to the target DNA, covalently linking the mobile element to its new site of insertion. Transposition is used by viruses to join the element to the genome of a newly infected cell. Other transposable elements move within a cell and often encode determinants, such as antibiotic-resistance genes that affect the cell. Nonviral transposable elements can also be dispersed between cells by translocating onto plasmids or viruses that move from cell to cell.
Mobile elements include, but are not limited to, transposable elements—that is, those elements that move between nonhomologous sites via the recombination reaction called transposition, and transposable elements may be called mobile elements. There are a number of mobile DNA segments that are not transposable elements and that translocate by mechanisms other than transposition.
Another reaction in which DNA segments can rearrange to make new genes occurs by a pathway distinct from transposition, but involves a recombinase that can carry out transposition-type reactions (1, 2). VDJ recombination is an ordered set of deletion reactions that assembles immunoglobulin genes from multiple gene segments, providing incredible diversity in the immune system (3) (see Gene Rearrangement). As in transposition, the breakage and joining steps also involve DNA breakage reactions to expose 3′OH ends, followed by the joining of these 3′OH ends to intramolecular targets.
Another distinct kind of element translocation that occurs between nonhomologous sites is the movement of polyA+ elements such as the LINES and SINES of mammalian genomes that lack all inverted terminal repeats (4). Translocation involves an element-generated nick in the target DNA that serves as a primer for the in situ reverse transcription of an element RNA, resulting in a new DNA copy of the element at a new chromosomal location.
Another nontransposable element mobile DNA is exemplified by the lambda phage that integrates into the bacterial chromosome to become part of the chromosome during lysogeny and then excises from the chromosome to enter the lytic phase. These recombination reactions occur at specialized sites on both the viral and chromosomal genomes; these sites are related to each other by protein binding sites and a short region of homology. Recombination occurs by simple breakage and joining reactions at each site (5, 6), in a reaction called conservative site-specific recombination (CSSR). This is a very distinct reaction from transposition, where the two transposon ends interact with a nonhomologous target site. Other CSSR-mediated reactions include the inversion of bacterial chromosomal segments to alternate between two configurations for differential gene expression and the monomerization of various dimeric DNA molecules, from plasmids to chromosomes. Yet another kind of reaction that can move different DNA sequences from place to place involves the introduction of gap at a particular site by a double-strand break that undergoes exonucleolytic trimming, followed by the filling of this gap via pairing and DNA replication, with information from a related site containing similar but distinct sequences (7).
