Transposons thrive as parasites of host genomes. When mobilized, they can disrupt protein-coding genes, alter transcriptional regulatory networks, and cause chromosomal breakage and large-scale genomic rearrangement (McClintock, 1951
). Cells must therefore engage in an ongoing struggle to protect genomic integrity by guarding cellular DNA from the activity of mobile elements. Discriminating these parasites from a cell's own protein-coding genes is no small task. Individual transposons fall into many classes and bear little overall resemblance to each other. They employ myriad movement strategies, thus confounding any attempt to target a specific and distinguishable replication intermediate. Instead, our still emerging understanding points to a transposon defense that requires a working memory of each individual element. That memory appears to arise after initial colonization and a period of largely unregulated activity during which the mobility of the element, per se, is the Achilles’ heel that insures its downfall. By jumping into specific loci, transposons become trapped in a silencing program that instructs a small RNA-based immune system to selectively silence homologous elements in germ cells, thus guarding the genetic integrity of the species.
On the whole, transposon families can be categorized into a few broad classes of elements that differ in both their structure and movement strategies. The principal division separates retrotransposons (class I) from DNA transposons (class II). Retrotransposons replicate via an RNA intermediate that is reverse transcribed prior to its integration into the host genome. This class is further segregated into elements that are bounded by long terminal repeats (LTR), similar to those of retroviruses, and those that are not (non-LTR).
Non-LTR elements are subdivided into long interspersed nucleotide elements (LINEs) and short interspersed nucleotide elements (SINEs), depending upon their size and origin. Their expression is invariably driven by the combination of internal promoter and 3′ end formation signals that travel with each new full-length insertion. The autonomous members of this group, those not requiring a helper element for mobility, characteristically contain two internal open reading frames (ORFs): one directing synthesis of a DNA binding protein and the other encoding endonuclease and reverse transcriptase enzymes, which are separated posttranslationally (reviewed in Kazazian, 2004
LTR elements resemble the retroviruses from which they are apparently derived. They encode gag and pol proteins, which can mediate their replicative transfer to new sites in the genome. Consistent with their viral origins, some LTR elements can move not only within genomes but also from cell to cell. Examples are found within the gypsy
family in Drosophila
. These elements, termed infectious retroviruses or errantiviruses, possess an envelope (env) gene that enables infection of neighboring cells and even horizontal transfer among species (Kim et al., 1994
; Song et al., 1994
Unlike retrotransposons, for which each transposition event generates an additional copy of itself elsewhere in the genome, class II DNA transposons mobilize via a “cut-and-paste” mechanism. Thus, each transposition event is a zero-sum game wherein one site loses transposon information while another gains it. However, because sequences are duplicated upon element integration and because the excision site must be repaired as the element leaves, most transposition events leave scars in the form of short repeats. Autonomous DNA transposons harbor a transposase gene that recognizes the element's flanking terminal inverted repeats (TIRs) and that catalyzes both excision and reintegration. There are also nonautonomous DNA transposons that require the donation of a transposase protein from another functional element.
The diversity of transposable elements and the degree to which they burden eukaryotic genomes is remarkably variable. In mammals, transposons constitute up to 50% of the genome (reviewed in Kazazian, 2004
). In comparison, only ~5% of the Drosophila
genome is composed of mobile elements (Bergman et al., 2006
). While the Arabidopsis
genome maintains numerous members of all classes of transposable elements, the budding yeast S. cerevisiae
contains only members related to a single LTR retrotransposon family. Drosophila
harbors roughly 150 different element families. These comprise a wide variety of LTR and non-LTR retrotransposons, each of which is present in limited number within the genome. The transposon content of the mouse genome is also dominated by retroelements, but in this case by very large numbers of only a few related elements from the IAP (LTR), LINE1, and SINE B1 (non-LTR) retrotransposon families.