Transposable elements (TEs) or "jumping genes" historically have been disparaged as a class of "junk DNA" in mammalian genomes (1,2). The advent of whole genome DNA sequencing, in conjunction with molecular genetic, biochemical, and modern genomic and functional studies, is revealing that TEs are biologically important components of mammalian genomes. TEs are classified by whether they mobilize via a DNA or an RNA intermediate (detailed in (3)). Classical DNA transposons, such as the maize Activator/ Dissociation (Ac/Ds) elements originally discovered by Barbara McClintock, move via a DNA intermediate (4,5). Their mobility (i.e., transposition) can impact organismal phenotypes such as corn kernel variegation. Retrotransposons, the predominant class of TEs in most mammalian genomes, mobilize via an RNA intermediate by a process termed retrotransposition (6).The completion of the human genome reference sequence (HGR) (7, 8) confirmed the results of DNA hybridization-based re-annealing studies (9, 10) and revealed that retrotransposons have been a major force in shaping the structure and function of mammalian genomes. The mobility of non-long terminal repeat (non-LTR) retrotransposons, namely autonomously active Long INterspersed Element-1 sequences (LINE-1s, also known proteins can work efficiently in trans, it is formally possible that trans-complementation might allow the assembly of functional virus-like particles from partially defective HERVs, allowing the generation of new retrotransposition events. Advances in DNA sequencing technologies may reveal rare, active HERV-K elements or de novo germline or somatic HERV-K retrotransposition events in individual human genomes.LTR-retrotransposons are present at greater than 600,000 copies in mouse DNA and comprise approximately 10% of the genome (21). In contrast to the human genome, the mouse genome contains multiple, active ERV subfamilies (reviewed in (50, 51)). These include autonomously active Mus D and intracisternal A particle (IAP) elements, as well as non-autonomous early transposons (ETns) and mammalian apparent LTR retrotransposons (MALRs). It is estimated that ERV insertions are responsible for approximately ten percent of spontaneously arising mouse mutations (reviewed in (51)) (discussed in greater detail in other Chapters of Mobile DNA III).
LINE-1 Retrotransposons: abundance and structureA brief overview of human LINE-1 evolution and nomenclature-LINE-1 retrotransposons have been amplifying in mammalian genomes for greater than 160 million years (52-54). In humans, the vast majority of LINE-1 sequences have amplified since the divergence of the ancestral mouse and human lineages approximately 65-75 million years ago (7). As a consequence, LINE-1-derived sequences now account for approximately 17% of human genomic DNA (7) (Figure 1).Sequence comparisons between individual genomic LINE-1 sequences and a consensus sequence derived from modern, active LINE-1s can be used to estimate the age of genomic LINE-1s. These analyses uncovered sixteen LINE-1 pri...