Through her pioneering work in maize, Barbara McClintock was the first to realize that eukaryotic genomes are not static entities and contain transposable elements (TEs) that have the ability to move from one chromosomal location to another1
. It now is clear that virtually all organisms harbor TEs that have amplified in copy number over evolutionary time via DNA or RNA intermediates. On occasion, TEs sporadically have been co-opted by the host to perform critical cellular functions(e.g., 2–5)
. However, most TEs likely are finely tuned genomic parasites that mobilize to ensure their own survival6–9
. The genomic revolution, coupled with new DNA sequencing technologies, now provides an unprecedented wealth of data documenting TE content and mobility in a broad array of organisms.
In multi-cellular eukaryotes, TEs must mobilize within gametes or during early development to be transmitted to future generations. In humans, there are at least 65 documented cases of diseases resulting from de novo
TE insertions; these events account for approximately 1/1000 spontaneous cases of disease in humans5, 10
. Indeed, new genomic technologies combined with cell culture based experiments have demonstrated that active TEs are more prevalent in the human population than previously appreciated11–18
. A growing body of evidence further suggests that mammalian TE integration occurs during early development19–21
. In addition, studies of neurogenesis and some forms of cancer have raised the intriguing possibility that TE activity may impact the biology of certain somatic cells12, 22–24
. It is likely that we only have observed the tip of the iceberg and still are underestimating the contribution of TE-mediated events to inter-and intra-individual structural variation in mammalian genomes.
TE mobility poses a serious challenge to host fitness. Paradoxically, TE insertions that are harmful to the host jeopardize TE survival. Thus, many TEs have evolved highly specific targeting mechanisms that direct their integration to genomic “safe havens,” thereby minimizing their damage to the host(e.g., 25–29, and references mentioned below)
. Nevertheless, host genomes have evolved potent restriction mechanisms, such as the methylation of TE DNA sequences and the expression of small RNAs or cytidine deaminases, to restrict TE activity in the germline and perhaps somatic cells(e.g., 30–33, and references mentioned below)
Interestingly, a growing number of examples suggest that TEs may become activated under certain environmental conditions, such as stress. Stress has been shown to induce TE transcription or integration, or redirect TE integration to alternative target sites34–38
. These findings are consistent with Barbara McClintock’s hypothesis that environmental challenges may induce transposition, and that transposition, in turn, may create genetic diversity to overcome threats to host survival39
We begin this review with a brief description of the types of TEs and their modes of mobility. We then describe the latest understanding of TE integration mechanisms and how the host defends against these attacks. Finally, we discuss exciting new research that suggests TE mobility may impact the biology of somatic cells. From the growing understanding of target site selection to the discovery of new active TE copies in human populations, it is clear that the field of transposon biology continues to yield new insights about genome biology.