Fig. 3

Somatic retrotransposition can cause complex genomic mosaicism. a. Donor L1 expression and mobilization during development. A handful of L1 copies from each individual are highly active, or hot, when tested in vitro [38, 39]. Four scenarios for donor L1s mobilizing in vivo are illustrated here. Most L1s are repressed [105] during development and do not mobilize, except perhaps due to exceptional circumstances, such as the availability of an active upstream promoter (e.g. yellow donor L1) [36]. L1 promoter de-repression can however occur during development, either transiently (e.g. red and orange donor L1s) or durably (e.g. blue donor L1), leading to L1 mRNA and RNP accumulation. Retrotransposition enacted by the L1 machinery occurs as a function of donor L1 activity in a given spatiotemporal context (blue, red, orange and yellow arrowheads, matching each donor L1). b. The developmental timing of a given retrotransposition event impacts how many mature cells carry the new L1 insertion. Early embryonic L1 mobilization events (e.g. blue and red cells indicated by arrowheads and matching donor L1s by color) may be carried by numerous descendent cells, possibly in different tissues [18]. By contrast, L1 insertions arising later in development (indicated by orange, blue and yellow arrows) are more restricted in their spatiotemporal extent, and may be found in just one cell (e.g. a post-mitotic neurons). The resulting somatic genome mosaicism may disproportionately impact the brain [19–21, 23, 25, 27, 133,134,135,136,137,138], although further work is required to test whether other organs, such as the liver, also routinely carry somatic L1 insertions [72, 161]