L1 Mosaicism in Mammals: Extent, Effects, and Evolution

• Published in: Trends in genetics 2017-11, Vol.33 (11), p.802-816
• Main Authors: Faulkner, Geoffrey J., Garcia-Perez, Jose L.
• Format: Article
• Language: English
• Subjects: Animals; embryogenesis; Embryonic Development - genetics; Humans; LINE-1; Long Interspersed Nucleotide Elements; Mammals - genetics; Mosaicism; neurogenesis; Neurons - metabolism; Retroelements; retrotransposon
• ISSN: 0168-9525
• DOI: 10.1016/j.tig.2017.07.004

The retrotransposon LINE-1 (long interspersed element 1, L1) is a transposable element that has extensively colonized the mammalian germline. L1 retrotransposition can also occur in somatic cells, causing genomic mosaicism, as well as in cancer. However, the extent of L1-driven mosaicism arising during ontogenesis is unclear. We discuss here recent experimental data which, at a minimum, fully substantiate L1 mosaicism in early embryonic development and neural cells, including post-mitotic neurons. We also consider the possible biological impact of somatic L1 insertions in neurons, the existence of donor L1s that are highly active (‘hot’) in specific spatiotemporal niches, and the evolutionary selection of donor L1s driving neuronal mosaicism. L1 retrotransposons can mobilize during embryogenesis, and in the neuronal lineage, causing somatic genome mosaicism. Genomic analysis of endogenous L1 mobilization in mouse pedigrees, and L1 transgenic rodents, has revealed that the early embryo, before germ cell specification, is the primary niche for the accumulation of new, heritable L1 insertions. Neuronal progenitor cells and post-mitotic neurons accommodate engineered L1 retrotransposition, but other cell lineages support limited or no L1 activity in the physiological conditions tested to date. L1 retrotransposition clearly occurs in the brain, based on data obtained from engineered L1 reporter systems and single-cell genomic analysis, but the relevant techniques and estimated L1 mobilization rates vary considerably. Donor L1s can be differentially active in germline and somatic cells, potentially influencing the evolutionary selection of donor L1s that are highly active in the brain.