哺乳动物中的 L1 镶嵌现象：程度、影响和演化。

L1 Mosaicism in Mammals: Extent, Effects, and Evolution.

机构信息

Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia; Mater Research Institute - University of Queensland, Translational Research Institute (TRI) Building, Woolloongabba, QLD 4102, Australia.

Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK; Department of Genomic Medicine, Centre for Genomics and Oncology (Pfizer-University of Granada and Andalusian Regional Government), Health Technology Park (PTS) Granada, 18016 Granada, Spain.

出版信息

Trends Genet. 2017 Nov;33(11):802-816. doi: 10.1016/j.tig.2017.07.004. Epub 2017 Aug 7.

DOI:10.1016/j.tig.2017.07.004

PMID:28797643

Abstract

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.

摘要

长散布元件 1（LINE-1，long interspersed element 1）是一种转座元件，已广泛定植于哺乳动物的种系中。L1 反转录转座也会发生在体细胞中，导致基因组镶嵌性，以及癌症。然而，在个体发生过程中由 L1 驱动的镶嵌性的程度尚不清楚。我们在这里讨论了最近的实验数据，这些数据至少充分证实了早期胚胎发育和神经细胞中存在 L1 镶嵌性，包括有丝分裂后神经元。我们还考虑了体细胞 L1 插入神经元的可能生物学影响、在特定时空龛中高度活跃（“热点”）的供体 L1 的存在，以及驱动神经元镶嵌性的供体 L1 的进化选择。