Martin S L, Li W-L P, Furano A V, Boissinot S
Department of Cell and Developmental Biology, University of Colorado School of Medicine, Denver, CO 80045, USA.
Cytogenet Genome Res. 2005;110(1-4):223-8. doi: 10.1159/000084956.
L1 is an abundant, interspersed repeated DNA element of mammalian genomes. It has achieved its high copy number via retrotransposition. Like other non-LTR retrotransposons, L1 insertion into chromosomal DNA apparently occurs by target-site primed reverse transcription, or TPRT. L1 retrotransposition often generates elements with 5' truncations that are flanked by a duplication of the genomic target site (TSD). It is typically assumed that the 5' truncated elements are the consequence of poor processivity of the L1 reverse transcriptase. However, we find that the majority of young L1 elements from both the human and mouse genomes are truncated at sequences that can basepair with the target site. Thus, to whatever extent truncation is a consequence of poor processivity, we suggest that truncation is likely to occur when target site sequence can basepair with L1 sequence. This finding supports a model for insertion that occurs by two sequential TPRT reactions, the second of which relies upon the homology between the target site and L1. Because perfect heteroduplex formation is not required for all insertions, a dynamic relationship between the primer, template and enzyme during reverse transcription is inferred. 5' truncation may be a successful evolutionary strategy that is exploited by L1 as a means to escape host suppression of transposition.
L1是哺乳动物基因组中一种丰富的、散布的重复DNA元件。它通过逆转座作用实现了高拷贝数。与其他非LTR逆转座子一样，L1插入染色体DNA显然是通过靶位点引发的逆转录，即TPRT发生的。L1逆转座通常会产生5'端截短的元件，其两侧是基因组靶位点（TSD）的重复。通常认为5'端截短的元件是L1逆转录酶持续性差的结果。然而，我们发现来自人类和小鼠基因组的大多数年轻L1元件在能够与靶位点碱基配对的序列处被截短。因此，无论截短在何种程度上是持续性差的结果，我们认为当靶位点序列能够与L1序列碱基配对时，截短很可能会发生。这一发现支持了一种通过两个连续的TPRT反应发生插入的模型，其中第二个反应依赖于靶位点与L1之间的同源性。由于并非所有插入都需要完美的异源双链体形成，因此推断在逆转录过程中引物、模板和酶之间存在动态关系。5'端截短可能是L1利用的一种成功的进化策略，作为逃避宿主对转座抑制的一种手段。
