Widespread somatic L1 retrotransposition in normal colorectal epithelium

Chang Hyun Nam, Jeonghwan Youk, Jeong Yeon Kim, Joonoh Lim, Jung Woo Park, Soo A. Oh, Hyun Jung Lee, Ji Won Park, Hyein Won, Yunah Lee, Seung Yong Jeong, Dong Sung Lee, Ji Won Oh, Jinju Han, Junehawk Lee, Hyun Woo Kwon, Min Jung Kim, Young Seok Ju

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Throughout an individual’s lifetime, genomic alterations accumulate in somatic cells 1–11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome 12–14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.

Original languageEnglish
Pages (from-to)540-547
Number of pages8
Issue number7961
StatePublished - 18 May 2023


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