The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Molecular archeology of L1 insertions in the human genome
Open accessAbstract
BACKGROUND: As the rough draft of the human genome sequence nears a finished product and other genome-sequencing projects accumulate sequence data exponentially, bioinformatics is emerging as an important tool for studies of transposon biology. In particular, L1 elements exhibit a variety of sequence structures after insertion into the human genome that are amenable to computational analysis. We carried out a detailed analysis of the anatomy and distribution of L1 elements in the human genome using a new computer program, TSDfinder, designed to identify transposon boundaries precisely. RESULTS: Structural variants of L1 elements shared similar trends in the length and quality of their target site duplications (TSDs) and poly(A) tails. Furthermore, we found no correlation between the composition and genomic location of the pre-insertion locus and the resulting anatomy of the L1 insertion. We verified that L1 insertions with TSDs have the 5'-TTAAAA-3' cleavage site associated with L1 endonuclease activity. In addition, the second target DNA cut required for L1 insertion weakly matches the consensus pattern TTAAAA. On the other hand, the L1-internal breakpoints of deleted and inverted L1 elements do not resemble L1 endonuclease cleavage sites. Finally, the genome sequence data indicate that whereas singly inverted elements are common, doubly inverted elements are almost never found. CONCLUSIONS: The sequence data give no indication that the creation of L1 structural variants depends on characteristics of the insertion locus. In addition, the formation of 5' truncated and 5' inverted L1s are probably not due to the action of the L1 endonuclease.
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“As the vast majority of L1s in the human genome are 5′ truncated (average L1 length is approximately 900bp, 90-95% of all L1s are 5′trunctated), this analysis was unsurprisingly skewed towards the 3′ end of L1s.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [53]
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Cites
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MethodBLAST 2 Sequences, a new tool for comparing protein and nucleotide sequences
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“L1 poly(A) tails During the process of TPRT, whereby a copy of an L1 is inserted into the genome, reverse transcription is believed to be primed on the poly(A) tail of the L1 transcript [12,14,17,27].”
BackgroundHuman L1 retrotransposon encodes a conserved endonuclease required for retrotransposition
Feng, Q., Moran, J. V., Kazazian, H. H., & Boeke, J. D. (1996) · Cell · doi:10.1016/s0092-8674(00)81997-2 · Cited by 1,139 · cited 7×
“The functional significance of ORF1 is not clear, whereas ORF2 contains three domains critical for L1 propagation: endonuclease [12], reverse transcriptase [7,13], and a 3 ́-terminal Zn finger-like domain [14].”
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Lahn, B. T., & Page, D. C. (1999) · Science · doi:10.1126/science.286.5441.964 · Cited by 1,010 · cited 1×
“Furthermore, the concentration of L1s with TSDs on the p arm of the X chromosome is lower than that on the q arm (Figure 8). Lahn and Page [ 52 ] have hypothesized that the distal p arm is the site of the youngest evolutionary strata on the X chromosome, indicating that the X and Y chromosomes actively recombined at t…”
Background
Research works printed but not linked: 4
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Items 201–238 of 238
Alu elements and primate genomics
McLain, A. T. (2013) · doi:10.31390/gradschool_dissertations.3287
A comprehensive analysis of human Pre-Ta LINE-1 and Ya-lineage Alu mobile elements
Otieno, A. C. (2005) · doi:10.31390/gradschool_dissertations.2171
“A similar insertion site preference was observed for 2 kb sequence blocks as well as for the previously reported L1 Ta subfamily (Myers et. al 2002) and other L1 subfamilies (Szak et al. 2002).”
MethodNon-canonical retrotransposon insertions: alternative pathways to integration
Srikanta, D. (2009) · Louisiana State University · doi:10.31390/gradschool_dissertations.3823
“This 6kb element is made up of a 5‟ UTR, ORF1 (open reading frame), ORF2, and a 3‟ UTR followed by a variable length poly (A) tail and flanked by target site duplications (TSDs) (Kazazian and Moran 1998; Szak et al. 2002).”
BackgroundRetrotransposon mediated genomic fluidity in the human and chimpanzee lineages
Han, K. (2006) · Louisiana State University · doi:10.31390/gradschool_dissertations.807
“Two chimpanzee loci (LC26 and LC27) also presumably resulted from 5’ truncation/inversion events, with overlapping junctions between the inverted segments (Szak et al. 2002).”
BackgroundMethodResultInfluentialA comprehensive analysis of recently integrated human LINE-1 mobile elements
Myers, J. S. (2003) · doi:10.31390/gradschool_dissertations.266
“A similar insertion site preference was observed for 2 kb sequence blocks as well as for the previously reported L1 Ta subfamily (Myers et al. 2002) and other L1 subfamilies (Szak et al. 2002).”
BackgroundConsequences of Alu-mediated recombination events
da Silva, A. C. C. T. (2012) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/15md-sp14
Retrotransposon-mediated genomic dynamism
Meyer, T. J. (2010) · doi:10.31390/gradschool_dissertations.2448
Retrotransposon-mediated instability in the human genome
Sen, S. K. (2008) · Louisiana State University · doi:10.31390/gradschool_dissertations.1306
“Singlestranded regions remaining in the target DNA at either end are filled in to create target site duplications (TSDs), structural hallmarks of the TPRT process which have been used in the computational location of L1 insertions (Szak et al. 2002).”
BackgroundMethodResultInfluentialThe Contribution of Retrotransposons to the Transcriptomes of Murine Somatic Cells
Gardner, J. (2017) · Apollo (University of Cambridge) · doi:10.17863/cam.41133
“In practice, this process is often imperfect, causing truncations and other mutations in the new retrotransposon copy [32,33].”
BackgroundL1 is dynamic during neurogenesis
Salvador‐Palomeque, C. (2019) · The University of Queensland · doi:10.14264/uql.2020.75
Stribinskis, V., & Ramos, K. S. (2010) · Elsevier eBooks · doi:10.1016/b978-0-08-046884-6.00222-0
The role of Transposable Elements in the Human Genome and their contribution to Evolution
van Ravesteyn, T. W. (2013) · Utrecht University Repository (Utrecht University)
Miller, T. L. A. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.46.2022.tde-26082022-132302
Ketola, K., Kaljunen, H., Taavitsainen, S., Kaarijärvi, R., Järvelä, E., Rodríguez–Martín, B., Haase, K., Woodcock, D. J., Tubío, J. M. C., Wedge, D. C., et al. (2023) · doi:10.1158/0008-5472.22362521
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Exploring Alu -Driven DNA Transductions in the Primate GenomesPreprint
Halabian, R., Storer, J. M., Hoyt, S. J., Hartley, G. A., Brosius, J., O'Neill, R. J. W., & Makałowski, W. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.29.591526
Exploring Alu-Driven DNA Transductions in the Primate GenomesPreprint
Halabian, R., Storer, J. M., Hoyt, S. J., Hartley, G. A., Brosius, J., O'Neill, R. J. W., & Makałowski, W. (2024) · Research Square · doi:10.21203/rs.3.rs-4595082/v1
Progress of research on the structure and function of RNA in R2 retrotransposon
Shun-Qing, T. A. N., Yun, Y. A. N. G., Yang, Q., & Liu, J. (2025) · Scientia Sinica Vitae · doi:10.1360/ssv-2025-0147
Image-based DNA sequencing encoding for detecting low-mosaicism somatic mobile element insertions
Tan, M., Lin, Z., Chen, Z., Zhou, H., Park, J., He, Z., Lee, E. A., Gao, Z., & Zhu, X. (2025) · Nature Communications · doi:10.1038/s41467-025-64237-w
“We fi rstinvestigatedthesupportingreadpositionsintheL1 consensus sequence because frequent 5 ’ truncations and intact 3 ’ -end are both hallmarks of true L1 retrotranspositions 57 .”
Li, S., Gozashti, L., Connelly, C., Goubert, C., Aston, K., Gleeson, J. G., Quinlan, A. R., Yang, X., & Sudmant, P. H. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.10.25.684559 · Cited by 1
“ORF2p-mediated TPRT yields TSDs between 6 and 22 nt that are enriched in adenosine content at the proximal positions of the insertion motif region (Szak et al. 2002; Konkel et al. 2015; Ewing et al. 2020).”
Additional file 2 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.24709114
Additional file 5 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26647566
Additional file 4 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26647563
Additional file 7 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26647572
Additional file 9 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26647578
Additional file 8 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26647575
Additional file 2 of Unbiased proteomic mapping of the LINE-1 promoter using CRISPR Cas9
Briggs, E. M., Mita, P., Sun, X., Ha, S., Vasilyev, N., Leopold, Z. R., Nudler, E., Boeke, J. D., & Logan, S. K. (2021) · Figshare · doi:10.6084/m9.figshare.16417412
Self-citationAdditional file 6 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26647569
Additional file 1 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2023) · Figshare · doi:10.6084/m9.figshare.24709060
Additional file 3 of An intronic LINE-1 regulates IFNAR1 expression in human immune cells
Buttler, C. A., Ramirez, D., Dowell, R. D., & Chuong, E. B. (2024) · Figshare · doi:10.6084/m9.figshare.26647560
Additional file 1 of Unbiased proteomic mapping of the LINE-1 promoter using CRISPR Cas9
Briggs, E. M., Mita, P., Sun, X., Ha, S., Vasilyev, N., Leopold, Z. R., Nudler, E., Boeke, J. D., & Logan, S. K. (2021) · Figshare · doi:10.6084/m9.figshare.16417409
Self-citationMosaicLev: modified Levenshtein distance for mobile element-aware genome comparison
Stoltz, H., & Kuhlman, T. E. (2026) · Bioinformatics Advances · doi:10.1093/bioadv/vbag261
“Some L1 insertions lack part of their 5’ end because the reverse transcription process can terminate prematurely (Szak et al. 2002, Wicker et al. 2007).”
Transposon regulation upon dynamic loss of DNA methylation
Walter, M. (2015) · theses.fr (ABES) · doi:10.70675/275812b8z11e8z4408zbf26zafee926bbb1a
Etude de transferts horizontaux de matériel génétique entre virus et animaux
Loiseau, V. (2020) · theses.fr (ABES) · doi:10.70675/a5247aaazc9b6z4f6fza3e2z0c21dc846ed9
Yang, L., Nematbakhsh, S., Norseen, A., & McLaughlin, R. N. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.14.725010
“…singleton LINE-1s increase in frequency, while many accumulate internal mutations, including SNPs, indels, and rearrangements that convert them into present-but-interrupted alleles, a pattern consistent with prior analyses of LINE-1 insertion structure and retrotransposition intermediates [38,39].”
NAKATSUKA, Y., & Ohshima, K. (2026) · Biology · doi:10.3390/biology15120927
“As commonly observed in other LINEs [27], we observed numerous truncated copies of the Bov-B LINE, which is approximately 3.5 kb in full length.”
InfluentialCo-option of retrotransposons promotes antibody diversification
Lauring, M. C., Yang, M., Sarode, A. Y., Wang, J., Ni, Z., Froehlich, K. A., Zhang, W., Wahed, S., Zheng, S., Goff, S. P., et al. (2026) · Cell · doi:10.1016/j.cell.2026.07.021
Metadata
- Authors
- Szak, S. T., Pickeral, O. K., Makalowski, W., Boguski, M. S., Landsman, D., & Boeke, J. D.
- Affiliations
- National Institutes of Health (US)
- Human Genome Sciences (United States) (US)
- Johns Hopkins University (US)
- Corresponding author
- Boeke, Jef D
- Venue
- Genome Biology
- Published
- 2002-09-19
- Volume
- 3
- Issue
- 10
- Pages
- research0052-research0052
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC134481
- OpenAlex
- W2139253234
- Cited by
- 230
- References
- 55
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 6 · 2023: 10 · 2022: 9 · 2021: 9 · 2020: 2 · 2019: 4 · 2018: 7 · 2017: 10 · 2016: 10 · 2015: 12 · 2014: 17 · 2013: 9 · 2012: 6
- FWCI
- 12.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genome biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA-16519, P01CA016519)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
- Keywords
- LINE-1 retrotransposons, human genome, transposon insertion, target site duplication, poly(A) tail, structural variants
- MeSH terms
- Algorithms, Base Sequence, Binding Sites, Humans, Poly A, Recombination, Genetic, Genome, Human, Mutagenesis, Insertional, Retroelements, Computational Biology
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