ArticleProceedings of the National Academy of Sciences of the United States of America2021
Quantitative assessment reveals the dominance of duplicated sequences in germline-derived extrachromosomal circular DNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- The potential clinical implications of extrachromosomal circular DNA as a biomarker.Genes & diseases · 2026Review
- Highly mutagenic copying of telomeric circles promotes ALT establishment.Nature communications · 2026Article
- Unveiling the mysteries of extrachromosomal circular DNA: from generation to clinical relevance in human cancers and health.Molecular cancer · 2024Review
- Long extrachromosomal circular DNA identification by fusing sequence-derived features of physicochemical properties and nucleotide distribution patterns.Scientific reports · 2024Article
- Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction.Protein & cell · 2024Review
- Microhomology-mediated circular DNA formation from oligonucleosomal fragments during spermatogenesis.eLife · 2023Article
- Evolutionary honing in and mutational replacement: how long-term directed mutational responses to specific environmental pressures are possible.Theory in biosciences = Theorie in den Biowissenschaften · 2023Review
- A Quick Method to Synthesize Extrachromosomal Circular DNA In Vitro.Molecules (Basel, Switzerland) · 2023Article
- AlcoR: alignment-free simulation, mapping, and visualization of low-complexity regions in biological data.GigaScience · 2022Article
- CReSIL: accurate identification of extrachromosomal circular DNA from long-read sequences.Briefings in bioinformatics · 2022Article
- SVA Retrotransposons and a Low Copy Repeat in Humans and Great Apes: A Mobile Connection.Molecular biology and evolution · 2022Article
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Authors and funding
10 authors.
Funding
Abstract
Extrachromosomal circular DNA (eccDNA) originates from linear chromosomal DNA in various human tissues under physiological and disease conditions. The genomic origins of eccDNA have largely been investigated using in vitro-amplified DNA. However, in vitro amplification obscures quantitative information by skewing the total population stoichiometry. In addition, the analyses have focused on eccDNA stemming from single-copy genomic regions, leaving eccDNA from multicopy regions unexamined. To address these issues, we isolated eccDNA without in vitro amplification (naïve small circular DNA, nscDNA) and assessed the populations quantitatively by integrated genomic, molecular, and cytogenetic approaches. nscDNA of up to tens of kilobases were successfully enriched by our approach and were predominantly derived from multicopy genomic regions including segmental duplications (SDs). SDs, which account for 5% of the human genome and are hotspots for copy number variations, were significantly overrepresented in sperm nscDNA, with three times more sequencing reads derived from SDs than from the entire single-copy regions. SDs were also overrepresented in mouse sperm nscDNA, which we estimated to comprise 0.2% of nuclear DNA. Considering that eccDNA can be integrated into chromosomes, germline-derived nscDNA may be a mediator of genome diversity.
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