Journal article
Quantitative assessment reveals the dominance of duplicated sequences in germline-derived extrachromosomal circular DNA
Proceedings of the National Academy of Sciences - PNAS, Vol.118(47), p.1
11/23/2021
DOI: 10.1073/pnas.2102842118
PMCID: PMC8617514
PMID: 34789574
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.
Details
- Title: Subtitle
- Quantitative assessment reveals the dominance of duplicated sequences in germline-derived extrachromosomal circular DNA
- Creators
- Lila Mouakkad-Montoya - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048Michael M Murata - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048Arvis Sulovari - HHMI, University of Washington School of Medicine, Seattle, WA 98195Ryusuke Suzuki - Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048Beth Osia - Department of Biology, University of Iowa, Iowa City, IA 52242Anna Malkova - Department of Biology, University of Iowa, Iowa City, IA 52242Makoto Katsumata - Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA 90048Armando E Giuliano - Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048Evan E Eichler - HHMI, University of Washington School of Medicine, Seattle, WA 98195Hisashi Tanaka - Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.118(47), p.1
- DOI
- 10.1073/pnas.2102842118
- PMID
- 34789574
- PMCID
- PMC8617514
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Grant note
- R01 CA149385 / NCI NIH HHS R03 CA188111 / NCI NIH HHS
- Language
- English
- Date published
- 11/23/2021
- Academic Unit
- Biology
- Record Identifier
- 9984217529502771
Metrics
7 Record Views