Circular DNA in the human germline and its association with recombination

Research output: Contribution to journalJournal articleResearchpeer-review

Extrachromosomal circular DNA (eccDNA) is common in somatic tissue, but its existence and effects in the human germline are unexplored. We used microscopy, long-read DNA sequencing, and new analytic methods to document thousands of eccDNAs from human sperm. EccDNAs derived from all genomic regions and mostly contained a single DNA fragment, although some consisted of multiple fragments. The generation of eccDNA inversely correlates with the meiotic recombination rate, and chromosomes with high coding-gene density and Alu element abundance form the least eccDNA. Analysis of insertions in human genomes further indicates that eccDNA can persist in the human germline when the circular molecules reinsert themselves into the chromosomes. Our results suggest that eccDNA has transient and permanent effects on the germline. They explain how differences in the physical and genetic map might arise and offer an explanation of how Alu elements coevolved with genes to protect genome integrity against deleterious mutations producing eccDNA.

Original languageEnglish
JournalMolecular Cell
Issue number1
Pages (from-to)209-217.e7
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

    Research areas

  • amplification, complex rearrangements, DM, double minutes, eccDNA, evolution, long-read sequencing, structural variation, translocation

ID: 290116671