Circular DNA in the human germline and its association with recombination
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Molecular Cell |
| Vol/bind | 82 |
| Udgave nummer | 1 |
| Sider (fra-til) | 209-217.e7 |
| ISSN | 1097-2765 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
We thank Jacobus Jan “Koos” Boomsma and Guojie Zhang, Department of Biology, Section for Ecology and Evolution at the University of Copenhagen for critical reading of the manuscript. For technical assistance, we thank Sefa Alizadeh for purifying eccDNA and Pablo Hernandez-Varas for assisting with microscopy. This work is supported by Independent Research Fund Denmark ( FNU 6108-00171B to the project, I.P.-L. and B.R.), the VILLUM Foundation ( 00023247 to R.A.H. and B.R.), and the National Institute of General Medical Sciences of the National Institutes of Health ( P20GM125503 to I.N.).
Funding Information:
We thank Jacobus Jan ?Koos? Boomsma and Guojie Zhang, Department of Biology, Section for Ecology and Evolution at the University of Copenhagen for critical reading of the manuscript. For technical assistance, we thank Sefa Alizadeh for purifying eccDNA and Pablo Hernandez-Varas for assisting with microscopy. This work is supported by Independent Research Fund Denmark (FNU 6108-00171B to the project, I.P.-L. and B.R.), the VILLUM Foundation (00023247 to R.A.H. and B.R.), and the National Institute of General Medical Sciences of the National Institutes of Health (P20GM125503 to I.N.). B.R. designed the study. I.B.S. K.R.J. and T.W. performed the laboratory experiments. R.A.H. I.P.-L. and P.J. performed the computational experiments. T.W. conducted the sequencing experiments under supervision of I.N. I.N. and B.R. supervised the computational experiments. R.A.H. and B.R. analyzed the data. R.A.H. and B.R. wrote the manuscript with input from all authors. The authors declare no competing interests.
Publisher Copyright:
© 2021 Elsevier Inc.
ID: 290116671