Circular DNA elements of chromosomal origin are
common in healthy human somatic tissue
Henrik Devitt Møller
, Marghoob Mohiyuddin
, Iñigo Prada-Luengo
, M. Reza Sailani
, Jens Frey Halling
, Lasse Maretty
, Anders Johannes Hansen
, Michael P. Snyder
, Henriette Pilegaard
Hugo Y. K. Lam
& Birgitte Regenberg
The human genome is generally organized into stable chromosomes, and only tumor cells are
known to accumulate kilobase (kb)-sized extrachromosomal circular DNA elements (eccD-
NAs). However, it must be expected that kb eccDNAs exist in normal cells as a result of
mutations. Here, we purify and sequence eccDNAs from muscle and blood samples from 16
healthy men, detecting ~100,000 unique eccDNA types from 16 million nuclei. Half of these
structures carry genes or gene fragments and the majority are smaller than 25 kb. Tran-
scription from eccDNAs suggests that eccDNAs reside in nuclei and recurrence of certain
eccDNAs in several individuals implies DNA circularization hotspots. Gene-rich chromo-
somes contribute to more eccDNAs per megabase and the most transcribed protein-coding
gene in muscle, TTN (titin), provides the most eccDNAs per gene. Thus, somatic genomes
are rich in chromosome-derived eccDNAs that may inﬂuence phenotypes through altered
gene copy numbers and transcription of full-length or truncated genes.
Department of Biology, University of Copenhagen, Copenhagen DK-2100, Denmark.
Roche Sequencing Solutions, Belmont, CA 94002, USA.
of Genetics, Center for Genomics and Personalized Medicine Stanford University, School of Medicine, Stanford, CA 94305, USA.
Department of Clinical
Biochemistry, Rigshospitalet, Copenhagen DK-2100, Denmark.
The Centre of Inﬂammation and Metabolism and the Centre for Physical Activity Research,
Rigshospitalet, University of Copenhagen, Copenhagen DK-2100, Denmark.
The Natural History Museum of Denmark, University of Copenhagen,
Copenhagen DK-1350, Denmark. Correspondence and requests for materials should be addressed to H.D.Møl. (email: firstname.lastname@example.org)
or to B.R. (email: email@example.com)