TY - JOUR
T1 - Circular DNA elements of chromosomal origin are common in healthy human somatic tissue
AU - Møller, Henrik Devitt
AU - Mohiyuddin, Marghoob
AU - Prada-Luengo, Iñigo
AU - Sailani, M. Reza
AU - Halling, Jens Frey
AU - Plomgaard, Peter
AU - Maretty, Lasse
AU - Hansen, Anders Johannes
AU - Snyder, Michael P.
AU - Pilegaard, Henriette
AU - Lam, Hugo Y.K.
AU - Regenberg, Birgitte
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The human genome is generally organized into stable chromosomes, and only tumor cells are known to accumulate kilobase (kb)-sized extrachromosomal circular DNA elements (eccDNAs). 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. Transcription from eccDNAs suggests that eccDNAs reside in nuclei and recurrence of certain eccDNAs in several individuals implies DNA circularization hotspots. Gene-rich chromosomes 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.
AB - The human genome is generally organized into stable chromosomes, and only tumor cells are known to accumulate kilobase (kb)-sized extrachromosomal circular DNA elements (eccDNAs). 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. Transcription from eccDNAs suggests that eccDNAs reside in nuclei and recurrence of certain eccDNAs in several individuals implies DNA circularization hotspots. Gene-rich chromosomes 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.
UR - http://www.scopus.com/inward/record.url?scp=85044198490&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-03369-8
DO - 10.1038/s41467-018-03369-8
M3 - Journal article
C2 - 29540679
AN - SCOPUS:85044198490
VL - 9
SP - 1069
JO - Nature Communications
JF - Nature Communications
SN - 2041-1722
IS - 1
ER -