Circular DNA Elements of Chromosomal Origin Are Common in Healthy Human Somatic Tissue

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Mar 16

PMID 29540679

Citations 170

Authors

Henrik Devitt Moller

Marghoob Mohiyuddin

Inigo Prada-Luengo

M Reza Sailani

Jens Frey Halling

Peter Plomgaard

Lasse Maretty

Anders Johannes Hansen

Michael P Snyder

Henriette Pilegaard

Hugo Y K Lam

Birgitte Regenberg

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Molecular mechanisms of extrachromosomal circular DNA formation.

Eugen-Olsen R, Hariprakash J, Oestergaard V, Regenberg B Nucleic Acids Res. 2025; 53(5).

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