Extrachromosomal DNA (microDNA) in Human, Mouse and Chicken

MicroDNAs are <400-base long extrachromosomal circles found in mammalian cells. Tens of thousands of microDNAs were found in all tissue types, including sperm. MicroDNAs arose preferentially from areas with high gene density, high GC content, high exon density, promoters with activating chromatin modifications and in sperm from the 5'UTR of full-length LINE-1 elements, but were depleted from lamin-associated heterochromatin. Furthermore, analysis of microDNAs from a set of human cancer cell lines revealed lineage-specific patterns of microDNA origins. A survey of microDNAs from chicken cell lines defective in various DNA repair proteins revealed that homologous recombination repair and non-homologous end joining repair pathways are not required for microDNA production. A deletion of the MSH3 protein, involved in DNA mismatch repair, resulted in a significant decrease in microDNA abundance specifically from non-CpG areas of the genome. Thus microDNAs arise as part of normal cellular physiology, either from DNA breaks associated with RNA metabolism or from replication slippage followed by mismatch repair. Circular DNA profiling by high throughput sequencing. Five human, ten mouse and nine chicken samples are analyzed