Extrachromosomal circular DNAs are common copy number variations in eukaryotic cells?

Speaker: Birgitte Regenberg, Section for Cell Biology and Physiology, Department of Biology
Host: Anders Krogh, Section for Computational and RNA Biology

Abstract
Common mutations in all organisms are small nucleotide polymorphisms, insertions and deletions. We have shown that another common genetic alternation exists, extrachromosomal circular DNA (eccDNA). Though eccDNA is previously reported from tumor cells (also known as double minutes) and a few other cell types, eccDNA has so far been given little attention. Even though eccDNA are capable of replicating and integrating into the genome their contribution to genetic variation and evolution of the eukaryotic genomes have largely been deemed irrelevant. To get insight in the genetic variation from eccDNA we developed the first genome-wide screen of eccDNA (Circle-Seq). We identified ~1800 eccDNAs representing 23% of the genome of the yeast, Saccharomyces cerevisiae. These results are surprising as they show that eccDNAs are common mutations that can occur in any part of the genome. We now suggest that eccDNAs have a major impact on genetic variation and evolution of eukaryotic genomes by i) frequent formation of eccDNA through known pathways for DNA repair that lead to ii) transient gene copy number variation through replication and missegregation of eccDNA and iii) stable gene amplifications by chromosomal insertions of eccDNA.