title: Extrachromosomal circular DNA is common in yeast.
abstract: Examples of extrachromosomal circular DNAs (eccDNAs) are found in many organisms, but their impact on genetic variation at the genome scale has not been investigated. We mapped 1,756 eccDNAs in the Saccharomyces cerevisiae genome using Circle-Seq, a highly sensitive eccDNA purification method. Yeast eccDNAs ranged from an arbitrary lower limit of 1 kb up to 38 kb and covered 23% of the genome, representing thousands of genes. EccDNA arose both from genomic regions with repetitive sequences ≥ 15 bases long and from regions with short or no repetitive sequences. Some eccDNAs were identified in several yeast populations. These eccDNAs contained ribosomal genes, transposon remnants, and tandemly repeated genes (HXT6/7, ENA1/2/5, and CUP1-1/-2) that were generally enriched on eccDNAs. EccDNAs seemed to be replicated and 80% contained consensus sequences for autonomous replication origins that could explain their maintenance. Our data suggest that eccDNAs are common in S. cerevisiae, where they might contribute substantially to genetic variation and evolution.
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Henrik D
authors.initials: HD
authors.lastname: Møller
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544;
authors.forename: Lance
authors.initials: L
authors.lastname: Parsons
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Tue S
authors.initials: TS
authors.lastname: Jørgensen
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544; Calico Life Sciences LLC, South San Francisco, CA 94080 botstein@princeton.edu BRegenberg@bio.ku.dk.
authors.forename: David
authors.initials: D
authors.lastname: Botstein
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen N, Denmark; botstein@princeton.edu BRegenberg@bio.ku.dk.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Regenberg
mesh_terms: D001483:Base Sequence; D004270:DNA, Circular / Q000235:genetics* / Q000302:isolation & purification; D004271:DNA, Fungal / Q000235:genetics* / Q000302:isolation & purification; D019143:Evolution, Molecular; D005111:Extrachromosomal Inheritance; D014644:Genetic Variation; D016681:Genome, Fungal; D008957:Models, Genetic; D009154:Mutation; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000235:genetics*
chemical_list: D004270:DNA, Circular; D004271:DNA, Fungal
keywords: DNA replication origins; chromosomal instability; circular DNA; gene deletion; homologous recombination