title: Substitutions of short heterologous DNA segments of intragenomic or extragenomic origins produce clustered genomic polymorphisms.
abstract: In a screen for unexplained mutation events we identified a previously unrecognized mechanism generating clustered DNA polymorphisms such as microindels and cumulative SNPs. The mechanism, short-patch double illegitimate recombination (SPDIR), facilitates short single-stranded DNA molecules to invade and replace genomic DNA through two joint illegitimate recombination events. SPDIR is controlled by key components of the cellular genome maintenance machinery in the gram-negative bacterium Acinetobacter baylyi. The source DNA is primarily intragenomic but can also be acquired through horizontal gene transfer. The DNA replacements are nonreciprocal and locus independent. Bioinformatic approaches reveal occurrence of SPDIR events in the gram-positive human pathogen Streptococcus pneumoniae and in the human genome.
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, The Arctic University of Norway, 9037 Tromsø, Norway; klaus.harms@spdir.net ewillerslev@snm.ku.dk paal.johnsen@uit.no.|Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen K, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Harms
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, The Arctic University of Norway, 9037 Tromsø, Norway.
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Lunnan
authors.affiliation: Genomic Microbiology, Institute of Microbiology, Christian-Albrechts-Universität zu Kiel, 24118 Kiel, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Hülter
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen K, Denmark.
authors.forename: Tobias
authors.initials: T
authors.lastname: Mourier
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen K, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Vinner
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115.
authors.forename: Cheryl P
authors.initials: CP
authors.lastname: Andam
authors.affiliation: Helsinki Institute for Information Technology, Department of Computer Science, Aalto University, FIN-00076 Aalto, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Marttinen
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen K, Denmark.|Department of Microbiological Diagnostics and Virology, Statens Serum Institut, 2300 Copenhagen S, Denmark.
authors.forename: Helena
authors.initials: H
authors.lastname: Fridholm
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen K, Denmark.
authors.forename: Anders Johannes
authors.initials: AJ
authors.lastname: Hansen
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115.
authors.forename: William P
authors.initials: WP
authors.lastname: Hanage
authors.affiliation: Department of Life Sciences and Health, Oslo and Akershus University College of Applied Sciences, 0130 Oslo, Norway.|GenØk-Center for Biosafety, 9294 Tromsø, Norway.
authors.forename: Kaare Magne
authors.initials: KM
authors.lastname: Nielsen
authors.affiliation: Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, 1350 Copenhagen K, Denmark; klaus.harms@spdir.net ewillerslev@snm.ku.dk paal.johnsen@uit.no.
authors.forename: Eske
authors.initials: E
authors.lastname: Willerslev
authors.affiliation: Department of Pharmacy, Faculty of Health Sciences, The Arctic University of Norway, 9037 Tromsø, Norway; klaus.harms@spdir.net ewillerslev@snm.ku.dk paal.johnsen@uit.no.
authors.forename: Pål Jarle
authors.initials: PJ
authors.lastname: Johnsen
mesh_terms: D000150:Acinetobacter / Q000235:genetics; D000483:Alleles; D019295:Computational Biology / Q000379:methods; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000235:genetics; D017353:Gene Deletion; D022761:Gene Transfer, Horizontal; D015894:Genome, Human; D023281:Genomics; D005838:Genotype; D006801:Humans; D009153:Mutagens; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000235:genetics*
chemical_list: D004277:DNA, Single-Stranded; D009153:Mutagens; D004247:DNA
keywords: illegitimate recombination; microindels; mutation