title: GC skew and mitochondrial origins of replication.
abstract: The comprehensive understanding of mitochondrial genome evolution requires a detailed mechanistic picture of mitogenomic replication. Despite many previous efforts it has remained a non-trivial problem to determine the origins of replication and trace their fate across rearrangements of the gene order even in the small genomes of animal mitochondria. We elaborate here on the observation that the GC skew is correlated with the distance from the replication origins. This effect has been explained as a consequence of the standard model of mitochondrial DNA replication, i.e. the strand displacement model. According to this model chemical damage accumulates proportional to the duration that DNA is exposed in single-stranded form during replication (Dssh) which depends on the relative position with respect to the replication origins. Based on this model we developed a computational method to infer the positions of both the heavy strand and the light strand origin from nucleotide skew data. In a comprehensive survey of deuterostome mitochondria we infer conserved replication origins for the vast majority of vertebrates and cephalochordates. Deviations from the consensus picture are presumably associated with genome rearrangements.
authors.affiliation: Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, Universität Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Germany; Doctoral School of Science and Technology, AZM Center for Biotechnology Research, Lebanese University, Tripoli, Lebanon. Electronic address: abdullah@bioinf.uni-leipzig.de.
authors.forename: Abdullah H
authors.initials: AH
authors.lastname: Sahyoun
authors.affiliation: Parallel Computing and Complex Systems Group, Department of Computer Science, University of Leipzig, Augustusplatz 10, D-04109 Leipzig, Germany. Electronic address: bernt@informatik.uni-leipzig.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bernt
authors.affiliation: Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, Universität Leipzig, Härtelstraße 16-18, D-04107 Leipzig, Germany; Max-Planck-Institute for Mathematics in the Sciences, Inselstraße 22, D-04103 Leipzig, Germany; Fraunhofer Institut für Zelltherapie und Immunologie, Perlickstraße 1, D-04103 Leipzig, Germany; Department of Theoretical Chemistry, University of Vienna, Währingerstraße 17, A-1090 Wien, Austria; Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, DK-1870 Frederiksberg, Denmark; Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, NM 87501, USA. Electronic address: studla@bioinf.uni-leipzig.de.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.affiliation: Doctoral School of Science and Technology, AZM Center for Biotechnology Research, Lebanese University, Tripoli, Lebanon. Electronic address: ktout@ul.edu.lb.
authors.forename: Kifah
authors.initials: K
authors.lastname: Tout
mesh_terms: D000818:Animals; D001482:Base Composition; D019295:Computational Biology / Q000379:methods; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D018741:Replication Origin; D014714:Vertebrates
chemical_list: D004272:DNA, Mitochondrial
keywords: Chordata; GC-skew; Mitochondria; Replication origins