title: Chromatin-associated periodicity in genetic variation downstream of transcriptional start sites.
abstract: Might DNA sequence variation reflect germline genetic activity and underlying chromatin structure? We investigated this question using medaka (Japanese killifish, Oryzias latipes), by comparing the genomic sequences of two strains (Hd-rR and HNI) and by mapping approximately 37.3 million nucleosome cores from Hd-rR blastulae and 11,654 representative transcription start sites from six embryonic stages. We observed a distinctive approximately 200-base pair (bp) periodic pattern of genetic variation downstream of transcription start sites; the rate of insertions and deletions longer than 1 bp peaked at positions of approximately +200, +400, and +600 bp, whereas the point mutation rate showed corresponding valleys. This approximately 200-bp periodicity was correlated with the chromatin structure, with nucleosome occupancy minimized at positions 0, +200, +400, and +600 bp. These data exemplify the potential for genetic activity (transcription) and chromatin structure to contribute to molding the DNA sequence on an evolutionary time scale.
authors.affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, 277-0882, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Sasaki
authors.forename: Cecilia C
authors.initials: CC
authors.lastname: Mello
authors.forename: Atsuko
authors.initials: A
authors.lastname: Shimada
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Masako
authors.initials: M
authors.lastname: Ogawa
authors.forename: Kouji
authors.initials: K
authors.lastname: Matsushima
authors.forename: Sam Guoping
authors.initials: SG
authors.lastname: Gu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kasahara
authors.forename: Budrul
authors.initials: B
authors.lastname: Ahsan
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sasaki
authors.forename: Taro
authors.initials: T
authors.lastname: Saito
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Sumio
authors.initials: S
authors.lastname: Sugano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kohara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeda
authors.forename: Andrew
authors.initials: A
authors.lastname: Fire
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morishita
mesh_terms: D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002843:Chromatin / Q000502:physiology* / Q000648:ultrastructure; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D004260:DNA Repair; D014644:Genetic Variation; D016678:Genome; D054643:INDEL Mutation; D016296:Mutagenesis; D009154:Mutation; D009707:Nucleosomes / Q000502:physiology* / Q000648:ultrastructure; D009990:Oryzias / Q000196:embryology / Q000235:genetics*; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D009707:Nucleosomes; D004247:DNA