Chromatin-associated periodicity in genetic variation downstream of transcriptional start sites.
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.
Sasaki
Shin
S
Department of Computational Biology, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, 277-0882, Japan.
Mello
Cecilia C
CC
Shimada
Atsuko
A
Nakatani
Yoichiro
Y
Hashimoto
Shin-Ichi
S
Ogawa
Masako
M
Matsushima
Kouji
K
Gu
Sam Guoping
SG
Kasahara
Masahiro
M
Ahsan
Budrul
B
Sasaki
Atsushi
A
Saito
Taro
T
Suzuki
Yutaka
Y
Sugano
Sumio
S
Kohara
Yuji
Y
Takeda
Hiroyuki
H
Fire
Andrew
A
Morishita
Shinichi
S
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
D002843:Chromatin; D009707:Nucleosomes; D004247:DNA