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Chromatin-Associated Periodicity in Genetic Variation Downstream of Transcriptional Start Sites
Shin Sasaki 1, Cecilia C. Mello 2, Atsuko Shimada 3, Yoichiro Nakatani 1, Shin-ichi Hashimoto 4, Masako Ogawa 4, Kouji Matsushima 4, Sam Guoping Gu 2, Masahiro Kasahara 1, Budrul Ahsan 1, Atsushi Sasaki 1, Taro Saito 1, Yutaka Suzuki 5, Sumio Sugano 5, Yuji Kohara 6, Hiroyuki Takeda 3, Andrew Fire 2*, Shinichi Morishita 7*
1 Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277–0882, Japan.
2 Departments of Pathology and Genetics, School of Medicine, Stanford University, Stanford, CA 94305–5324, USA.
3 Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113–0033, Japan.
4 Department of Molecular Preventive Medicine, School of Medicine, The University of Tokyo, Tokyo 113–0033, Japan.
5 Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108–8639, Japan.
6 Center for Genetic Resource Information, National Institute of Genetics, Mishima 411–8540, Japan.
7 Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277–0882, Japan.; Bioinformatics Research and Development (BIRD), Japan Science and Technology Agency (JST), Tokyo 102–8666, Japan.
Might DNA sequence variation reflect germline genetic activity and underlying chromatin structure? Using two strains of medaka (Japanese killifish, Oryzias latipes), we compared genomic sequence and mapped ~37.3 million nucleosome cores from medaka Hd-rR blastulae, together with 11,654 representative transcription start sites from six embryonic stages. We observed a ~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 ~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 in molding the DNA sequence on an evolutionary time scale.
