Chromatin-Associated Periodicity in Genetic Variation Downstream of Transcriptional Start Sites

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.