Background Several millions single nucleotide polymorphisms (SNPs) have already been collected and deposited in public databases and these are important resources not only for use as markers to identify disease-associated genes, but also to understand the mechanisms that underlie the genome diversification. Results A spectrum analysis of SNP density distribution in the genomic regions around transcription start sites (TSSs) revealed a remarkable periodicity of 146 nucleotides. This periodicity was observed in the regions that were associated with CpG islands (CGIs), but not in the regions without CpG islands (nonCGIs). An analysis of the sequence divergence of the same genomic regions between humans and chimpanzees also revealed a similar periodical pattern in CGI. The occurrences of any mono- or di-nucleotide sequences in these regions did not reveal such a periodicity, thus indicating that an interpretation of this periodicity solely based on the sequence-dependent susceptibility to mutation is highly unlikely. Conclusion The periodical patterns of nucleotide variability suggest the location of nucleosomes that are phased at TSS, and can be viewed as the genetic footprint of the chromatin state that has been maintained throughout mammalian evolutionary history. The results suggest the possible involvement of the nucleosome structure in the promoter function, and also a fundamental functional/structural difference between the two promoter classes, i.e., those with and without CGIs.