Previous studies of the dinucleotides flanking both the 5’ and 3’ ends of homooligomer tracts have shown that some flanks are consistently preferred over others (1, 2). In the first preferred group, the homooligomer tracts are flanked by the same nucleotide and/or the complementary nucleotides, e.g., ATAn, TTAn, CCGn, where n=2 - 5. Runs flanked by nucleotides with which they cannot base pair are distinctly disfavored. (In this group An/Tn are flanked by C and/or G; Gn/Cn are flanked by A/T, e.g., CGAn, TnGG, GnAT). The frequencies of runs flanked by A or T, and G or C (“mixed” group) are as expected. Here we seek the origin of this effect and its relevance to protein-DNA interactions. Surprisingly, within the first group, runs flanked by their complements with a pyrimidine-purine junction (e.g., TTAn, CnGG) are greatly preferred. The frequencies of their purine-pyrimidine junction mirror-images is just as expected. This effect, as well as additional ones enumerated below, is seen universally in eukaryotes and in prokaryotes, although it is stronger in the former. Detailed analysis of regulatory regions shows these strong trends, particularly in GC sequences. The potential relationship to DNA conformation and DNA-protein interaction is discussed.