RELATIVE ROLES OF PRIMARY SEQUENCE AND (G+C) PERCENT IN DETERMINING THE HIERARCHY OF FREQUENCIES OF COMPLEMENTARY TRINUCLEOTIDE PAIRS IN DNAS OF DIFFERENT SPECIES

To an approximation Chargaff's rule (%A = %T; %G = %C) applies to sing le-stranded DNA. In long sequences, not only complementary bases but a lso complementary oligonucleotides are present in approximately equal frequencies. This applies to all species studied. However, species usu ally differ in base composition. With the goal of understanding the ev olutionary forces involved, I have compared the frequencies of trinucl eotides in long sequences and their shuffled counterparts. Among the 3 2 complementary trinucleotide pairs there is a hierarchy of frequencie s which is influenced both by base composition (not affected by shuffl ing the order of the bases) and by base order (affected by shuffling). The influence of base order is greatest in DNA of 50% G + C and seems to reflects a more fundamental hierarchy of dinucleotide frequencies. Thus if TpA is at low frequency, all eight TpA-containing trinucleoti des are at low frequency. Mammals and their viruses share similar hier archies, with intra- and intergenomic differences being mainly associa ted with differences in base composition (percentage G + C). E. coli a nd, to a lesser extent, Drosophila melanogaster hierarchies differ fro m mammalian hierarchies; this is associated with differences both in b ase composition and in base order. It is proposed that Chargaff's rule applies to single-stranded DNA because there has been an evolutionary selection pressure favoring mutations that generate complementary oli go-nucleotides in close proximity, thus creating a potential to form s tem-loops. These are dispersed throughout genomes and are rate-limitin g in recombination. Differences in (G + C)% between species would impa ir inter-species recombination by interfering with stem-loop interacti ons.