A biological explanation for the dependence of genome-wide mutation-rate variation on local base context is now becoming clearer. The proportions of G + C relative to A + T—expressed as GC%—is a species-specific DNA character. The frequencies of these single bases correlate with frequencies of corresponding oligonucleotides that are more-sensitive indicators of species specificity. Thus, when k = 3 there are 64 possible trinucleotide sequences and a GC%-rich species has a high frequency of GC-rich 3-mers. Closely related species have similar (...) k-mer patterns. For distantly related species, even if happening to have the same GC% values, k-mer patterns are widely discordant. Conventionally, a base substitution mutation is viewed as a chemical 1-mer phenomenon. However, the selective difference by which the corresponding mutation is scored usually relates to context. Thus, an A to U codon mutation in sickle cell anemia, rather than attracting an anticodon in a structural loop of glutamate tRNA, pairs with the more complementary anticodon loop of valine tRNA. Likewise, a recent statistical analysis of genome-wide mutation-rate variation supports the view that a failure of discordant DNA loops to pair at meiosis can initiate and/or sustain the speciation process. Such disharmony among base patterns may have unknowingly been hinted at by geneticist William Bateson who invoked a music metaphor when considering speciation mechanisms. (shrink)