" The substrates within each CDR that are frequently seen mutated are defined as “hotspots”. They are described by preferences for purines, rather than pyrimidines, as well as for particular codons, or codon motifs within the sequence. The fact that mutation in a hotspot can create or delete other hotspots indicates a higher order structure to the mutation process than that which is currently observable.
McKay Brown, Mary Stenzel-Poore, Susan Stevens, Sophia K. Kondoleon, James Ng, Hans Peter Bachinger, and Marvin B. Rittenberg. Immunologic memory to phosphocholine keyhole limpet hemocyanin. Journal of Immunology, 148(2):339–346, January 1992. "

― , Evolution as Computation: Dimacs Workshop, Princeton, January 1999