 Highlighting the importance of directed mutagenesis and programmed gene rearrangements in evolution, these studies potentially revise dominant theories of adaptation. Indeed, such genetic changes operate in the vertebrate adaptive immune system: The first exposure of antigen leads to selection of a diverse population of lymphocytes, each carrying antigen receptors of a single specificity with varying degrees of affinity for the newly introduced antigen; the stochastic but coordinated assembly of gene segments determines receptor binding fitness (Tonegawa, et al. 1974; Podolsky and Tauber 1997). Higher degrees of specificity arise through a class of lymphocytes (B cells), whose activation by a specific antigen induces further variation and selection. This mechanism exhibits hypermutation, in which rearranged antigen receptor genes are subjected to scattered, random point mutations to permit rapid selection of a cell variant with an enhanced binding fitness. As the process of hypermutation acts on pre-selected cells to improve adaptive fit of their receptors, its outcomes are partially biased, failing to exactly fit into the Neo-Darwinian scheme (cf. Dobzhansky 1970). Thus, in the course of antigenic exposure, the population of lymphocytes that recognize a newly introduced antigen collectively generates an increasingly effective pool of responsive cells by fine-tuning the specificity of immune receptors, a process that exemplifies non-random selection and adaptation (Simon, Hollander, and McMichael 2015).