The Janus (dual) model of immunoglobulin isotype evolution: Conservation and plasticity are the defining paradigms.

The study of antibodies in jawed vertebrates (gnathostomes) provides every immunologist with a bird's eye view of how human immunoglobulins (Igs) came into existence and subsequently evolved into their present forms. It is a fascinating Darwinian history of conservation on the one hand and flexibility on the other, exemplified by the Ig heavy chain (H) isotypes IgM and IgD/W, respectively. The cartilaginous fish (e.g., sharks) Igs provide a glimpse of "how everything got off the ground," while the amphibians (e.g., the model Xenopus) reveal how the adaptive immune system made an about face with the emergence of Ig isotype switching and IgG-like structure/function. The evolution of mucosal Igs is a captivating account of malleability, convergence, and conservation, and a call to arms for future study! In between there are spellbinding chronicles of antibody evolution in each class of vertebrates and rather incredible stories of how antibodies can adapt to occupy niches, for example, single-domain variable regions, cold-adapted Igs, convergent mechanisms to dampen antibody function, provision of mucosal defense, and many more. The purpose here is not to provide an encyclopedic examination of antibody evolution, but rather to hit the high points and entice readers to appreciate how things "came to be."