Comparative genomics and evolution of immunoglobulin-encoding loci in tetrapods

The immunoglobulins (Igs or antibodies) as an integral part of the tetrapod adaptive immune response system have evolved toward producing highly diversified molecules that recognize a remarkably large number of different antigens. Antibodies and their respective encoding loci have been shaped by different and often contrasting evolutionary forces, some of which aim to conserve an established pattern or mechanism and others to generate alternative and diversified structural and functional configurations. The genomic organization, gene content, ratio between functional genes and pseudogenes, number and position of recombining genetic elements, and the different levels of divergence present at the germline of the Ig-encoding loci have been evolutionarily shaped and optimized in a lineage- and, in some cases, species-specific mode aiming to increase organismal fitness. Further, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, such as V(D)J recombination, class switch recombination, isotype exclusion, somatic hypermutation, and gene conversion. Diverse tetrapod species, based on their specific germline configurations, use these mechanisms in several different combinations to effectively generate a vast array of distinct antibody types and structures. This chapter summarizes our current knowledge on the Ig-encoding loci in tetrapods and discusses the different evolutionary mechanisms that shaped their diversification.