Going Adaptive The Saga of Antibodies

Because of their extreme importance to human health, we probably know more about the structure and function of antibodies than practically any other molecule. Despite all the knowledge that has been accrued in the understanding of antibodies, modern approaches, especially comparative genomics, continue to yield novel findings regarding their underlying biology and evolution. In this review, we describe recent research that led to these revelations, and discuss the broad evolutionary implications of these findings. We have restricted our discussion to three vignettes. Considerable attention has been paid to the recent discovery that the teleost IgH locus is highly similar in organization to the Tcra-Tcrd locus, implicating an evolutionary common ancestor and parallels between the functions of B and T cells during development. Second, we discuss how a new type of antibody, recently discovered in jawless vertebrates, composed not of immunoglobulins but leucine-rich repeats, sheds new light on the overall forces driving evolution of all adaptive antigen receptors. Lastly, we discuss how accumulation of genomic sequences of various human subpopulations leads to better understanding of the directionality of antibody evolution. There is always more to learn from the unfolding saga of antibodies.