Variable Lymphocyte Receptors in Jawless Vertebrates: Illuminating the Origin and Early Evolution of Adaptive Immunity

Abstract

Phylogenetic studies of immunity have revealed that about 500 million years ago, two types of recombinatorial adaptive immune systems (AIS) arose in vertebrates. Jawed vertebrates diversify the repertoire of immunoglobulin-domain-based B and T cell antigen receptors mainly through the rearrangement of gene segments and somatic hypermutation, whereas an alternative AIS of jawless vertebrates is based on variable lymphocyte receptors (VLRs) which diversify through recombinatorial usage of leucine-rich repeat (LRR) units. None of the fundamental recognition elements of jawed vertebrates AIS have been found in jawless vertebrates. Despite differences in molecular architecture, the parallel ‘two-arms’ of the AIS evolved within the context of preexisting innate immunity and maintained over a long period of time in jawed and jawless vertebrates, respectively, as a consequence of powerful and enduring evolutionary selection pressure by pathogens and other factors.