Hypothetical evolutionary models of the variable lymphocyte receptor genes in jawless vertebrates

Abstract

Abstract Both humoral and cellular arms of an adaptive immune system are common to jawed and jawless vertebrates. However, whereas antigen recognition in the jawed vertebrates is mediated by immunoglobulin domain-based B cell receptors and T cell receptors, antigen recognition in jawless vertebrates is mediated by leucine-rich repeat (LRR) sequences in variable lymphocyte receptors (VLRs). Three types of VLR genes (VLRA, VLRB and VLRC) have been characterized in the extant jawless vertebrates, lampreys and hagfishes. VLRA- and VLRC-producing cells are T cell-like, while VLRB-producing cells are B cell-like. The VLRs are assembled by copying neighboring LRR sequences into the incomplete germline genes. In searching for the evolutionary origin of the VLRs we identified hypothetical VLR-like progenitors in amphioxus and tunicates (VLRPs). Molecular cladistics markers and phylogenetic analysis suggest the VLRPs are structurally more similar than other ancestral candidates to assembled VLRs. Based on our further analysis we propose alternative models for the origin of VLRs: (A) Among the VLRs, VLRB is most similar to the ancestral state and two subsequent duplication events gave rise to VLRC and VLRA-like genes; each of the three ancestral VLR genes in a common jawless vertebrate ancestor was then modified by cut and paste transposition of the internal DNA region encoding multiple LRR modules. (B) A cut and paste transposition event in an ancestral VLRB-like gene was followed by sequential duplication events which gave rise to VLRC and VLRA. In both models, subsequent duplications and fragmentations have generated a large array of genomic donor cassettes. Thus, after the emergence of the three VLR loci, each has undergone independent evolution.