AID/APOBEC-Like Cytosine Deaminases Are Important Mediators of VLR-Based Adaptive Immunity in Cyclmtomata

Abstract

Jawless vertebrates have been studied for the evolutionary origin of adaptive immunity because of their pivotal position in chordate phylogeny. However, the convergent evolution of adaptive immunity in vertebrates is lacking. This study evaluates the similarity of adaptive immune mechanisms between jawless and jawed vertebrates using lamprey cytidine deaminase (CDA). We identified the ancestral gene Lr-CDAs of the AID/APOBEC deaminase family and evaluated its biological function in vivo. Lr-CDA1 deletion affected the assembly of three types of variable lymphocyte receptors (VLRs). We identified a switch-like region in lamprey gVLRs bound to Lr-CDAs, which upon repression, downregulated VLRB expression. Overall, we propose that lampreys have an early form of class switch recombination (CSR) that is mediated by Lr-CDAs and acts on gVLRs, affecting the assembly, maturation, and diversity regulation of VLR genes in Lethenteron reissneri. This CSR process in lampreys is linked to tumorigenesis and chromosomal translocation markers via Lr-CDAs.