The Origins of Aid/Apobec-Like Deaminases in Innate and Adaptive Immunity

The AID/APOBEC family of polynucleotide cytidine deaminases is essential for efficient vertebrate immune responses. The distinct genetic programs mediating the diversification of immunoglobulin genes, the suppression of viruses, retroviruses, and retrotransposons, all share the mutation of DNA and RNA transcripts by these enzymes as a common mechanism. These mutagenic activities are tightly regulated and directed towards their cognate DNA and RNA targets to prevent undesired DNA lesion leading to genomic instability and tumorigenesis. Despite the innate immune functions of AID/APOBECs, their emergence during metazoan evolution is concurrent with the appearance of adaptive immunity in vertebrates. We recently discovered the first invertebrate members of theAID/APOBEC family in Strongylocentrotus purpuratus (purple sea urchin) and Lingula anatina, a brachiopod. A preliminary characterization of some of these factors suggested an unexpected potential role of such factors in invertebrate immunity. This proposal is now aimed at (1)characterizing their enzymatic properties, (2) discovering their targets in invertebrates, and (3) identifying their role in invertebrate immunity. Comparing the properties and roles of invertebrate and vertebrate deaminases has the potential to reveal conserved concepts of deaminase mediated immune responses and this may provide insight as to how modulate the activity of these enzymes in the context of human diseases.

Project ID:PC10707-0173
External Project ID:MOST107-2320-B182-002