Characterization of Evolutionarily Conserved Aid/Apobec-Like Dna/Rna Deaminases as Mediators of Invertebrate Immunity

Cytidine deaminases of the AID/APOBEC family play critical roles in vertebrate immune systems. Their ability to mutate ssDNA and RNA transcripts is utilized by the adaptive immune system to diversify immunoglobulin genes and by the innate immune system to prevent the integration of retroviruses and retrotransposons into the genome of the vertebrate hosts. These mutator enzymes are tightly controlled as their activity contributes to genomic instability and tumorigenesis when directed against non-target regions of the genome or transcriptome. Their emergence during evolution as immune mediators is concurrent with the appearance of adaptive immunity, and surprisingly no clear homolog of AID/APOBEC has been described in any invertebrate to date. We recently discovered putative AID/APOBEC-like mRNA in a Strongylocentrotus purpuratus (purple sea urchin) immune cell transcriptome and in the genome of Lingula anatina, a brachiopod, strongly suggesting an unexpected potential role of such factors in invertebrate immunity. This proposal is now aimed at (1) identifying novel members of this gene family in the invertebrate kingdom, (2) characterizing their enzymatic properties, and (3) discovering their role in invertebrate host defenses. Comparing the properties and roles of invertebrate and vertebrate deaminases has the potential to reveal fundamental aspects of deaminase mediated immune responses and to discover access points to regulate the activity of relevant deaminases in the context of human diseases.

Project ID:PC10703-0220
External Project ID:MOST106-2320-B182-011