AID/APOBEC-like cytidine deaminases are ancient innate immune mediators in invertebrates

• Published in: Nature communications 2018-05, Vol.9 (1), p.1948-11, Article 1948
• Main Authors: Liu, Mei-Chen, Liao, Wen-Yun, Buckley, Katherine M., Yang, Shu Yuan, Rast, Jonathan P., Fugmann, Sebastian D.
• Format: Article
• Language: English
• Subjects: 38/39; 45/22; 45/23; 45/77; 45/90; 631/181/2806; 631/250/248; Adaptive immunity; Adaptive Immunity - genetics; Amino Acid Sequence; Animals; APOBEC-1 Deaminase - genetics; APOBEC-1 Deaminase - metabolism; Apolipoprotein B; Apolipoproteins; Cytidine deaminase; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Deamination; Digestive system; Divergence; Emergence; Enzymatic activity; Enzymes; Gene expression; Gene Expression Regulation, Enzymologic; Genomes; Humanities and Social Sciences; Humans; Immune response; Immunity; Immunity, Innate - genetics; Immunology; Invertebrates; Invertebrates - classification; Invertebrates - enzymology; Invertebrates - genetics; Lymphocyte receptors; multidisciplinary; Mutation; Nucleic acids; Pathogens; Proteins; Science; Science (multidisciplinary); Sequence Homology, Amino Acid; Species Specificity; Strongylocentrotus purpuratus - enzymology; Strongylocentrotus purpuratus - genetics; Vertebrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-04273-x

In the course of both innate and adaptive immunity, cytidine deaminases within the activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) family modulate immune responses by mutating specific nucleic acid sequences of hosts and pathogens. The evolutionary emergence of these mediators, however, seems to coincide precisely with the emergence of adaptive immunity in vertebrates. Here, we show a family of genes in species within two divergent invertebrate phyla—the echinoderm Strongylocentrotus purpuratus and the brachiopod Lingula anatina —that encode proteins with similarities in amino acid sequence and enzymatic activities to the vertebrate AID/APOBECs. The expression of these invertebrate factors is enriched in tissues undergoing constant, direct interactions with microbes and can be induced upon pathogen challenge. Our findings suggest that AID/APOBEC proteins, and their function in immunity, emerged far earlier than previously thought. Thus, cytidine deamination is probably an ancient innate immune mechanism that predates the protostome/deuterostome divergence. The AID/APOBEC cytidine deaminase family are nucleic acid editors, important for antigen receptor expression and thought to have evolved along with vertebrate adaptive immunity. Here the authors show this family may have evolved prior to adaptive immunity as members with cytidine deaminase activity are present and functional in invertebrate sea urchins and brachiopods.