AID/APOBEC -LIKE CYTIDINE DEAMINASES ARE ANCIENT INNATE IMMUNE MEDIATORS IN INVERTEBRATES
Mei-Chen Liu, Chang Gung University
Mei-Chen Liu1, Wen-Yun Liao1, Katherine M Buckley4,5,6, Shu Yuan Yang1,2,7, Jonathan P. Rast4,5,6, Sebastian D. Fugmann3,8,9
1. Department of Biomedical Sciences, 2. Division of Biochemistry, Molecular and Cellular Biology, Graduate Institute of Biomedical Sciences, 3. Division of Microbiology, Graduate Institute of Biomedical Sciences, Chang Gung University, Tao-Yuan, Taiwan
4. Biological Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada
5. Department of Medical Biophysics, 6. Department of Immunology, University of Toronto, Toronto, Ontario, Canada
7. Department Of Pathology, 8. Department of General Surgery, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan
9. Chang Gung Immunology Consortium, Chang Gung Memorial Hospital and Chang Gung University, Kwei-Shan District, Tao-Yuan, Taiwan
Vertebrate immune systems utilize targeted alterations of nucleotide sequences within both host and pathogen as powerful defense mechanisms. During innate and adaptive immune responses, activation induced cytidine deaminase (AID)/apolipoprotein B editing complex (APOBEC) cytidine deaminases initiate such processes. Their appearance in evolution coincides precisely with the emergence of adaptive immunity in vertebrates. Here we now report the discovery of novel genes in two invertebrates, Strongylocentrotus purpuratus and Lingula anatina, encoding proteins with striking similarities of amino acid sequence and enzymatic activities to vertebrate AID/APOBECs. Their expression is highest in tissues with constant intimate interactions with microbes, and can be induced upon pathogen challenge. Our findings strongly suggest that cytidine deamination represents an ancient innate immune mechanism dating back to protostomes.
This work was supported by Chang Gung Memorial Hospital grants (CMRPD1C0242,
CMRPD1F0421, CORPD1F0051) and a Ministry of Science and Technology grant (102-2320-
B-182 -001 -MY3) to SDF.