title: Evolution of TNF-induced apoptosis reveals 550 My of functional conservation.
abstract: The Precambrian explosion led to the rapid appearance of most major animal phyla alive today. It has been argued that the complexity of life has steadily increased since that event. Here we challenge this hypothesis through the characterization of apoptosis in reef-building corals, representatives of some of the earliest animals. Bioinformatic analysis reveals that all of the major components of the death receptor pathway are present in coral with high-predicted structural conservation with Homo sapiens. The TNF receptor-ligand superfamilies (TNFRSF/TNFSF) are central mediators of the death receptor pathway, and the predicted proteome of Acropora digitifera contains more putative coral TNFRSF members than any organism described thus far, including humans. This high abundance of TNFRSF members, as well as the predicted structural conservation of other death receptor signaling proteins, led us to wonder what would happen if corals were exposed to a member of the human TNFSF (HuTNFα). HuTNFα was found to bind directly to coral cells, increase caspase activity, cause apoptotic blebbing and cell death, and finally induce coral bleaching. Next, immortalized human T cells (Jurkats) expressing a functional death receptor pathway (WT) and a corresponding Fas-associated death domain protein (FADD) KO cell line were exposed to a coral TNFSF member (AdTNF1) identified and purified here. AdTNF1 treatment resulted in significantly higher cell death (P < 0.0001) in WT Jurkats compared with the corresponding FADD KO, demonstrating that coral AdTNF1 activates the H. sapiens death receptor pathway. Taken together, these data show remarkable conservation of the TNF-induced apoptotic response representing 550 My of functional conservation.
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182; steven.quistad@gmail.com.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Quistad
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182;The Cedars-Sinai Heart Institute, Los Angeles, CA 90048; and.
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Stotland
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182;Marine Biology Research Division, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Katie L
authors.initials: KL
authors.lastname: Barott
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182;
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Smurthwaite
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182;
authors.forename: Brett Jameson
authors.initials: BJ
authors.lastname: Hilton
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182;
authors.forename: Juris A
authors.initials: JA
authors.lastname: Grasis
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182;
authors.forename: Roland
authors.initials: R
authors.lastname: Wolkowicz
authors.affiliation: Department of Biology, San Diego State University, San Diego, CA 92182;
authors.forename: Forest L
authors.initials: FL
authors.lastname: Rohwer
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics* / Q000276:immunology; D000818:Animals; D037421:Anthozoa / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D005075:Biological Evolution; D002478:Cells, Cultured; D019295:Computational Biology; D015180:Electrophoresis, Gel, Two-Dimensional; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism; D005434:Flow Cytometry; D055786:Gene Knockout Techniques; D006801:Humans; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008856:Microscopy, Fluorescence; D053218:Receptors, Death Domain / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000494:pharmacology
chemical_list: C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D053218:Receptors, Death Domain; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha
keywords: Cnidarians; climate change; cytokines; evolution immunity; invertebrate immunity