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. evolution immunity | cytokines | Cnidarians | climate change | invertebrate immunity

Evolutionarily conserved primary TNF sequences relate to its primitive functions in cell death induction

“…TNF has evolved to be very important in both innate and adaptive immunity. As Quistat et al have reported, the origin of TNF can be dated back to 550 million years ago, well before the divergence of vertebrates and invertebrates (Quistad et al, 2014). Our data suggest that the highly conserved regions of TNF structure are those that play a role in cell toxicity, and it is possible that this was originally the sole molecular function.…”

“…TNF is thought to have emerged during the Precambrian era (more than 550 million years ago) before the animal phyla started to evolve (Quistad et al, 2014). The fact that certain functions of TNF -e.g.…”

Cacidases: caspases can cleave after aspartate, glutamate and phosphoserine residues

“…35 Indeed, initial in vitro tests of human and other species' apoptotic and nonapoptotic caspase activities for Ac-DEVE-AFC have indicated broad glutamic acid activity (Supplementary Table 4). 36 In addition, in silico caspase substrate algorithms have predicted, but not empirically confirmed, the ability for caspases to cleave P1 glutamate substrates. 37,38 Probably the bestcharacterized functional example is for DRONC, a Drosophila caspase, that cleaves itself during activation after glutamate.…”

The cell specificity of gene expression in the response to heat stress in corals

“…Additionally, FosB can be active on its own and has been linked to functions in the extracellular matrix control of smooth muscle cells (Ramachandran et al, 2011). TNFR41 is part of the TNFR family, which was previously found to be highly upregulated in response to heat in corals (Barshis et al, 2013;Quistad et al, 2013Quistad et al, , 2014Quistad and Traylor-Knowles, 2016;Traylor-Knowles and Palumbi, 2014), and its role in other organisms includes activating signaling pathways leading to apoptosis or to proliferation of cells (Aggarwal, 2003;Cabal-Hierro and Lazo, 2012;Gaur and Aggarwal, 2003;MacEwan, 2002). Fig.…”

“…Additionally, module 1 was identified as being highly enriched for a large number of general stress response-like genes, including tumor necrosis factor receptor (TNFR) genes (Rose et al, 2015). The TNFR gene family has recently been identified as having significant upregulation in corals exposed to heat stress but the actual function and localization of this gene response within the coral animal is still not understood (Barshis et al, 2013;Quistad and Traylor-Knowles, 2016;Quistad et al, 2014). Throughout the continuation of this article, we will refer to module 1 as the 'stress response module' and module 12 as the 'bleaching module'.…”