Abstract
The evolution of the tumor necrosis factor/tumor necrosis factor receptor superfamily (TNF/TNFR) is complicated and not well understood. To date, most TNFR studies have focused on vertebrate models leaving the role of TNFRs in invertebrates largely unexplored. The evolution of important cellular processes including stress response, apoptosis, development, and inflammation will be better understood by examining the TNF/TNFR superfamily in ancient invertebrate phyla. How widespread is this gene family within the evolutionary tree of life and is there evidence for similar function in invertebrates? A first step is to identify the presence or absence of these genes within basal metazoan taxa using the signature cysteine-rich domain (CRD) of the TNFR superfamily. In this perspective, we will start by examining what is currently known about the function of TNFRs in invertebrates. Then, we will assess the role of TNFRs in apoptosis and explore the origins of the domains found in TNFRs including the death domain (DD) and CRD. Finally, we will examine the phylogenetic relationship between TNFRs containing DDs identified to date. From these data, we propose a model for a Precambrian origin of TNFRs and their functional role in apoptosis.
Highlights
The evolution of the tumor necrosis factor/tumor necrosis factor receptor superfamily (TNF/TNFR) is complicated and not well understood
We will assess the role of TNFRs in apoptosis and explore the origins of the domains found in TNFRs including the death domain (DD) and cysteine-rich domain (CRD)
We propose that the CRD emerged in the last common eukaryotic ancestor followed by a fusion event with a DD during the last common metazoan ancestor resulting in the first TNFR involved in apoptosis (Figure 2)
Summary
The evolution of the tumor necrosis factor/tumor necrosis factor receptor superfamily (TNF/TNFR) is complicated and not well understood. The evolution of important cellular processes including stress response, apoptosis, development, and inflammation will be better understood by examining the TNF/TNFR superfamily in ancient invertebrate phyla How widespread is this gene family within the evolutionary tree of life and is there evidence for similar function in invertebrates? Invertebrate members of the phyla chordata (e.g., tunicates, hagfish, and cephalochordates) are considered to be the most closely related to humans, and have been the focus of many studies on diversity of the innate immune system and its divergence from the adaptive immune system.[10] For example, in the tunicates, Ciona savignyi and Ciona intestinalis, TNF-α was upregulated in hemocytes in response to a lipopolysaccharide challenge and was primarily expressed in inflammatory granulocytes that occurred at the area of inflammation.[11] The lancelet fish, Amphioxus, has an extensive repertoire of TNF/TNFRs present in its genome.[12] In response to an lipopolysaccharide immune challenge, moderate upregulation of TNF and TNFR occurred and it was a dynamic response depending on the homolog From these data, it was concluded that TNF and TNFR could be important in. The role of the Eiger/Wegen system in immunity is very intricate, where tolerance phenotypes for intracellular Gram-
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