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. 2016 Jul 18;2:16058. doi: 10.1038/cddiscovery.2016.58

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Copyright © 2016 The Author(s)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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Hypothesis for the origin of TNFRs. The CRD existed in the last common eukaryotic ancestor (LECA) while the TNFR-specific DD emerged before the last common metazoan ancestor (LCMA). Following a fusion event between a CRD and DD, the primordial TNFR involved in apoptosis was formed.