Editing Tumor necrosis factor (section)

== Evolution ==
The TNF and lymphotoxin-α genes are believed to be descended from a common ancestor gene that developed early in vertebrate evolution, before the [[Agnatha]] and [[Gnathostomata]] split. This ancestor gene was dropped from the Agnatha ancestor but persisted in the Gnathostomata ancestor. During the evolution of gnathostomes, this ancestor gene was duplicated into the TNF and lymphotoxin-α genes.<ref name="pmid33210144">{{cite journal | vauthors = Marín I | title = Tumor Necrosis Factor Superfamily: Ancestral Functions and Remodeling in Early Vertebrate Evolution | journal =  Genome Biology and Evolution| volume = 12 | issue = 11 | pages = 2074–2092 | date = November 2020 | pmid = 33210144 | pmc = 7674686 | doi = 10.1093/gbe/evaa140  | doi-access = free }}</ref> Thus, while the ancestor gene is found across a variety of gnathostome species, only a subset of gnathostome species contain a TNF gene. Some fish species, such as [[Danio]], have been found to contain duplicates of the TNF gene.<ref name="pmid33210144"/>

The TNF gene is very similar among mammals, ranging from 233 to 235 amino acids.<ref name="TumorNecrosisFactorsDCI">{{cite journal | vauthors = Goetz FW, Planas JV, MacKenzie SI | title = Tumor necrosis factors | journal = Development & Comparative Immunology | volume = 28 | issue = 5 | pages = 487–497 | date = May 2004 | doi = 10.1016/j.dci.2003.09.008 | pmid = 15062645 }}</ref> The TNF proximal promoter region is also highly conserved among mammals, and nearly identical among [[higher primates]].<ref name="TNFPathophysiology"/> The similarity of the TNF gene among fish is lower, ranging from 226 to 256 amino acids. Like mammalian TNF, the fish TNF gene has been shown to be stimulated in [[macrophages]] by [[antigens]].<ref name="TumorNecrosisFactorsDCI"/> All TNF genes have a highly conserved [[C-terminal]] module known as the TNF homology domain, due to its important role in binding TNF to its receptors.<ref name="pmid33210144"/>