>1.3 billion years ago
||Klos A, Wende E, Wareham KJ, Monk PN. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors. Pharmacol Rev. 2013 Jan65(1):500-43 p.503 left column top paragraphPubMed ID23383423
||Pinto MR, Melillo D, Giacomelli S, Sfyroera G, Lambris JD. Ancient origin of the complement system: emerging invertebrate models. Adv Exp Med Biol. 2007 598: 372-88 DOI: 10.1007/978-0-387-71767-8_26PubMed ID17892225
||P.503 left column top paragraph: "Complement is a vital part of the host defense system, capable of reacting to foreign material and damaged or altered host tissues (Carroll and Sim, 2011). Complement-like genes are present in organisms that diverged more than 1.3 billion years ago (primary source): animals that are incapable of mounting an adaptive immune response possess complement, including the sea-squirt Ciona intestinalis (Pinto et al., 2003) and the “living fossil” horseshoe crab, Carcinoscorpius rotundica (Zarkadis et al., 2001)." Primary source p.373 top paragraph: "A surprising result of these endeavors has been the identification of complement genes
in very ancient species belonging to the phylum Cnidaria, which have been in
existence since about 1,300 million years ago (mya) (Dishaw et al. 2005, Nonaka and Kimura 2006)."