Caught in the act of triplication: TNF superfamily

Abstract

ABSTRACTThe first sighting of a homolog of tumor necrosis factor in invertebrates,DmEiger, was in 2002 fromDrosophila melanogasterwith a potential role in apoptosis. More recently, the presence of a Eiger homolog along with homologs of all the genes from TNF-TNFR signaling pathway in a malaria vector, suggests the existence of this modality of signaling since 700 mya. Furthermore, a comparison of the crystal structure configuration of DmEiger bound to its receptor DmGrnd and that of HuTNF-HuTNFR complex predates the ligand-receptor configuration to 700 mya. In human, there are 29 paralogs of TNF superfamily with 19 receptor genes suggesting active evolution of TNF-TNFR system within species. The recent explosion in proteomes of thousands of organisms from species covering every branch of Metazoa provides a rich source to study the mode of expansion of this system within species. Here, we have studied 148 near-complete proteomes under each major phylum and report presence/absence of TNF-TNFR homologs across the animal kingdom. The system is lost in Nematoda, Tardigrada, Chelicerates, and parasitic species under Platyhelminthes. By interrogating the topologies of genes containing multiple homologs of TNF and TNFR domains in species under Cnidaria, Mollusca, Crustacea, and Annelida, we hypothesize that heterotrimeric ligand oligomerization for signaling may have predated function expansion by homotrimerization followed by receptor evolution in a yin-yang manner.