Evolution of cysteine patterns in the large extracellular loop of tetraspanins from animals, fungi, plants and single-celled eukaryotes

By analyzing the evolution of cysteine patterns in the large extracellular loop (LEL) of tetraspanins across all eukaryotes, we report the following: (1) the origin of the cysteine–cysteine–glycine (CCG) motif in the common ancestor of unikonts (Animalia, fungi and amoebozoa); (2) tracing cysteine motifs on an eukaryotic phylogeny which includes protists, animals and plants match organismal evolution; (3) using this evolutionary approach we have determined some of the cysteines in these proteins that are involved in specific bonds in the LEL. Our study provides a framework to better understand tetraspanin formation, diversification and the evolutionary history of these important proteins.