Evolutionary analyses of caspase-8 and its paralogs: Deep origins of the apoptotic signaling pathways

Although Caenorhabditis and Drosophila proved invaluable in unraveling the molecular mechanisms of apoptosis, it is now clear that these animals are of limited value for understanding the evolution of apoptotic systems. Whereas data from these invertebrates led to the assumption that the extrinsic apoptotic pathway is restricted to vertebrates, recent data from cnidarians and sponges indicate that this pathway predates bilaterian origins. Here we review the phylogenetic distribution of caspase-8, the initiator caspase of the extrinsic apoptotic pathway, its paralogs and other components of the network. The ancestral caspase-8 gave rise to four paralogs early in vertebrate evolution, and these have been maintained in many tetrapods. However, eutherians have lost caspase-18 and myomorph rodents have lost caspase-10, these losses suggesting functional redundancy amongst caspase-8 paralogs. The apoptotic network of the eumetazoan ancestor appears to have been complex and vertebrate like, and is only now being revealed by studying simple animals.