Evolution of TNF-induced apoptosis reveals 550 My of functional conservation

The TNF receptor-ligand superfamily is a central mediator of apoptosis or programmed cell death. Here we show that TNF-induced apoptosis has been functionally maintained for more than half a billion years of evolution. In response to human TNFα, coral cells underwent the classical stages of apoptosis including cellular blebbing, caspase activation, and eventual cell death. Next, the reciprocal experiment showed that coral TNF kills human cells through direct interaction with the death receptor pathway. In addition, corals were found to possess more putative TNF receptors than any organism previously described, including humans. This work provides important insight into the general evolution of apoptosis and demonstrates remarkable conservation of the TNF apoptotic response.