Phylogenetic analysis of the homologous proteins of the terminal complement complex supports the emergence of C6 and C7 followed by C8 and C9

The plasma complement system comprises several activation pathways that sha re a common terminal route involving the assembly of the terminal complemen t complex (TCC), formed by C5b-C9. The order of emergence of the homologous components of TCC (C6, C7, C8 alpha, C8 beta, and C9) has been determined by phylogenetic analyses of their amino acid sequences. Using all the seque nce data available for C6-C9 proteins, as well as for perforins, the result s suggested that these TCC components originated from a single ancestral ge ne and that C6 and. C7 were the earliest to emerge. Our evidence supports t he notion that the ancestral gene had a complex modular composition. A seri es of gene duplications in combination with a tendency to lose modules resu lted in successive complement proteins with decreasing modular complexity. C9 and perforin apparently are the result of different selective conditions to acquire pore-forming function. Thus C9 and perforin are examples of evo lutionary parallelism.