title: Phylogenetic analysis of the homologous proteins of the terminal complement complex supports the emergence of C6 and C7 followed by C8 and C9.
abstract: The plasma complement system comprises several activation pathways that share a common terminal route involving the assembly of the terminal complement complex (TCC), formed by C5b-C9. The order of emergence of the homologous components of TCC (C6, C7, C8alpha, C8beta, and C9) has been determined by phylogenetic analyses of their amino acid sequences. Using all the sequence data available for C6-C9 proteins, as well as for perforins, the results suggested that these TCC components originated from a single ancestral gene and that C6 and C7 were the earliest to emerge. Our evidence supports the notion that the ancestral gene had a complex modular composition. A series of gene duplications in combination with a tendency to lose modules resulted 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 evolutionary parallelism.
authors.affiliation: Department of Immunology, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, A.P. 70228, 04510 México, D.F., México.
authors.forename: M
authors.initials: M
authors.lastname: Mondragón-Palomino
authors.forename: D
authors.initials: D
authors.lastname: Piñero
authors.forename: A
authors.initials: A
authors.lastname: Nicholson-Weller
authors.forename: J P
authors.initials: JP
authors.lastname: Laclette
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003182:Complement C5 / Q000235:genetics; D050776:Complement C5b; D003183:Complement C6 / Q000737:chemistry / Q000235:genetics*; D003184:Complement C7 / Q000737:chemistry / Q000235:genetics*; D003185:Complement C8 / Q000737:chemistry / Q000235:genetics*; D003186:Complement C9 / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D054353:Perforin; D010802:Phylogeny; D052899:Pore Forming Cytotoxic Proteins; D011817:Rabbits; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013995:Time
chemical_list: D003182:Complement C5; D003183:Complement C6; D003184:Complement C7; D003185:Complement C8; D003186:Complement C9; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D050776:Complement C5b