Ancient origin of human complement factor H.
We studied the evolutionary history of two homologous proteins of the human complement system, factor H (FH) and the alpha chain of the C4b binding protein (C4bpalpha), and included in this study the related proteins from the barred sand bass (P. nebulifer) and the nematode C. elegans. Phylogenetic trees inferred from individual short consensus repeats (SCRs) and divergence among repeats from different genes suggest that human FH has a much closer evolutionary relationship to putative complement components from P. nebulifer and C. elegans than does the C4bpalpha. This indicates that a member of the alternative pathway of the complement system (FH) has an ancient origin, while a homologous member of the classical pathway (C4bpalpha) appeared later in evolutionary history as a result of gene duplication. The ancient evolutionary position of FH is in agreement with the suggestion that the alternative pathway of the complement system is older than the classical pathway. Phylogenetic analysis also shows that the sand bass cofactor protein SBP1 and cofactor related protein SBCRP-1 have diverged very recently.
Krushkal
J
J
Research Center for Human Genetics, Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center, 2121 Holcombe Boulevard, Houston, TX 77030, USA.
Kemper
C
C
Gigli
I
I
D000595:Amino Acid Sequence; D000818:Animals; D015935:Complement C4b / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics*; D003169:Complement Inactivator Proteins; D019143:Evolution, Molecular; D006023:Glycoproteins; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
C493495:CFH protein, human; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D011951:Receptors, Complement; D015935:Complement C4b; D017242:Complement Factor H