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 ct chain of the C4b bin ding protein (C4bp alpha), and included in this study the related prot eins from the barred sand bass (P. nebulifer) and the nematode C. eleg ans, Phylogenetic trees inferred from individual short consensus repea ts (SCRs) and divergence among repeats from different genes suggest th at human FH has a much closer evolutionary relationship to putative co mplement components from P. nebulifer and C. elegans than does the C4b p alpha. This indicates that a member of the alternative pathway of th e complement system (FH) has an ancient origin, while a homologous mem ber of the classical pathway (C4bpa) appeared later in evolutionary hi story as a result of gene duplication. The ancient evolutionary positi on of FH is in agreement with the suggestion that the alternative path way of the complement system is older than the classical pathway. Phyl ogenetic analysis also shows that the sand bass cofactor protein SBP1 and cofactor related protein SBCRP-1 have diverged very recently.