Chemical evidence for common genetic ancestry of complement components C3 and C5

Sequence studies reveal a marked similarity between the partial primary structures of human C3a and C5a anaphylatoxins. Eight of the first 25 residues are identical when threonine at position 1 in C5a is aligned with glutamine at position 3 in C3a and one gap is inserted in the C3a sequence. A unique cysteinyl-cysteine sequence is conserved in the 2 molecules, which further suggests a genetic relatedness. Computer-generated alignment scores from comparison of the NH2-terminal portions of human C3a and C5a exceeded by 4 standard deviations the score from random permutations of these same sequences. This sequence similarity between the two anaphylatoxins suggests that the respective precursors, C3 and C5, had a common genetic ancestry. The proposed genetic relationship between C3 and C5 may express itself functionally through a similar molecular behavior in complement-dependent cytolysis.