Complement System: Evolution

Masaru Nonaka, University of Tokyo, Japan
Reo Sekiguchi, University of Tokyo, Japan

Published online: January 2013

DOI: 10.1002/9780470015902.a0006135.pub3

The human complement system is one of the principal effector systems of innate immunity and consists of more than 30 serum and cell surface proteins. Most complement components show a striking modular structure, which makes evolutionary studies feasible. The evolutionary origin of the complement system can be traced back to the common ancestor of eumetazoa, predating by far the origin of the canonical adaptive immunity unique to the jawed vertebrates. Although the complement system has been conserved by all deuterostomes analysed thus far, it has been lost multiple times independently in the protostome lineage. Sophistication of the complement system from a simpler system by gene duplications and exon shuffling occurred in the vertebrate lineage.

Key Concepts:

  • The complement system is one of the most ancient body defence mechanisms of eumetazoa.
  • Most complement components have a characteristic modular structure.
  • The modern complement system was established in a common ancestor of jawed vertebrates by gene duplication and exon shuffling of the primitive complement genes.
  • The complement system has been lost multiple times independently in protostome lineages, whereas it has been retained by all deuterostomes analysed so far.
  • The thioester-containing protein family is subdivided into two subfamilies, the C3 and A2M subfamilies.

Keywords: gene duplication; modular structure; innate immunity; deuterostome; protostome; cnidaria

Figure 1. Modular structure of human complement components and chromosomal localisation of the encoding genes. Protein module designation and modular structure are adapted from Volanakis and Frank (1998). Chromosomal localisation of the complement genes is adapted from the Complement Genetics Website (http://www.complement-genetics.uni-mainz.de/chromtab.htm).
Figure 2. Phylogenetic tree of TEP family. The entire amino acid sequences were aligned by ClustalX and MEGA5, and phylogenetic tree was constructed using the neighbour-joining method based on the poisson model. The analysis involved 41 amino acid sequences. In this tree, gaps in the alignment were excluded. There were a total of 954 positions in the final dataset. The scale bar indicates substitutions/site.
Figure 3. Hypothetical evolutionary history of the genes for MASP, C1r and C1s (Nonaka and Miyazawa, 2002).
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 Web Links
    ePath B-factor, properdin (BF); Locus ID: 629. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=629
    ePath B-factor, properdin (BF); MIM number: 138470. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?138470
    ePath Complement component 4A (C4A); Locus ID: 720. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=720
    ePath Complement component 4A (C4A); MIM number: 120810. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?120810
    ePath Complement Genetics Website. Chromosomal localization of complement genes and linkage groups http://www.complement-genetics.uni-mainz.de/chromtab.htm
    ePath Mannan-binding lectin serine protease 1 (C4/C2 activating component of Ra-reactive factor) (MASP1); MIM number: 600521. OMIM:http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600521
    ePath Mannan-binding lectin serine protease 1 (C4/C2 activating component of Ra-reactive factor) (MASP1); Locus ID: 5648. LocusLink:http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5648
    ePath Proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional protease 7) (PSMB8); Locus ID: 5696. LocusLink:http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5696
    ePath Proteasome (prosome, macropain) subunit, beta type, 8 (large multifunctional protease 7) (PSMB8); MIM number: 177046. OMIM:http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?177046
    ePath Transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) (TAP1); Locus ID: 6890. LocusLink:http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6890
    ePath Transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) (TAP1); MIM number: 170260. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?170260

Related Sub-Topics:

Complement | Molecular Evolution | Protein Evolution
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Article Title: Complement System: Evolution
 
How to Cite close
Nonaka, Masaru, and Sekiguchi, Reo(Jan 2013) Complement System: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006135.pub3]