Complement System: Evolution

Abstract

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 thioesterÔÇÉcontaining 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 . 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, ).

close

References

Ariki S, Takahara S, Shibata T et al. (2008) Factor C acts as a lipopolysaccharide‐responsive C3 convertase in horseshoe crab complementactivation. Journal of Immunology 181: 7994–8001.

Blandin S and Levashina EA (2004) Thioester‐containing proteins and insect immunity. Molecular Immunology 40: 903–908.

Carroll MC, Campbell RD, Bentley DR and Porter RR (1984) A molecular map of the human major histocompatibility complex class III region linking complement genes C4, C2 and factor B. Nature 307: 237–241.

Dahl MR, Thiel S, Matsushita M et al. (2001) MASP‐3 and its association with distinct complexes of the mannan‐binding lectin complement activation pathway. Immunity 15: 127–135.

Dodds AW and Law SK (1998) The phylogeny and evolution of the thioester bond‐containing proteins C3, C4 and alpha 2‐macroglobulin. Immunological Reviews 166: 15–26.

Fujito NT, Sugimoto S and Nonaka M (2010) Evolution of thioester‐containing proteins revealed by cloning and characterization of their genes from a cnidarian sea anemone, Haliplanella lineate. Developmental and Comparative Immunology 34: 775–784.

Janssen BJ, Huizinga EG, Raaijmakers HC et al. (2005) Structures of complement component C3 provide insights into the function and evolution of immunity. Nature 437: 505–511.

Jing H, Xu YY, Carson M et al. (2000) New structural motifs on the chymotrypsin fold and their potential roles in complement factor B. EMBO Journal 19: 164–173.

Kasahara M (1999) The chromosomal duplication model of the major histocompatibility complex. Immunological Review 167: 17–32.

Kimura A, Sakaguchi E and Nonaka M (2009) Multi‐component complement system of Cnidaria: C3, Bf, and MASP genes expressed in the endodermal tissues of a sea anemone, Nematostella vectensis. Immunobiology 214: 165–178.

King N, Westbrook MJ, Young SL et al. (2008) The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451: 783–788.

Levashina EA, Moita LF, Blandin S et al. (2001) Conserved role of a complement‐like protein in phagocytosis revealed by dsRNA knockout in cultured cells of the mosquito, Anopheles gambiae. Cell 104: 709–718.

Li ZF, Wu XH and Engvall E (2004) Identification and characterization of CPAMD8, a novel member of the complement 3/alpha2‐macroglobulin family with a C‐terminal Kazal domain. Genomics 83: 1083–1093.

Lin M, Sutherland DR, Horsfall W et al. (2002) Cell surface antigen CD109 is a novel member of the alpha(2) macroglobulin/C3, C4, C5 family of thioester‐containing proteins. Blood 99: 1683–1691.

Nakao M, Mutsuro J, Nakahara M, Kato Y and Yano T (2003) Expansion of genes encoding complement components in bony fish: biological implications of the complement diversity. Developmental and Comparative Immunology 27: 749–762.

Nonaka M (2001) Evolution of the complement system. Current Opinion in Immunology 13: 69–73.

Nonaka M (2011) The complement C3 protein family in invertebrates. Invertebrate Survival Journal 8: 21–32.

Nonaka M and Kimura A (2006) Genomic view of the evolution of the complement system. Immunogenetics 58: 701–713.

Nonaka M and Miyazawa S (2002) Evolution of the initiating enzymes of the complement system. Genome Biology 3: 1001.1–1001.5.

Putnam NH, Srivastava M, Hellsten U et al. (2007) Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization. Science 317: 86–94.

Sekiguchi R, Fujito NT and Nonaka M (2012) Evolution of the thioester‐containing proteins (TEPs) of the arthropoda, revealed by molecular cloning of TEP genes from a spider, Hasarius adansoni. Developmental and Comparative Immunology 36: 483–489.

Sottrup‐Jensen L, Stepanik TM, Kristensen T et al. (1985) Common evolutionary origin of alpha 2‐macroglobulin and complement components C3 and C4. Proceedings of the National Academy of Sciences of the USA 82: 9–13.

Srivastava M, Simakov O, Chapman J et al. (2010) The Amphimedon queenslandica genome and the evolution of animal complexity. Nature 466: 720–726.

Tosi M, Duponchel C, Meo T and Couture‐Tosi E (1989) Complement genes C1r and C1s feature an intronless serine protease domain closely related to haptoglobin. Journal of Molecular Biology 208: 709–714.

Venter JC, Adams MD, Myers EW et al. (2001) The sequence of the human genome. Science 291: 1304–1351.

Volanakis JE and Frank MM (eds) (1998) The Human Complement System in Health and Disease., p. 1–656. New York: Marcel Dekker.

Zarkadis IK, Mastellos D and Lambris JD (2001) Phylogenetic aspects of the complement system. Developmental and Comparative Immunology 25: 745–762.

Further Reading

Flajnik MF and Kasahara M (2001) Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 15: 351–362.

Fujita T (2002) Evolution of the lectin‐complement pathway and its role in innate immunity. Nature Reviews Immunology 2: 346–353.

Hoffmann JA, Kafatos FC, Janeway CA and Ezekowitz RA (1999) Phylogenetic perspectives in innate immunity. Science 284: 1313–1318.

Miyazawa S, Azumi K and Nonaka M (2001) Cloning and characterization of integrin alpha subunits from the solitary ascidian, Halocynthia roretzi. Journal of Immunology 166: 1710–1715.

Ohno S (1970) Evolution by Gene Duplication. New York: Springer.

Smith LC, Clow LA and Terwilliger DP (2001) The ancestral complement system in sea urchins. Immunological Review 180: 16–34.

Suzuki MM, Satoh N and Nonaka M (2002) C6‐like and C3‐like molecules from the cephalochordate, amphioxus, suggest a cytolytic complement system in invertebrates. Journal of Molecular Evolution 54: 671–679.

Terado T, Smith SL, Nakanishi T et al. (2001) Occurrence of structural specialization of the serine protease domain of complement factor B at the emergence of jawed vertebrates and adaptive immunity. Immunogenetics 53: 250–254.

Zhu Y, Thangamani S, Ho B and Ding JL (2005) The ancient origin of the complement system. EMBO Journal 24: 382–394.

Web Links

B‐factor, properdin (BF); Locus ID: 629. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=629

B‐factor, properdin (BF); MIM number: 138470. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?138470

Complement component 4A (C4A); Locus ID: 720. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=720

Complement component 4A (C4A); MIM number: 120810. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?120810

Complement Genetics Website. Chromosomal localization of complement genes and linkage groups http://www.complement‐genetics.uni‐mainz.de/chromtab.htm

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

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

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

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

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

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

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

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]