Document Detail

Genetics of human complement component C4 and evolution the central MHC.
MedLine Citation:
PMID:  11487475     Owner:  NLM     Status:  MEDLINE    
The two classes of human complement component C4 proteins C4A and C4B manifest differential chemical reactivities and binding affinities towards target surfaces and complement receptor CR1. There are multiple, polymorphic allotypes of C4A and C4B proteins. A complex multiplication pattern of C4A and C4B genes with variations in gene size, gene dosage and flanking genes exists in the population. This is probably driven by the selection pressure to respond to a great variety of parasites efficiently and effectively, which the bony fish achieved through the multiplication and diversification of the related complement C3 proteins. Complement C4, C3 and C5 belong to the alpha2 macroglobulin protein family but acquired specific features that include an anaphylatoxin domain, a netrin (NTR) domain, and stretches of basic residues for proteolytic processings to form multiple chain structures. Complement C3 and C4 are important in the innate immune response as they opsonize parasites for phagocytosis. The emergence of complement C3 predates proteins involved in the adaptive immune response as C3 is present in deuterostome invertebrates such as echinoderms. The human C4 genes are located in the central MHC at chromosome 6p21.3. C3 and C5 are located at chromosome 19 and 9, respectively, with representatives of the other groups of genes paralogous to the MHC at 19p13.1-p13.3, 1q21-25, and 9q33-34. The central MHC also contains genes for complement components C2 and Bf. These genes appear to have similar evolutionary histories to C3/C4/C5 and are used here to illustrate stepwise processes resulting in co-location of diverse domains, chromosomal duplication, local segmental duplication and divergence of sequence and function. This model of evolution is useful in the investigation of innate and acquired immunity and in seeking explanations for diseases associated with MHC ancestral haplotypes.
O P Martinez; N Longman-Jacobsen; R Davies; E K Chung; Y Yang; S Gaudieri; R L Dawkins; C Y Yu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review     Date:  2001-08-01
Journal Detail:
Title:  Frontiers in bioscience : a journal and virtual library     Volume:  6     ISSN:  1093-4715     ISO Abbreviation:  Front. Biosci.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-08-06     Completed Date:  2001-12-13     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9709506     Medline TA:  Front Biosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  D904-13     Citation Subset:  IM    
Centre for Molecular Immunology and Instrumentation, University of Western Australia, PO Box 5100, Canning Vale WA 6155, Australia.
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MeSH Terms
Amino Acid Sequence
Autoimmune Diseases / genetics
Complement C4 / genetics*
Complement System Proteins / genetics
Evolution, Molecular*
Genetic Variation
Major Histocompatibility Complex*
Molecular Sequence Data
Sequence Homology, Amino Acid
Terminology as Topic
Grant Support
Reg. No./Substance:
0/Complement C4; 9007-36-7/Complement System Proteins

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