Abstract
The human complement component 4 is encoded in two genes, C4A and C4B, residing between the class I and class II genes of the major histocompatibility complex. The C4A and C4B molecules differ in their biological activity, the former binding more efficiently to proteins than to carbohydrates while for the latter, the opposite holds true. To shed light on the origin of the C4 genes we isolated cosmid clones bearing the C4 genes of a chimpanzee, a gorilla, and an orang-utan. From the clones, we isolated the fragments coding for the C4d part of the gene (exons and introns) and sequenced them. Altogether we sequenced eight gene fragments: three chimpanzee (Patr-C4-1 *01, Patr-C4-1 *02, Patr-C4-2 *01), two gorilla (Gogo-C4-1 *01, Gogo-C4-2 *01), and three orang-utan (Popy-C4-1 *01, Popy-C4-2 *01, Popy-C4-3 *01). Comparison of the sequences with each other and with human C4 sequences revealed that in the region believed to be responsible for the functional difference between the C4A and C4B proteins the C4A genes of the different species fell into one group and the C4B genes fell into another. In the rest of the sequence, however, the C4A and C4B genes of each species resembled each other more than they did C4 genes of other species. These results are interpreted as suggesting extensive homogenization (concerted evolution) of the C4 genes in each species, most likely by repeated unequal, homologous, intragenic crossing-over.
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References
Belt, K. T., Carroll, M. C., and Porter, R. R.: The structural basis of the multiple forms of human complement component C4. Cell 36: 907–914, 1984
Belt, K. T., Yu, C. Y., Carroll, M. C.,and Porter, R. R.: Polymorphism of human complement component C4. Immunogenetics 21: 173–180, 1985
Bitter-Suermann, D., Krönke, M., Brade, V., and Hadding, U.: Inherited polymorphism of guinea pig factor B and C4: evidence for genetic linkage between the C4 and B floci. J Immunol 118: 1822–1826, 1977
Carroll, M. C., Belt, T., Palsdottir, A., and Porter, R. R.: Structure and organization of the C4 genes. Philos Trans R Soc Lond [Biol] 306: 379–388, 1984
Conner, B. J., Reyes, A. A., Morin, C., Itakura, K., Teplitz, R. L., and Wallace, R. B.: Detection of sickle cell βs-globin allele by hybridization with synthetic oligonucleotides. Proc Natl Acad Sci USA 80: 278–282, 1983
Davis, L. G., Dibner, M. D., and Battey, J. F.: Basic Methods in Molecular Biology. Elsevier, New York, 1986
De Kroon, A. I. P. M., Doxiadis, G., Doxiadis, I., and Hensen, E. J. Structure and polymorphism of the feline complement component C4. Immunogenetics 24: 202–205, 1986
Dodds, A. W. and Law, A. S. K.: The complement component C4 of mammals. Biochem J 265: 495–502, 1990
Dover, G., Brown, S., Coen, E., Dallas, J., Strachan, T., and Trick, M.: Dynamics of genome evolution and species differentiation. In G. A. Dover and R. B. Flavell (eds.): Genome Evolution, pp. 343–372, Academic Press, London, 1982
Doxiadis, G., Rebmann, V., Doxiadis, I., Krumbacher, K., Vriesendorp, H. M., and Grosse-Wilde, H.: Polymorphism of the fourth complement component in the dog. Immunobiology 169: 563–569, 1985
Felsenstein, J.: Phylogenies from molecular sequences: Inference and reliability. Annu Rev Genet 22: 521–565, 1988
Granados, J., Awdeh, Z. L., Chen, J.-H., Giles, C. M., Balner, H., Yunis, E. J., and Alper, C. A.: There are two C4 genetic loci and a null allele in the chimpanzee. Immunogenetics 26: 344–350, 1987
Hauptmann, G., Goetz, J., Uring-Lambert, B., and Grosshans, E.: Component deficiencies. 2. The fourth component. Prog Allergy 39: 232–249, 1986
Insenman, D. E. and Young, J. R.: The molecular basis for the difference in immune hemolysis activity of the Chido and Rodgers isotypes of human complement component C4. J Immunol 132: 3019–3027, 1984
Kawaguchi, H. and Klein, J.: Organization of C4 and CYP21 loci in gorilla and orang-utan. Hum Immunol, submitted 1991
Kawaguchi, H., Golubic, M., Figueroa, F., and Klein, J.: Organization of the chimpanzee C4-CYP21 region: Implications for the evolution of human genes. Eur J Immunol 20: 739–745, 1990
Kawaguchi, H., O'hUigin, C., and Klein, J.: Evolution of primate C4 and CYP21 genes. In J. Klein and D. Klein (eds.): Molecular Evolution of the Major Histocompatibility Complex, pp. 357–382, Springer, Heidelberg, 1991
Kay, P. H. and Dawkins, R. L.: Genetic polymorphism of complement C4 in the dog. Tissue Antigens 23: 151–155, 1984
Kimura, M.: A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 16: 111–120, 1980
Klein, J., Bontrop, R. E., Dawkins, R. L., Erlich, H. A., Gyllensten, U. B., Heise, E. R., Jones, P. P., Wakeland, E. K., and Watkins, D. I.: Nomenclature for the major histocompatibility complexes of different species: A proposal. Immunogenetics 31: 217–219, 1990
Law, S. K. A., Dodds, A. W., and Porter, R. R.: A comparison of the properties of two classes, C4A and C4B, of the human complement component C4. EMBO J 3: 1819–1823, 1984
Lévi-Strauss, M., Tosi, M., Steinmetz, M., Klein, J., and Meo, T.: Multiple duplications of complement C4 gene correlate with H-2-controlled testosterone-independent expression of its sex-limited isoform, C4-Slp. Proc Natl Acad Sci USA 82: 1746–1750, 1985
Maniatis, T., Fritsch, E. F., and Sambrook, J.: Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Press, Cold Spring Harbor, 1982
Mauff, G., Alper, C. A., Awdeh, Z., Batchelor, J. R., Bertrams, T., Braun-Petersen, G., Dawkins, R. L., Demant, P., Edwards, J., Grosse-Wilde, H., Hauptmann, G., Klouda, P., Lamm, L., Mullenhauer, E., Nerl, C., Olaisen, B., O'Neill, G. O., Rittner, C., Roos, M. H., Skanes, V., Teisberg, P., and Wells, L.: Statement on the nomenclature of human C4 allotypes. Immunobiology 164: 184–191, 1983
Mayer, W. E., Jonker, M., Klein, D., Ivanyi, P., van Seventer, G., and Klein, J.: Nucleotide sequences of chimpanzee MHC class I alleles: Evidence for trans-species mode of evolution. EMBO J 7: 2765–2774, 1988
O'Neill, G. J., Yang, S. Y., and Dupont, B.: Two HLA-linked loci controlling the fourth component of human complement. Proc Natl Acad Sci USA 75: 5165–5169, 1978
Rasheed, S. A., Rongey, R. W., Bruszweski, J., Nelson-Rees, W. A., Rabin, H., Neubauer, R. H., Esra, G., and Gardner, M. B.: Establishment of a cell line with associated Epstein-Barr-like virus from a leukemic orang-utan. Science 198: 407–409, 1977
Reid, K. B. M.: Application of molecular cloning to studies of the complement system. Immunology 55: 185–196, 1985
Ripley, L. S. and Glickman, B. W.: Unique self-complementarity of palindromic sequences provides DNA structural intermediates for mutation. Cold Spring Harbor Symp Quant Biol 47: 851–861, 1982
Roos, M. H., Atkinson, J. P., and Shreffler, D. C.: Molecular characterization of the Ss and Slp (C4) proteins of the mouse H-2 complex: Subunit composition, chain-size polymorphism, and an intracellular (Pro-Ss) precursor. J Immunol 121: 1106–1115, 1978
Ross, G. D. (ed.): Immunobiology of the Complement System. An Introduction for Research and Clinical Medicine. Academic Press, Orlando, 1986
Saitou, N. and Nei, M.: The neighbor-joining method. A new method for reconstructing phylogenetic trees. Mol Biol Evol 4: 406–425, 1987
Sanger, F., Nicklen, S., and Coulson, A. R.: DNA sequencing with chain terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977
Schneider, P. M., Carroll, M. S., Alper, C. A., Rittner, C., Whitehead, A. S., Yunis, E. J., and Colten, H. R.: Polymorphism of the human complement C4 and steroid 21-hydroxylase genes. J Clin Inv 78: 650–657, 1986
Spilliaert, R., Palsdottir, A., and Arnason, A.: Analysis of the C4 genes in baleen whales using a human cDNA probe. Immunogenetics 32: 73–76, 1990
Steinmetz, M., Stephan, D., Dastronikoo, G. R., Gibb, E., and Romaniuk, R. In J. Lefkovits and B. Pernis (eds.): Immunological Methods. Academic Press, New York, 1985
Tosi, M., Lévi-Strauss, M., Duponchel, C., and Meo, T.: Sequence heterogeneity of murine complementary DNA clones related to the C4 and C4-Slp isoforms of the fourth complement component. Philos Trans R Soc Lond [Biol] 306: 389–394, 1984
Yu, C. Y.: The complete exon-intron structure of a human complement component C4A gene. DNA sequences, polymorphism, and linkage to the 21-hydroxylase gene. J Immunol 146: 1057–1066, 1991
Yu, C. Y., Belt, K. T., Giles, C. M., Campbell, R. D., and Porter, R. R.: Structural basis of the polymorphism of human complement components C4A and C4B: gene size, reactivity and antigenicity. EMBO J 5: 2873–2881, 1986
Yu, C. Y., Campbell, R. D., and Porter, R. R.: A structural model for the location of the Rodgers and the Chido antigenic determinants and their correlation with the human complement C4A/C4B isotypes. Immunogenetics 27: 399–405, 1988
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Kawaguchi, H., Zaleska-Rutczynska, Z., Figueroa, F. et al. C4 genes of the chimpanzee, gorilla, and orang-utan: evidence for extensive homogenization. Immunogenetics 35, 16–23 (1992). https://doi.org/10.1007/BF00216622
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DOI: https://doi.org/10.1007/BF00216622