Summary
Various rodent and primate DNAs exhibit a stronger intra- than interspecies cross-hybridization with probes derived from the N-terminal domain exons of human and rat carcinoembryonic antigen (CEA)-like genes. Southern analyses also reveal that the human and rat CEA gene families are of similar complexity. We counted at least 10 different genes per human haploid genome. In the rat, approximately seven to nine different N-terminal domain exons that presumably represent different genes appear to be present. We were able to assign the corresponding genomic restriction endonuclease fragments to already isolated CEA gene family members of both human and rat. Highly similar subgroups, as found within the human CEA gene family, seem to be absent from the rat genome. Hybridization with an intron probe from the human nonspecific cross-reacting antigen (NCA) gene and analysis of DNA sequence data indicate the conservation of noncoding regions among CEA-like genes within primates, implicating that whole gene units may have been duplicated. With the help of a computer program and by calculating the rate of synonymous substitutions, evolutionary trees have been derived. From this, we propose that an independent parallel evolution, leading to different CEA gene families, must have taken place in, at least, the primate and rodent orders.
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Barker WC, Ketcham LK, Dayhoff MO (1980) Origins of immunoglobulin heavy chain domains. J Mol Evol 15:113–127
Beauchemin N, Benchimol S, Cournoyer D, Fuks A, Stanners CP (1987) Isolation and characterization of full-length functional cDNA clones for human carcinoembryonic antigen. Mol Cell Biol 7:3221–3230
Bialojan S, Falkenburg D, Renkawitz-Pohl R (1984) Characterization and developmental expression of βtubulin genes inDrosophila melanogaster. EMBO J 3:2543–2548
Britten RY (1986) Rates of DNA sequence evolution differ between taxonomic groups. Science 231:1393–1398
Busslinger M, Rusconi S, Birnstiel ML (1982) An unusual evolutionary behaviour of a sea urchin histone gene cluster. EMBO J 1:27–33
Chang L-YE, Slightom JL (1984) Isolation and nucleotide sequence analysis of the β-type globin pseudogene from human, gorilla and chimpanzee. J Mol Biol 180:767–784
Cohen JB, Effron K, Rechavi E, Ben-Neriah Y, Zakut R, Givol D (1982) Simple DNA sequences in homologous flanking regions near immunoglobulin VH genes: a role in gene interaction? Nucleic Acids Res 10:3353–3370
Engvall E, Shively JE, Wrann M (1978) Isolation and characterization of the normal crossreacting antigen: homology of its NH2-terminal domain with that of carcinoembryonic antigen. Proc Natl Acad Sci USA 75:1670–1674
Felsenstein J (1985) Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39:783–791
Gilbert W (1978) Why genes in pieces? Nature 271:501
Gold P, Freedman SO (1965a) Demonstration of tumor-specific antigens in human colonic carcinomata by immunological tolerance and absorption techniques. J Exp Med 121:439–462
Gold P, Freedman SO (1965b) Specific carcinoembryonic antigens of the human digestive system. J Exp Med 122:467–480
Goodman M, Koop BF, Czelusniak J, Weiss ML, Slightom JL (1984) The ν-globin gene: its long evolutionary history in the β-globin family of mammals. J Mol Biol 180:803–823
Haagensen DE Jr, Metzgar RS, Swenson B, Dilley WG, Cox CE, Davis S, Murdoch J, Zamcheck N, Wells SA Jr (1982) Carcinoembryonic antigen in nonhuman primates. J Natl Cancer Inst 69:1073–1076
Harlow P, Litwin S, Nemer M (1988) Synonymous nucleotide substitution rates of β-tubulin and histone genes conform to high overall genomic rates in rodents but not in sea urchins. J Mol Evol 27:56–64
Hinoda J, Neumaier M, Hefta SA, Drzeniek Z, Wagener C, Shively L, Hefta LJF, Shively JE, Paxton RJ (1988) Molecular cloning of a cDNA coding biliary glycoprotein I: primary structure of a glycoprotein immunologically crossreactive with carcinoembryonic antigen. Proc Natl Acad Sci USA 85:6959–6963
jantscheff P, Indzhiia V, Micheel B (1986) Search for CEA-like molecules in polymorphonuclear leukocytes of nonhuman primates using monoclonal antibodies. Arch Geschwulstforsch 56:113–116
Keller EB, Noon WA (1984) Intron splicing: a conserved internal signal in introns of animal pre-mRNAs. Proc Natl Acad Sci USA 81:7417–7420
Kessler MJ, Shively JE, Pritchard DG, Todd CW (1978) Isolation, immunological characterization, and structural studies of a tumor antigen related to carcinoembryonic antigen. Cancer Res 38:1041–1048
Kodelja V, Lucas K, Barnert S, von Kleist S, Thompson JA, Zimmermann W (1989) Identification of a carcinoembryonic antigen (CEA) gene family in the rat: analysis of the N-terminal domains reveals immunoglobulin-like, hypervariable regions. J Biol Chem (in press)
Koop BF, Goodman M, Xu P, Chan K, Slightom JL (1986) Primate ν-globin sequences and man's place among the great apes. Nature 319:234–238
Li W-H (1981) Simple method for constructing phylogenetic trees from distance matrices. Proc Natl Acad Sci USA 78: 1085–1089
Li W-H, Wu Ch-I, Luo C-C (1985) A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Mol Biol Evol 2:150–174
Li W-H, Tanimura M, Sharp PM (1987) An evaluation of the molecular clock hypothesis using mammalian DNA sequences. J Mol Evol 26:330–342
Miyata T, Yasunaga T, Nishida T (1980) Nucleotide sequence divergence and functional constraint in mRNA evolution. Proc Natl Acad Sci USA 77:7328–7332
Needleman SB, Wunsch CD (1970) A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol 48:443–453
Neumaier M, Zimmermann W, Shively L, Hinoda Y, Riggs AD (1988) Characterization of a cDNA clone for the nonspecific crossreacting antigen (NCA) and a comparison of NCA and carcinoembryonic antigen (CEA). J Biol Chem 263:3202–3207
Oikawa S, Imajo S, Nogouchi T, Kosaki G, Nakazato H (1987a) The carcinoembryonic antigen (CEA) contains multiple immunoglobulin-like domains. Biochem Biophys Res Commun 144:634–642
Oikawa S, Kosaki G, Nakazato H (1987b) Molecular cloning of a gene for a member of carcinoembryonic antigen (CEA) gene family; signal peptide and N-terminal domain sequences of nonspecific crossreacting antigen (NCA). Biochem Biophys Res Commun 146:464–469
Oikawa S, Nakazato H, Kosaki G (1987c) Primary structure of human carcinoembryonic antigen (CEA) deduced from cDNA sequence. Biochem Biophys Res Commun 142:511–518
Paxton RJ, Mooser G, Pande H, Lee TD, Shively JE (1987) Sequence analysis of carcinoembryonic antigen: identification of glycosylation sites and homology with the immunoglobulin supergene family. Proc Natl Acad Sci USA 84:920–924
Perler F, Efstratiadis A, Lomedico P, Gilbert W, Kolodner R, Dodgson J (1980) The evolution of genes: the chicken preproinsulin gene. Cell 20:555–566
Sakoyama Y, Hong K-J, Byun SM, Hisajima H, Ueda S, Yaoita Y, Hayashida H, Miyata T, Honjo T (1987) Nucleotide sequences of immunoglobulin ∈ genes of chimpanzee and orangutan: DNA molecular clock and hominoid evolution. Proc Natl Acad Sci USA 84:1080–1084
Shilo B-Z (1987) Proto-oncogenes inDrosophila melanogaster. Trends Genet 3:69–72
Slightom JL, Blechl AE, Smithies O (1980) Human Gγ- and Aγ-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell 21:627–638
Tawaragi Y, Oikawa S, Matsuoka Y (1988) Primary structure of nonspecific crossreacting antigen (NCA), a member of carcinoembryonic antigen (CEA) gene family, deduced from cDNA sequence. Biochem Biophys Res Commun 150:89–96
Thompson J, Zimmermann W (1988) The carcinoembryonic antigen (CEA) gene family: structure, expression and evolution. Tumor Biol 9:63–83
Thompson JA, Pande H, Paxton RJ, Shively L, Padma A, Simmer RL, Todd CW, Riggs AD, Shively JE (1987) Molecular cloning of a gene belonging to the carcinoembryonic antigen gene family and discussion of a domain model. Proc Natl Acad Sci USA 84:2965–2969
Thompson JA, Mauch E-M, Chen F-S, Hinoda Y, Schrewe H, Ortlieb B, Barnert S, von Kleist S, Shively JE, Zimmermann W (1989) Analyses of the size of the carcinoembryonic antigen (CEA) gene family: isolation and sequencing of N-terminal domain exons. Biochem Biophys Res Commun 158: 996–1004
Wahren B, Gadler F, Gahrten G, Hammerström S, Hareland Y, Hyden N, Ljungdahl E, Mahlen A, Ruden U, Wiklund M (1983) NCA: a differentiation antigen of myelopoietic cells in humans and hominoid monkeys. Ann NY Acad Sci USA 417:344–358
Watanabe S, Chou JY (1988a) Isolation and characterization of complementary DNAs encoding human pregnancy-specific β1-glyprotein. J Biol Chem 263:2049–2054
Watanabe S, Chou JY (1988b) Human pregnancy-specific β1-glycoprotein: a new member of the carcinoembryonic antigen gene family. Biochem Biophys Res Commun 152:762–768
Williams AF (1987) A year in the life of the immunoglobulin superfamily. Immunol Today 8:298–303
Wu C-I, Li W-H (1985) Evidence for higher rates of nucleotide substitution in rodents than in man. Proc Natl Acad Sci USA 82:1741–1745
Zimmermann W, Ortlieb B, Friedrich R, von Kleist S (1987) Isolation of cDNA clones encoding the human carcinoembryonic antigen reveal a highly conserved repeating structure. Proc Natl Acad Sci USA 84:2960–2964
Zimmermann W, Weber B, Ortlieb B, Rudert F, Schempp W, Fiebig H-H, Shively JE, von Kleist S, Thompson JA (1988) Chromosomal localization of the carcinoembryonic antigen gene family and differential expression in various tumors. Cancer Res 48:2250–2254
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Rudert, F., Zimmermann, W. & Thompson, J.A. Intra- and interspecies analyses of the carcinoembryonic antigen (CEA) gene family reveal independent evolution in primates and rodents. J Mol Evol 29, 126–134 (1989). https://doi.org/10.1007/BF02100111
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DOI: https://doi.org/10.1007/BF02100111