Abstract
We present the nucleotide sequences of four members of the six-member human salivary prolinerich protein (PRP) gene family. The four genes are PRB1 and PRB2, which encode basic PRPs, and PRB3 and PRB4, which encode glycosylated PRPs. Each PRB gene is approximately 4.0 kb in length and contains four exons, the third of which is entirely composed of 63-bp tandem repeats and encodes the proline-rich portion of the protein products. Exon 3 contains different numbers of tandem repeats in the different PRB genes. Variation in the numbers of these repeats is also responsible for length variations in different alleles of the PRB genes. We have determined a probable evolutionary history of the human PRP gene family by comparing the nucleotide sequences of the six PRP genes. The present-day six PRP loci probably evolved from a single ancestral gene by four sequential gene duplications, leading to six genes that fall into three subsets, each consisting of two genes. During this evolutionary process, multiple rearrangements and gene conversion occurred mainly in the region from the 3′ end of IVS2 and the 3′ end of exon 3.
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Azen, E.A., Lyons, K.M., Mcgonigal, T., Barrett, N.L., Clements, L.S., Maeda, N., Vanin, E.F., Carlson, D.M., and Smithies, O.: Clones for the human gene complex coding for salivary prolinerich proteins. Proc Natl Acad Sci USA 81: 5561–5565, 1984.
Azen, E.A., Kim, H.S., Goodman, P., Flynn, S., and Maeda, N.: Alleles at the PRH1 locus coding for the human salivary acidic proline-rich proteins Pa, Db and PIF. Am J Hum Genet 41: 1035–1047, 1987.
Azen, E.A., Hellekant, G., Sabatini, L.M., and Warner, T.F.: mRNAs for PRPs, statherin and histatins in von Ebner's gland tissues. J Dental Res 69 1724–1730, 1990.
Bennick, A.: Salivary proline-rich proteins. Mol Cell Biochem 45: 83–99, 1982.
Bennick, A., Chau, G., Goodlin, R., Abrams, S., Tustian, D., and Madapallimattam, G.: The role of human salivary acidic prolinerich proteins in the formation of acquired dental pellicle in vivo and their fate after adsorption to the human enamel surface. Arch Oral Biol 28: 19–27, 1983.
Chang, L.-Y.E. and Slightom, J.L.: Isolation and nucleotide sequence analysis of the beta-type globin pseudogene from human, gorilla and chimpanzee. J Mol Biol 180: 767–784, 1984.
Chen, E.Y., Liao, Y.-C., Smith, D.H., Barrera-Saldana, H.A., Gelinas, R.E., and Seeburg, P.H.: The human growth hormone locus: nucleotide sequence, biology, and evolution. Genomics 4: 479–497, 1989.
Dale, R.M.K., McClure, B.A., and Houchins, J.P.: A rapid single-stranded cloning strategy for producing a sequential series of overlapping clones for use in DNA sequencing: application to sequencing the corn mitochondrial 18S rDNA. Plasmid 13: 31–40, 1985.
Devereux, J., Haberli, P., and Smithies, O.: A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res 12: 387–395, 1984.
Efstratiadis, A., Posakony, J.W., Maniatis, T., Lawn, R.M., O'Connell, C., Spritz, R.A., DeRiel, J.K., Forget, B.G., Weissman, S.M., Slightom, J.L., Blechl, A.E., Smithies, O., Baralle, F.E., Shoulders, C.C., and Proudfoot, N.J.: The structure and evolution of the human beta-globin gene family. Cell 21: 653–658, 1980.
Fitch, W.M. and Margoliash, E.: Construction of phylogenetic trees. Science 155: 279–284, 1967.
Gibbons, R.J. and Hay, D.I.: Human salivary acidic proline-rich proteins and statherin promote the attachment of Actinomyces viscosus LY7 to apathetic surfaces. Infect Immun 56: 439–445, 1980.
Hagerman, A.E. and Butler, L.G.: The specificity of proanthocyanidin-protein interactions. J Biol Chem 256: 4494–4497, 1981.
Hatton, M.N., Loomis, R.E., Levine, M.J., and Tabak, L.A.: Masticatory lubrication. The role of carbohydrate in the lubricating property of a salivary glycoprotein-albumin complex. Biochem J 230: 817–820, 1985.
Hood, L., Kronenberg, M., and Hunkapiller, T.: T cell antigen receptors and the immunoglobulin supergene family. Cell 40: 225–229, 1985.
Ito, S., Suzuki, T., Momotsu, T., Isemura, S., Saitoh, E., Sanada, K., and Shibata, A.: Presence of salivary protein C and salivary protein C and salivary peptide P-C like immunoreactivity in the laryngo-tracheo-bronchial glands. Acta Endocrinol 108: 130–134, 1985.
Kim, H.S. and Maeda, N.: Structure of two HaeIII-type genes in the human salivary proline-rich protein multigene family. J Biol Chem 261: 6712–6718, 1986.
Kim, H.S., Smithies, O., and Maeda, N.: A physical map of the human salivary proline-rich protein gene cluster covers over 700 kbp of DNA. Genomics 6: 260–267, 1990.
Kousvelari, E.E., Baratz, R.S., Burke, B., and Oppenheim, F.G.: Immunological identification and determination of proline-rich proteins in salivary secretions, enamel pellicle, and glandular tissue specimens. J Dent Res 59: 1430–1438, 1980.
Loenen, W.A.M. and Blattner, F.R.: Lambda Charon vectors (Ch 32, 33 and 35) adapted for DNA cloning in recombination-deficient hosts. Gene 26: 171–179, 1983.
Lyons, K.M., Azen, E.A., Goodman, P.A., and Smithies, O.: Many protein products from a few loci: assignment of human salivary proline-rich proteins to specific loci. Genetics 120: 255–265, 1988a.
Lyons, K.M., Stein, J.H., and Smithies, O.: Length polymorphisms in human proline-rich protein genes generated by intragenic unequal crossingover. Genetics 120: 267–278, 1988b.
Maeda, N.: Inheritance of the human salivary proline-rich proteins: a reinterpretation in terms of six foci forming two subfamilies. Biochem Genet 23: 455–464, 1985.
Maeda, N. and Smithies, O.: The evolution of multigene families; human haptoglobin genes. Annu Rev Genet 20: 81–108, 1986.
Maeda, N., Bliska, J.B., and Smithies, O.: Recombination and balanced chromosome polymorphism suggested by DNA sequences 5′ to the human delta-globin gene. Proc Natl Acad Sci USA 80: 5012–5016, 1983.
Maeda, N., Kim, H.S., Azen, E.A., and Smithies, O.: Differential RNA splicing and post-translocational cleavages in the human salivary proline-rich protein gene system. J Biol Chem 260: 11123–11130, 1985.
Mamula, P.W., Heerma, N.A., Plamer, C.G., Lyons, K.M., and Karn, R.C.: Localization of the human salivary proteins complex (SPC) to chromosome band 12 p13.2. Cytogenet Cell Genet 39: 279–284, 1985.
Maxam, A.M. and Gilbert, W.: A new method for sequencing DNA. Proc Natl Acad Sci USA 74: 560–564, 1977.
Minaguchi, K. and Bennick, A.: Genetics of human salivary proteins. J Dent Res 68: 2–15, 1989.
Moreno, E.C., Varughese, K., and Hay, D.I.: Effect of human salivary proteins on the precipitation kinetics of calcium phosphate. Calcif Tissue Int 28: 7–16, 1979.
Pustell, J., Kafatos, F.C., Wobus, U., and Baumlein, H.: Balbiani ring DNA: sequence comparisons and evolutionary history of a family of hierarchically repetitive protein-coding genes. J Mol Evol 20: 281–295, 1984.
Rimm, D.L., Horness, D., Ducera, J., and Blattner, F.R.: Construction of coliphage lambda Charon vectors with BamHI cloning sites. Gene 12: 301–309, 1980.
Sanger, T., Nicklen, S., and Coulson, A.R.: DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467, 1977.
Slightom, J.L., Blechl, A.E., and Smithies, O.: Human fetal G- and A-globin genes; complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell 21: 627–638, 1980.
Slightom, J.L., Theisen, T.W., Koop, B.F., and Goodman, M.: Orangutan fetal globin genes: nucleotide sequences reveal multiple gene conversions during hominid phylogeny. J Biol Chem 262: 7472–7483, 1987.
Warner, T.F. and Azen, E.A.: Proline-rich proteins are present in serous cells of submucosal glands in the respiratory tract. Am Rev Respir Dis 130: 115–118, 1984.
Saye, J.S. and Willard, H.F.: Structure, organization and sequence of alpha satellite DNA from human chromosome 17: evidence for evolution by unequal cross-over and an ancestral pentamer repeat share with the human X chromosome. Mol Cell Biol 6: 3156–3165, 1986.
Wong, R.S.C., Madapallimattam, G., and Bennick, A.: The role of glandular kallikrein in the formation of a salivary proline-rich protein A by cleavage of a single bond in salivary protein C. Biochem J 211: 35–44, 1983.
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Kim, H.S., Lyons, K.M., Saitoh, E. et al. The structure and evolution of the human salivary proline-rich protein gene family. Mammalian Genome 4, 3–14 (1993). https://doi.org/10.1007/BF00364656
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DOI: https://doi.org/10.1007/BF00364656