Skip to main content
Article
Licensed
Unlicensed Requires Authentication

Evolution of Klk4 and enamel maturation in eutherians

  • , and EMAIL logo
Published/Copyright: August 6, 2014
Biological Chemistry
From the journal Biological Chemistry Volume 395 Issue 9

Abstract

Kallikrein-related peptidase 4 (KLK4) is a secreted serine protease that degrades residual enamel proteins to facilitate their removal by ameloblasts, which increases mineralization and hardens the enamel. Mutations in human KLK4 cause hypomaturation amelogenesis imperfecta. Enamel formed by Klk4 null mice is normal in thickness and prism structure, but the enamel layer retains proteins, is hypomineralized, and undergoes rapid attrition following tooth eruption. We searched multiple databases, retrieved Klk4 and Klk5 from various mammalian genomes, and identified Klk4 in 46 boreoeutherian genomes. In non-Boreoeutheria, Klk4 was detected in only one afrotherian genome (as a pseudogene), and not in the other six afrotherian, two xenarthran, or three marsupial genomes. In contrast, Klk5 was detected in both marsupial and eutherian mammals. Our phylogenetic and mutation rate analyses support the hypothesis that Klk4 arose from Klk5 by gene duplication near the divergence of Afrotheria, Xenarthra and Boreoeutheria, and that functionally-differentiated Klk4 survived only in Boreoeutheria. Afrotherian mammals share the feature of delayed dental eruption relative to boreoeutherian mammals. KLK4 shortens the time required for enamel maturation and could have alleviated negative selection following mutations that resulted in thicker enamel or earlier tooth eruption, without reducing enamel hardness or causing dental attrition.

Keywords: Afrotheria; enamel; kallikrein-related peptidase 4; protease; tooth eruption
Corresponding author: James P. Simmer, Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, 1210 Eisenhower Place, Ann Arbor, MI 48108, USA, e-mail:

Acknowledgments

This investigation was supported by USPHS Research Grant DE019775 from the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 29892 and National Science Foundation grants BCS0725227 and BCS0343442.

References

Asher, R.J. and Lehmann, T. (2008). Dental eruption in afrotherian mammals. BMC Biol. 6, 14.10.1186/1741-7007-6-14Search in Google Scholar

Barry, J.C. and Kemp, A. (2007). High resolution transmission electron microscopy of developing enamel in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi). Tissue Cell. 39, 387–398.10.1016/j.tice.2007.07.001Search in Google Scholar

Deakins, M. and Volker, J.F. (1941). Amount of organic matter in enamel from several types of human teeth. J. Dent. Res. 20, 117–121.10.1177/00220345410200020201Search in Google Scholar

Debela, M., Magdolen, V., Schechter, N., Valachova, M., Lottspeich, F., Craik, C.S., Choe, Y., Bode, W., and Goettig, P. (2006). Specificity profiling of seven human tissue kallikreins reveals individual subsite preferences. J. Biol. Chem. 281, 25678–88.10.1074/jbc.M602372200Search in Google Scholar

Debela, M., Goettig, P., Magdolen, V., Huber, R., Schechter, N.M., and Bode, W. (2007). Structural basis of the zinc inhibition of human tissue kallikrein 5. J. Mol. Biol. 373, 1017–31.10.1016/j.jmb.2007.08.042Search in Google Scholar

Debela, M., Beaufort, N., Magdolen, V., Schechter, N.M., Craik, C.S., Schmitt, M., Bode, W., and Goettig, P. (2008). Structures and specificity of the human kallikrein-related peptidases KLK 4, 5, 6, and 7. Biol. Chem. 389, 623–32.10.1515/BC.2008.075Search in Google Scholar

Elliott, M.B., Irwin, D.M., and Diamandis, E.P. (2006). In silico identification and Bayesian phylogenetic analysis of multiple new mammalian kallikrein gene families. Genomics 88, 591–599.10.1016/j.ygeno.2006.06.001Search in Google Scholar

Fukae, M. and Shimizu, M. (1974). Studies on the proteins of developing bovine enamel. Arch. Oral Biol. 19, 381–386.10.1016/0003-9969(74)90179-4Search in Google Scholar

Gu, X. (1999). Statistical methods for testing functional divergence after gene duplication. Mol. Biol. Evol. 16, 1664–1674.10.1093/oxfordjournals.molbev.a026080Search in Google Scholar PubMed

Gu, X. (2006). A simple statistical method for estimating type-II (cluster-specific) functional divergence of protein sequences. Mol. Biol. Evol. 23, 1937–1945.10.1093/molbev/msl056Search in Google Scholar PubMed

Hart, P.S., Hart, T.C., Michalec, M.D., Ryu, O.H., Simmons, D., Hong, S., and Wright, J.T. (2004). Mutation in kallikrein 4 causes autosomal recessive hypomaturation amelogenesis imperfecta. J. Med. Genet. 41, 545–549.10.1136/jmg.2003.017657Search in Google Scholar

Hu, J.C., Zhang, C., Sun, X., Yang, Y., Cao, X., Ryu, O., and Simmer, J.P. (2000). Characterization of the mouse and human PRSS17 genes, their relationship to other serine proteases, and the expression of PRSS17 in developing mouse incisors. Gene 251, 1–8.10.1016/S0378-1119(00)00203-1Search in Google Scholar

Hu, J.C., Sun, X., Zhang, C., Liu, S., Bartlett, J.D., and Simmer, J.P. (2002). Enamelysin and kallikrein-4 mRNA expression in developing mouse molars. Eur. J. Oral Sci. 110, 307–315.10.1034/j.1600-0722.2002.21301.xSearch in Google Scholar PubMed

Hu, Y., Hu, J.C., Smith, C.E., Bartlett, J.D., and Simmer, J.P. (2011). Kallikrein-related peptidase 4, matrix metalloproteinase 20, and the maturation of murine and porcine enamel. Eur. J. Oral Sci. 119, 217–25.10.1111/j.1600-0722.2011.00859.xSearch in Google Scholar PubMed PubMed Central

Kawasaki, K. (2011). The SCPP gene family and the complexity of hard tissues in vertebrates. Cells Tissues Organs 194, 108–112.10.1159/000324225Search in Google Scholar PubMed

Kawasaki, K. and Amemiya, C. (2013). SCPP genes in the coelacanth: Tissue mineralization genes shared by sarcopterygians. J. Exp. Zool. (Mol. Dev. Evol.) 9999B, 1–13.Search in Google Scholar

Kawasaki, K. and Suzuki, T. (2011). Molecular evolution of matrix metalloproteinase 20. Eur. J. Oral Sci. 119, 247–253.10.1111/j.1600-0722.2011.00898.xSearch in Google Scholar PubMed

Klein, S.L., Strausberg, R.L., Wagner, L., Pontius, J., Clifton, S.W., and Richardson, P. (2002). Genetic and genomic tools for Xenopus research: The NIH Xenopus initiative. Dev. Dyn. 225, 384–391.10.1002/dvdy.10174Search in Google Scholar PubMed

Koumandou, V.L. and Scorilas, A. (2013). Evolution of the plasma and tissue kallikreins, and their alternative splicing isoforms. PLoS One. 8, e68074.10.1371/journal.pone.0068074Search in Google Scholar PubMed PubMed Central

Le, S.Q. and Gascuel, O. (2008). An improved general amino acid replacement matrix. Mol. Biol. Evol. 25, 1307–1320.10.1093/molbev/msn067Search in Google Scholar PubMed

Lu, Y., Papagerakis, P., Yamakoshi, Y., Hu, J.C., Bartlett, J.D., and Simmer, J.P. (2008). Functions of KLK4 and MMP-20 in dental enamel formation. Biol. Chem. 389, 695–700.10.1515/BC.2008.080Search in Google Scholar PubMed PubMed Central

Lundwall, A. (2013). Old genes and new genes: the evolution of the kallikrein locus. Thromb. Haemost. 110, 469–475.10.1160/TH12-11-0851Search in Google Scholar PubMed

Madsen, O. 2009. Mammals (Mammalia). In The timetree of life. S.B. Hedges and S. Kumar, editors. Oxford University Press, New York. 459–461.Search in Google Scholar

Meredith, R.W., Gatesy, J., Murphy, W.J., Ryder, O.A., and Springer, M.S. (2009). Molecular decay of the tooth gene Enamelin (ENAM) mirrors the loss of enamel in the fossil record of placental mammals. PLoS Genet. 5, e1000634.10.1371/journal.pgen.1000634Search in Google Scholar PubMed PubMed Central

Meredith, R.W., Gatesy, J., Cheng, J., and Springer, M.S. (2011a). Pseudogenization of the tooth gene enamelysin (MMP20) in the common ancestor of extant baleen whales. Proc. Biol. Sci. 278, 993–1002.10.1098/rspb.2010.1280Search in Google Scholar PubMed PubMed Central

Meredith, R.W., Janecka, J.E., Gatesy, J., Ryder, O.A., Fisher, C.A., Teeling, E.C., Goodbla, A., Eizirik, E., Simao, T.L., Stadler, T., et al. (2011b). Impacts of the Cretaceous Terrestrial Revolution and KPg extinction on mammal diversification. Science. 334, 521–4.10.1126/science.1211028Search in Google Scholar PubMed

Meredith, R.W., Gatesy, J., and Springer, M.S. (2013). Molecular decay of enamel matrix protein genes in turtles and other edentulous amniotes. BMC Evol. Biol. 13, 20.10.1186/1471-2148-13-20Search in Google Scholar PubMed PubMed Central

Murphy, W., and Eizirik, E. (2009). Placental mammals (Eutheria). In: The Timetree of Life, S.B. Hedges, S. Kumar, editors. New York: Oxford University Press, pp. 471–474.Search in Google Scholar

Nagano, T., Kakegawa, A., Yamakoshi, Y., Tsuchiya, S., Hu, J.C., Gomi, K., Arai, T., Bartlett, J.D., and Simmer, J.P. (2009). Mmp-20 and Klk4 cleavage site preferences for amelogenin sequences. J. Dent. Res. 88, 823–828.10.1177/0022034509342694Search in Google Scholar PubMed PubMed Central

Nanci, A. (2003). Enamel: composition, formation, and structure. In: Ten Cate’s Oral Histology Development, Structure, and Function, A. Nanci, ed. (St. Louis, MO: Mosby), pp. 145–191.Search in Google Scholar

Nei, M. (1987). Molecular evolutionary genetics New York: Columbia Univ. Press.Search in Google Scholar

Nei, M. and Kumar, S. (2000). Molecular Evolution and Phylogenetics (New York, NY: Oxford University Press).Search in Google Scholar

Newbrun, E. and Pigman, W. (1960). The hardness of enamel and dentine. Aust. Dent. J. 5, 210–217.10.1111/j.1834-7819.1960.tb01939.xSearch in Google Scholar

Nishihara, H., Maruyama, S., and Okada, N. (2009). Retroposon analysis and recent geological data suggest near-simultaneous divergence of the three superorders of mammals. Proc. Natl. Acad. Sci. USA. 106, 5235–40.10.1073/pnas.0809297106Search in Google Scholar PubMed PubMed Central

Notredame, C. (2010). Computing multiple sequence/structure alignments with the T-coffee package. Curr. Protoc. Bioinformatics. Chapter, Unit 3.8.1–25.10.1002/0471250953.bi0308s29Search in Google Scholar PubMed

O’Leary, M.A., Bloch, J.I., Flynn, J.J., Gaudin, T.J., Giallombardo, A., Giannini, N.P., Goldberg, S.L., Kraatz, B.P., Luo, Z.X., Meng, J., et al. (2013). The placental mammal ancestor and the post-K-Pg radiation of placentals. Science. 339, 662–7.10.1126/science.1229237Search in Google Scholar PubMed

Ohno, S. (1970). Evolution by Gene Duplication (New York, NY: Springer).10.1007/978-3-642-86659-3Search in Google Scholar

Parry, M.A., Fernandez-Catalan, C., Bergner, A., Huber, R., Hopfner, K.P., Schlott, B., Gührs, K.H., and Bode, W. (1998). The ternary microplasmin-staphylokinase-microplasmin complex is a proteinase-cofactor-substrate complex in action. Nat. Struct. Biol. 5, 917–923.10.1038/2359Search in Google Scholar PubMed

Pavlopoulou, A., Pampalakis, G., Michalopoulos, I., and Sotiropoulou, G. (2010). Evolutionary history of tissue kallikreins. PLoS One 5, e13781.10.1371/journal.pone.0013781Search in Google Scholar PubMed PubMed Central

Romiguier, J., Ranwez, V., Delsuc, F., Galtier, N., and Douzery, E.J. (2013). Less is more in mammalian phylogenomics: AT-rich genes minimize tree conflicts and unravel the root of placental mammals. Mol. Biol. Evol. 30, 2134–44.10.1093/molbev/mst116Search in Google Scholar PubMed

Ryu, O.H., Hu, C.C., Zhang, C., Qian, Q., Moradian-Oldak, J., Fincham, A.G., and Simmer, J.P. (1998). Proteolytic activity of opossum tooth extracts. Eur. J. Oral Sci. 106 (Suppl 1), 337–344.10.1111/j.1600-0722.1998.tb02195.xSearch in Google Scholar PubMed

Ryu, O., Hu, J.C., Yamakoshi, Y., Villemain, J.L., Cao, X., Zhang, C., Bartlett, J.D., and Simmer, J.P. (2002). Porcine kallikrein-4 activation, glycosylation, activity, and expression in prokaryotic and eukaryotic hosts. Eur. J. Oral Sci. 110, 358–365.10.1034/j.1600-0722.2002.21349.xSearch in Google Scholar PubMed

Satchell, P.G., Shuler, C.F., and Diekwisch, T.G. (2000). True enamel covering in teeth of the Australian lungfish Neoceratodus forsteri. Cell Tissue Res. 299, 27–37.10.1007/s004410050003Search in Google Scholar

Simmer, J.P., Hu, Y., Lertlam, R., Yamakoshi, Y., and Hu, J.C. (2009). Hypomaturation enamel defects in Klk4 knockout/LacZ knockin mice. J. Biol. Chem. 284, 19110–19121.10.1074/jbc.M109.013623Search in Google Scholar PubMed PubMed Central

Simmer, J., Hu, Y., Richardson, A., Bartlett, J., and Hu, J.C.-C. (2011a). Why does enamel in Klk4 null mice break above the dentino-enamel junction? Cells Tissues Organs 194, 211–215.10.1159/000324260Search in Google Scholar PubMed PubMed Central

Simmer, J.P., Richardson, A.S., Smith, C.E., Hu, Y., and Hu, J.C. (2011b). Expression of kallikrein-related peptidase 4 in dental and non-dental tissues. Eur. J. Oral Sci. 119, 226–233.10.1111/j.1600-0722.2011.00834.xSearch in Google Scholar PubMed PubMed Central

Smith, C.E. (1998). Cellular and chemical events during enamel maturation. Crit. Rev. Oral Biol. Med. 9, 128–161.10.1177/10454411980090020101Search in Google Scholar PubMed

Smith, C.E., Richardson, A.S., Hu, Y., Bartlett, J.D., Hu, J.C., and Simmer, J.P. (2011). Effect of Kallikrein 4 loss on enamel mineralization: comparison with mice lacking matrix metalloproteinase 20. J. Biol. Chem. 286, 18149–18160.10.1074/jbc.M110.194258Search in Google Scholar PubMed PubMed Central

Song, S., Liu, L., Edwards, S.V., and Wu, S. (2012). Resolving conflict in eutherian mammal phylogeny using phylogenomics and the multispecies coalescent model. Proc. Natl. Acad. Sci. USA. 109, 14942–7.10.1073/pnas.1211733109Search in Google Scholar PubMed PubMed Central

Springer, M.S., Meredith, R.W., Janecka, J.E., and Murphy, W.J. (2011). The historical biogeography of Mammalia. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 366, 2478–502.10.1098/rstb.2011.0023Search in Google Scholar PubMed PubMed Central

Tamura, K., Peterson, D., Peterson, N., Stecher, G., Nei, M., and Kumar, S. (2011). MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol. Biol. Evol. 28, 2731–2739.10.1093/molbev/msr121Search in Google Scholar PubMed PubMed Central

Tamura, K., Stecher, G., Peterson, D., Filipski, A., and Kumar, S. (2013). MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol. Biol. Evol. 30, 2725–2729.10.1093/molbev/mst197Search in Google Scholar PubMed PubMed Central

Wang, Y. and Gu, X. (2001). Functional divergence in the caspase gene family and altered functional constraints: statistical analysis and prediction. Genetics 158, 1311–1320.10.1093/genetics/158.3.1311Search in Google Scholar PubMed PubMed Central

Wang, S.K., Hu, Y., Simmer, J.P., Seymen, F., Estrella, N.M., Pal, S., Reid, B.M., Yildirim, M., Bayram, M., Bartlett, J.D., et al. (2013). Novel KLK4 and MMP20 mutations discovered by whole-exome sequencing. J. Dent. Res. 92, 266–271.10.1177/0022034513475626Search in Google Scholar PubMed PubMed Central

Wildman, D.E., Uddin, M., Opazo, J.C., Liu, G., Lefort, V., Guindon, S., Gascuel, O., Grossman, L.I., Romero, R., and Goodman, M. (2007). Genomics, biogeography, and the diversification of placental mammals. Proc. Natl. Acad. Sci. USA. 104, 14395–400.10.1073/pnas.0704342104Search in Google Scholar PubMed PubMed Central

Wilson, D., and Reeder, D. (2005). Mammal species of the world. 3rd ed. Baltimore: John Hopkins Univ. Press.10.56021/9780801882210Search in Google Scholar

Wong, M.K. and Takei, Y. (2013). Lack of plasma kallikrein-kinin system cascade in teleosts. PLoS One 8, e81057.10.1371/journal.pone.0081057Search in Google Scholar PubMed PubMed Central

Yamakoshi, Y., Richardson, A.S., Nunez, S.M., Yamakoshi, F., Milkovich, R.N., Hu, J.C., Bartlett, J.D., and Simmer, J.P. (2011). Enamel proteins and proteases in Mmp20 and Klk4 null and double-null mice. Eur. J. Oral Sci. 119, 206–216.10.1111/j.1600-0722.2011.00866.xSearch in Google Scholar PubMed PubMed Central

Yousef, G.M., Chang, A., Scorilas, A., and Diamandis, E.P. (2000). Genomic organization of the human kallikrein gene family on chromosome 19q13.3-q13.4. Biochem. Biophys. Res. Commun. 276, 125–133.10.1006/bbrc.2000.3448Search in Google Scholar PubMed

Supplemental Material

The online version of this article (DOI 10.1515/hsz-2014-0122) offers supplementary material, available to authorized users.

Received: 2014-3-7
Accepted: 2014-6-9
Published Online: 2014-8-6
Published in Print: 2014-9-1

©2014 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: The 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  4. KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family
  5. Putative kallikrein substrates and their (patho)biological functions
  6. Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy
  7. Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity
  8. Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases
  9. Kallikreins are involved in an miRNA network that contributes to prostate cancer progression
  10. Evolution of Klk4 and enamel maturation in eutherians
  11. Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor
  12. CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation
  13. Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences
  14. Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma
  15. Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response
  16. Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer
  17. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer
  18. Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients
  19. Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
  20. Development of monoclonal antibodies to human kallikrein-related peptidase 6 (KLK6) and their use in an immunofluorometric assay for free KLK6
  21. Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
https://doi.org/10.1515/hsz-2014-0122
Keywords for this article
Afrotheria; enamel; kallikrein-related peptidase 4; protease; tooth eruption

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: The 5th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  4. KLKs and their hormone-like signaling actions: a new life for the PSA-KLK family
  5. Putative kallikrein substrates and their (patho)biological functions
  6. Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy
  7. Sweetened kallikrein-related peptidases (KLKs): glycan trees as potential regulators of activation and activity
  8. Activation of membrane-bound proteins and receptor systems: a link between tissue kallikrein and the KLK-related peptidases
  9. Kallikreins are involved in an miRNA network that contributes to prostate cancer progression
  10. Evolution of Klk4 and enamel maturation in eutherians
  11. Growth and survival of lung cancer cells: regulation by kallikrein-related peptidase 6 via activation of proteinase-activated receptor 2 and the epidermal growth factor receptor
  12. CrataBL, a lectin and Factor Xa inhibitor, plays a role in blood coagulation and impairs thrombus formation
  13. Mining for single nucleotide variants (SNVs) at the kallikrein locus with predicted functional consequences
  14. Low mRNA expression levels of kallikrein-related peptidase 4 (KLK4) predict short-term relapse in patients with laryngeal squamous cell carcinoma
  15. Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response
  16. Kallikrein-related peptidase 7 (KLK7) is a proliferative factor that is aberrantly expressed in human colon cancer
  17. Prognostic significance of human tissue kallikrein-related peptidases 6 and 10 in gastric cancer
  18. Loss of miR-378 in prostate cancer, a common regulator of KLK2 and KLK4, correlates with aggressive disease phenotype and predicts the short-term relapse of the patients
  19. Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma
  20. Development of monoclonal antibodies to human kallikrein-related peptidase 6 (KLK6) and their use in an immunofluorometric assay for free KLK6
  21. Analysis of androgen and anti-androgen regulation of KLK-related peptidase 2, 3, and 4 alternative transcripts in prostate cancer
Downloaded on 1.5.2026 from https://www.degruyterbrill.com/document/doi/10.1515/hsz-2014-0122/html?lang=en
Scroll to top button