Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions

Abstract Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already...

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Main Authors: Frantisek Spoutil, Goretti Aranaz-Novaliches, Michaela Prochazkova, Tomas Wald, Vendula Novosadova, Petr Kasparek, Radim Osicka, Janne E. Reseland, Staale P. Lyngstadaas, Hanna Tiainen, Kristyna Bousova, Jiri Vondrasek, Radislav Sedlacek, Jan Prochazka
Format: Article
Language:English
Published: Nature Portfolio 2023-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-28388-4
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author Frantisek Spoutil
Goretti Aranaz-Novaliches
Michaela Prochazkova
Tomas Wald
Vendula Novosadova
Petr Kasparek
Radim Osicka
Janne E. Reseland
Staale P. Lyngstadaas
Hanna Tiainen
Kristyna Bousova
Jiri Vondrasek
Radislav Sedlacek
Jan Prochazka
author_facet Frantisek Spoutil
Goretti Aranaz-Novaliches
Michaela Prochazkova
Tomas Wald
Vendula Novosadova
Petr Kasparek
Radim Osicka
Janne E. Reseland
Staale P. Lyngstadaas
Hanna Tiainen
Kristyna Bousova
Jiri Vondrasek
Radislav Sedlacek
Jan Prochazka
author_sort Frantisek Spoutil
collection DOAJ
description Abstract Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.
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spelling doaj.art-9cee86c6099c4e5593b71dbfde9ce7ab2023-01-29T12:11:59ZengNature PortfolioScientific Reports2045-23222023-01-0113111410.1038/s41598-023-28388-4Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functionsFrantisek Spoutil0Goretti Aranaz-Novaliches1Michaela Prochazkova2Tomas Wald3Vendula Novosadova4Petr Kasparek5Radim Osicka6Janne E. Reseland7Staale P. Lyngstadaas8Hanna Tiainen9Kristyna Bousova10Jiri Vondrasek11Radislav Sedlacek12Jan Prochazka13Czech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CASCzech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CASCzech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CASProgram in Craniofacial Biology and Department of Orofacial Sciences, University of CaliforniaCzech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CASCzech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CASLaboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the CASDepartment of Biomaterials, Institute of Clinical Dentistry, University of OsloDepartment of Biomaterials, Institute of Clinical Dentistry, University of OsloDepartment of Biomaterials, Institute of Clinical Dentistry, University of OsloInstitute of Organic Chemistry and Biochemistry of the CASInstitute of Organic Chemistry and Biochemistry of the CASCzech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CASCzech Centre for Phenogenomics and Laboratory of Transgenic Models of Diseases, Institute of Molecular Genetics of the CASAbstract Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.https://doi.org/10.1038/s41598-023-28388-4
spellingShingle Frantisek Spoutil
Goretti Aranaz-Novaliches
Michaela Prochazkova
Tomas Wald
Vendula Novosadova
Petr Kasparek
Radim Osicka
Janne E. Reseland
Staale P. Lyngstadaas
Hanna Tiainen
Kristyna Bousova
Jiri Vondrasek
Radislav Sedlacek
Jan Prochazka
Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions
Scientific Reports
title Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions
title_full Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions
title_fullStr Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions
title_full_unstemmed Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions
title_short Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions
title_sort early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions
url https://doi.org/10.1038/s41598-023-28388-4
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