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Cited by 314Bone and Dental Protein Studiesdental development and anomaliesEvolution and Paleontology Studies

Mineralized tissue and vertebrate evolution: The secretory calcium-binding phosphoprotein gene cluster

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Kawasaki, Kazuhiko, Weiss, Kenneth M.·2003·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.0638023100PMC PMC153048
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Abstract

Gene duplication creates evolutionary novelties by using older tools in new ways. We have identified evidence that the genes for enamel matrix proteins (EMPs), milk caseins, and salivary proteins comprise a family descended from a common ancestor by tandem gene duplication. These genes remain linked, except for one EMP gene, amelogenin. These genes show common structural features and are expressed in ontogenetically similar tissues. Many of these genes encode secretory Ca-binding phosphoproteins, which regulate the Ca-phosphate concentration of the extracellular environment. By exploiting this fundamental property, these genes have subsequently diversified to serve specialized adaptive functions. Casein makes milk supersaturated with Ca-phosphate, which was critical to the successive mammalian divergence. The innovation of enamel led to mineralized feeding apparatus, which enabled active predation of early vertebrates. The EMP genes comprise a subfamily not identified previously. A set of genes for dentine and bone extracellular matrix proteins constitutes an additional cluster distal to the EMP gene cluster, with similar structural features to EMP genes. The duplication and diversification of the primordial genes for enamel/dentine/bone extracellular matrix may have been important in core vertebrate feeding adaptations, the mineralized skeleton, the evolution of saliva, and, eventually, lactation. The order of duplication events may help delineate early events in mineralized skeletal formation, which is a major characteristic of vertebrates.

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  • All of these genes originate from tandem duplications of a common ancestor and are located in clusters on human chromosome 4.

    “All of these genes originate from tandem duplications of a common ancestor and are located in clusters on human chromosome 4 [99].”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [99]

    The Abstract says the enamel matrix, casein, and salivary protein genes descended from a common ancestor by tandem duplication. The Results locate a cluster on human chromosome 4q13 and a dentine/bone gene cluster on 4q21, but also place amelogenin (AMEL) on the X and Y chromosomes. Thus, the claim's assertion that all the genes are clustered on chromosome 4 omits an explicit exception. (LLM, conf=0.91)

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  • Mammalian casein genes are thought to have originally arisen by duplication of either enamelin or ameloblastin.

    “Mammalian casein genes are thought to have originally arisen by duplication of either enamelin or ameloblastin 44 , both of which are tooth enamel matrix protein genes that are located adjacent to the casein gene cluster in eutherians and, we find, also in platypus.”

    From Genome analysis of the platypus reveals unique signatures of evolution (2008) · cites this paper as [44]

    The Results (page not specified) conclude that the ancestral calcium-sensitive casein gene probably derived from enamelin or ameloblastin, and the Discussion repeats that proposed origin. The claim says mammalian casein genes generally; the paper does not establish that origin for calcium-insensitive κ-casein. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Caseins belong to the SCPP family, which also includes enamel proteins such as amelogenin (AMEL), ameloblastin (AMBN), and enamelin (ENAM).

    “Caseins belong to the SCPP (secretory calcium-binding phosphoprotein) family, which also includes enamel proteins such as amelogenin (AMEL), ameloblastin (AMBN), and enamelin (ENAM).”

    From Origin and Evolution of Genes in Eukaryotes: Mechanisms, Dynamics, and Functional Implications (2025) · cites this paper as [99]

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Authors
Kawasaki, K., & Weiss, K. M.
Affiliations
Pennsylvania State University (US)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2003-03-19
Volume
100
Issue
7
Pages
4060-4065
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.0638023100
PMC
PMC153048
OpenAlex
W2099245827
Cited by
314
References
68
Citations by year
2026: 5 · 2025: 8 · 2024: 12 · 2023: 13 · 2022: 11 · 2021: 13 · 2020: 13 · 2019: 14 · 2018: 6 · 2017: 15 · 2016: 10 · 2015: 19 · 2014: 15 · 2013: 22 · 2012: 14
FWCI
8.37
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › dental development and anomalies
  • Physical Sciences › Earth and Planetary Sciences › Paleontology › Evolution and Paleontology Studies
Keywords
enamel matrix proteins, gene duplication, tandem gene duplication, amelogenin, milk casein, salivary proteins, extracellular matrix proteins, dentin, bone matrix, vertebrate evolution, feeding adaptation
MeSH terms
Animals, Bone Development, Calcium-Binding Proteins, Dental Enamel, Female, Multigene Family, Humans, Milk, Phosphoproteins, Phylogeny, Saliva, Vertebrates, Extracellular Matrix Proteins, Evolution, Molecular

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