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PTH Reloaded: A New Evolutionary Perspective.

Paula Suarez-Bregua1, Laura Cal1, Cristian Cañestro2

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|October 25, 2017
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The parathyroid hormone (PTH) family, crucial for bone health, has evolved diverse roles in vertebrates. This study proposes a new PTH nomenclature and explores brain-to-bone signaling in fish, offering insights into vertebrate evolution.

Keywords:
GPCRPTH familyPth4bone homeostasisevolutionfishmineral balanceohnologs

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Area of Science:

  • Evolutionary Biology
  • Endocrinology
  • Comparative Genomics

Background:

  • The parathyroid hormone (PTH) and PTH receptor (PTHR) signaling pathway is vital for bone mineral homeostasis and vertebrate development.
  • These genes are found in chordates, suggesting an evolutionary origin within this phylum.
  • Vertebrates exhibit varied numbers of PTH and PTHR paralogs due to genome duplication and gene loss events.

Purpose of the Study:

  • To review the roles of PTH peptides in fishes.
  • To propose a new nomenclature (PTH1-PTH4) for PTH paralogs based on evolutionary history.
  • To discuss the evolutionary model of PTH functions during the vertebrate transition from aquatic to terrestrial environments.

Main Methods:

  • Comparative analysis of PTH and PTHR gene families across vertebrates.
  • Review of existing literature on fish PTH peptide functions.
  • Phylogenetic analysis to establish evolutionary relationships.

Main Results:

  • Identified up to six PTH and three PTHR paralogs in vertebrates, with variations between mammals and teleost fishes.
  • Proposed a new, simplified nomenclature for PTH peptides (PTH1-PTH4).
  • Highlighted the role of Pth4 in zebrafish, emphasizing brain-to-bone signaling in bone development.

Conclusions:

  • The PTH signaling system has undergone significant diversification and functional adaptation throughout vertebrate evolution.
  • The proposed nomenclature facilitates clearer communication and comparison of PTH functions across species.
  • Understanding PTH evolution provides insights into bone mineral balance adaptations during vertebrate terrestrialization.