Autor(es):
Pinheiro, Pedro L. C. 
; Cardoso, J. C. R. ; Gomes, Ana S. ; Fuentes, Juan ; Power, Deborah ; Canario, Adelino V. M.
Data: 2010
Identificador Persistente: http://hdl.handle.net/10400.1/5403
Origem: Sapientia - Universidade do Algarve
Assunto(s): Evolutionary Biology; Parathyroid hormone
Descrição
Background: Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) belong to a family of endocrine factors
that share a highly conserved N-terminal region (amino acids 1-34) and play key roles in calcium homeostasis,
bone formation and skeletal development. Recently, PTH-like peptide (PTH-L) was identified in teleost fish raising
questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in
mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique
phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to
homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation.
This study investigated PTH family evolution in vertebrates with special emphasis on Xenopus and chicken.
Results: The PTH-L gene is present throughout the vertebrates with the exception of placental mammals. Gene
structure of PTH and PTH-L seems to be conserved in vertebrates while PTHrP gene structure is divergent and has
acquired new exons and alternative promoters. Splice variants of PTHrP and PTH-L are common in Xenopus and
chicken and transcripts of the former have a widespread tissue distribution, although PTH-L is more restricted. PTH
is widely expressed in fish tissue but from Xenopus to mammals becomes largely restricted to the parathyroid
gland. The N-terminal (1-34) region of PTH, PTHrP and PTH-L in Xenopus and chicken share high sequence
conservation and the capacity to modify calcium fluxes across epithelia suggesting a conserved role in calcium
metabolism possibly via similar receptors.
Conclusions: The parathyroid hormone family contains 3 principal members, PTH, PTHrP and the recently
identified PTH-L. In teleosts there are 5 genes which encode PTHrP (2), PTH (2) and PTH-L and in tetrapods there
are 3 genes (PTHrP, PTH and PTH-L), the exception is placental mammals which have 2 genes and lack PTH-L. It is
hypothesized that genes of the PTH family appeared at approximately the same time during the vertebrate
radiation and evolved via gene duplication/deletion events. PTH-L was lost from the genome of eutherian
mammals and PTH, which has a paracrine distribution in lower vertebrates, became the product of a specific
endocrine tissue in Amphibia, the parathyroid gland. The PTHrP gene organisation diverged and became more
complex in vertebrates and retained its widespread tissue distribution which is congruent with its paracrine nature.
