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<p>The epithelial sodium channel (ENaC) is essential for osmoregulation in tetrapod vertebrates. There are four ENaC-subunits (α, β, γ, δ) which form αβγ- or δβγ-ENaCs. While αβγ-ENaC is a ‘maintenance protein’ controlling sodium homeostasis, δβγ-ENaC might represent a ‘stress protein’ monitoring high sodium concentrations. The δ-subunit emerged with water-to-land transition of vertebrates. We examined ENaC evolution in Cetartiodactyla, a group including even-toed ungulates and cetaceans (whales, dolphins and porpoises) which returned to marine environments in the Eocene. Genes for α-, β-, and γ-ENaC are intact across Cetartiodactyla. While <i>SCNN1D</i> (δ-ENaC) is intact in terrestrial Artiodactyla, it is a pseudogene in cetaceans. A unique fusion of <i>SCNN1D</i> exons 11 and 12 is observed in the Antilopinae. Transcripts of α-, β-, and γ-ENaC are present in kidney, lung and skin tissues of Bottlenose dolphins, underscoring αβγ-ENaC’s maintenance role. Bottlenose dolphins and Beluga whales do not show behavioural differences between sodium-containing and sodium-free stimuli, supporting a function of δ-ENaC as a sodium sensing protein which might have become obsolete in high-salinity marine environments. Consistently, there is reduced selection pressure or pseudogenisation of <i>SCNN1D</i> in other marine mammals. Erosion of <i>SCNN1D</i> might therefore be a consequence of environmental transition in marine mammals.</p><p></p>

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The evolutionary path of the epithelial sodium channel δ-subunit in Cetartiodactyla points to a role in sodium sensing

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月4日

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  • Fynn Zahnow,
  • Chiara Jäger,
  • Yassmin Mohamed,
  • Gianluca Vogelhuber,
  • Fabian May,
  • Alexandra Maria Ciocan,
  • Arianna Manieri,
  • Stephan Maxeiner,
  • Gabriela Krasteva-Christ,
  • Oskar Schnappauf,
  • Matthew R. D. Cobain,
  • Lars Podsiadlowski,
  • José Luis Crespo-Picazo,
  • Daniel García-Párraga,
  • Mike Althaus

摘要

The epithelial sodium channel (ENaC) is essential for osmoregulation in tetrapod vertebrates. There are four ENaC-subunits (α, β, γ, δ) which form αβγ- or δβγ-ENaCs. While αβγ-ENaC is a ‘maintenance protein’ controlling sodium homeostasis, δβγ-ENaC might represent a ‘stress protein’ monitoring high sodium concentrations. The δ-subunit emerged with water-to-land transition of vertebrates. We examined ENaC evolution in Cetartiodactyla, a group including even-toed ungulates and cetaceans (whales, dolphins and porpoises) which returned to marine environments in the Eocene. Genes for α-, β-, and γ-ENaC are intact across Cetartiodactyla. While SCNN1D (δ-ENaC) is intact in terrestrial Artiodactyla, it is a pseudogene in cetaceans. A unique fusion of SCNN1D exons 11 and 12 is observed in the Antilopinae. Transcripts of α-, β-, and γ-ENaC are present in kidney, lung and skin tissues of Bottlenose dolphins, underscoring αβγ-ENaC’s maintenance role. Bottlenose dolphins and Beluga whales do not show behavioural differences between sodium-containing and sodium-free stimuli, supporting a function of δ-ENaC as a sodium sensing protein which might have become obsolete in high-salinity marine environments. Consistently, there is reduced selection pressure or pseudogenisation of SCNN1D in other marine mammals. Erosion of SCNN1D might therefore be a consequence of environmental transition in marine mammals.