TY  - INPR
U1  - Preprint
A1  - Zahnow, Fynn
A1  - Jaeger, Chiara
A1  - Mohamed, Yassmin
A1  - Vogelhuber, Gianluca
A1  - May, Fabian
A1  - Ciocan, Alexandra Maria
A1  - Manieri, Arianna
A1  - Maxeiner, Stephan
A1  - Krasteva-Christ, Gabriela
A1  - Cobain, Matthew R.D.
A1  - Podsiadlowski, Lars
A1  - Crespo-Picazo, Jose Luis
A1  - Garcia-Parraga, Daniel
A1  - Althaus, Mike
T1  - The evolutionary path of the epithelial sodium channel delta-subunit in Cetartiodactyla points to a role in sodium sensing
T2  - bioRxiv
N2  - The epithelial sodium channel (ENaC) plays a key role in osmoregulation in tetrapod vertebrates and is a candidate receptor for salt taste sensation. There are four ENaC subunits (alpha, beta, gamma, & delta) which form alpha beta gamma or delta beta gamma-ENaCs. While alpha beta gamma-ENaC is a maintenance protein controlling sodium and potassium homeostasis, delta beta gamma-ENaC might represent a stress protein monitoring high sodium concentrations. The delta-subunit emerged with water-to-land transition of tetrapod vertebrate ancestors. We investigated the evolutionary path of ENaC-coding genes in Cetartiodactyla, a group comprising even-toed ungulates and the cetaceans (whales/dolphins) which transitioned from terrestrial to marine environments in the Eocene. The genes SCNN1A (alpha-ENaC), SCNN1B (beta-ENaC) and SCNN1G (gamma-ENaC) are intact in all 22 investigated cetartiodactylan families. While SCNN1D (delta-ENaC) is intact in terrestrial Artiodactyla, it is a pseudogene in 12 cetacean families. A fusion of SCNN1D exons 11 and 12 under preservation of the open reading frame was observed in the Antilopinae, representing a new feature of this clade. Transcripts of SCNN1A, SCNN1B and SCNN1G were present in kidney and lung tissues of Bottlenose dolphins, highlighting alpha beta gamma-ENaC's role as a maintenance protein. Consistent with SCNN1D loss, Bottlenose dolphins and Beluga whales did not show behavioural differences to stimuli with or without sodium in seawater-equivalent concentrations. These data suggest a function of delta-ENaC as a sodium sensing protein which might have become obsolete in cetaceans after the migration to high-salinity marine environments. Consistently, there is reduced selection pressure or pseudogenisation of SCNN1D in other marine mammals, including sirenians, pinnipeds and sea otter.
Y1  - 2024
U6  - https://doi.org/10.1101/2024.11.18.623996
DO  - https://doi.org/10.1101/2024.11.18.623996
PM  - 39605611
ER  -