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bioRxiv · 10.1101/2024.11.18.623996

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

Zahnow, F.·Jaeger, C.·Mohamed, Y.·Vogelhuber, G.·May, F.·Ciocan, A. M.·Manieri, A.·Maxeiner, S.·Krasteva-Christ, G.·Cobain, M. R. D.·Podsiadlowski, L.·Crespo-Picazo, J. L.·Garcia-Parraga, D.·Althaus, M.
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Abstract

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 (, {beta}, {gamma}, {delta}) which form {beta}{gamma}- or {delta}{beta}{gamma} ENaCs. While {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 (-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 {beta}{gamma}-ENaCs 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.

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Zahnow, F., Jaeger, C., Mohamed, Y., Vogelhuber, G., May, F., Ciocan, A. M., Manieri, A., Maxeiner, S., Krasteva-Christ, G., Cobain, M. R. D., Podsiadlowski, L., Crespo-Picazo, J. L., Garcia-Parraga, D., Althaus, M.. 2024-11-19. The evolutionary path of the epithelial sodium channel delta-subunit in Cetartiodactyla points to a role in sodium sensing. https://doi.org/10.1101/2024.11.18.623996

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