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