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

## TL;DR

This study explores how the ENaC δ-subunit evolved in marine mammals, suggesting it became unnecessary due to high salt levels in their environment.

## Contribution

The paper reveals that the SCNN1D gene encoding the δ-subunit of ENaC is pseudogenized in marine mammals, indicating a loss of sodium sensing function.

## Key findings

- SCNN1D is a pseudogene in cetaceans but intact in terrestrial Artiodactyla.
- Bottlenose dolphins lack behavioral response to sodium stimuli, supporting δ-ENaC's role in sodium sensing.
- Reduced selection pressure on SCNN1D is observed in other marine mammals.

## Abstract

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.

Zahnow et al. investigate the evolution of epithelial sodium channels (ENaCs) in mammals returning to marine life. ENaCs are built of αβγ- or δβγ-subunits. Their study suggests the SCNN1D gene encoding the δ-subunit suffers pseudogenization events in marine mammals due to high-salinity environment.