Independent Expansion of SLC7A3 in Mammals to Meet the Challenge of Nitrogen Metabolism

Abstract Adequate nitrogen metabolism is crucial for survival, yet carnivores and herbivores face distinct challenges: carnivores must efficiently detoxify ammonia, while herbivorous ruminants need to conserve and recycle nitrogen. Gene family expansion through duplication is a key evolutionary mechanism for adaptation. Here we show that the Cationic Amino Acid Transporter gene SLC7A3 has independently expanded via duplication in both ruminants (e.g., sheep, cattle) and carnivores to address their specific nitrogen balance pressures. These parallel expansions occurred at different, lineage-specific genomic locations. Following duplication, the SLC7A3 copies in carnivores underwent relaxed selection, whereas those in ruminants were under strong purifying selection. Expression analyses indicate high expression of these gene copies in intestines, blood, lungs, and spleen, suggesting a role in enhancing arginine transport to support urea cycle function. This study demonstrates convergent evolution through copy number variation, linking specific dietary challenges to large-scale genomic adaptation.