biostudies-literatureValente RFundação para a Ciência e a TecnologiaEuropean Social FundPortuguese fundsevaf246https://www.ebi.ac.uk/biostudies/studies/S-EPMC12862489biostudies-literatureUnknown18(2)Understanding how extant physiological landscapes arise from novel genetic interactions is key to elucidating phenotypic evolution. Sperm cells exemplify a striking case of functional compartmentalization shaped by molecular adjustments, notably regarding energy metabolism. Here, we examine the impact of gene duplication and loss on the evolution of sperm energetics in mammals. Our findings reveal that the acquisition of an exclusive mechanism controlling the sperm plasma membrane Na+ gradient, critical for glucose uptake, emerged in the ancestor of mammals through gene duplication, which originated the Na+/K+ ATPase transporting subunit alpha 4 transporter (Atp1a4). Furthermore, we demonstrate that testis-specific expression of Atp1a4 was acquired after the divergence from monotremes. NotGenome biology and evolutionParallel Erosion of a Testis-Specific Na+/K+ ATPase in Three Mammalian Lineages Sheds Light into the Evolution of Spermatozoa Energetics.PMC128624892023/08949/CEECINDLA/P/0101/2020UID/PRR/04423/2025PID2021-122507OB-I00UID/04423/2025MCIN1/AEI/10.13039/501100011033Castro LFCAlves FPinto BMachado AMValente RRuivo RArtilheiro NCordeiro JMPericuesta EGarcia-Parraga DGutierrez-Adan ASousa-Pinto IfalseParallel Erosion of a Testis-Specific Na+/K+ ATPase in Three Mammalian Lineages Sheds Light into the Evolution of Spermatozoa Energetics.Understanding how extant physiological landscapes arise from novel genetic interactions is key to elucidating phenotypic evolution. Sperm cells exemplify a striking case of functional compartmentalization shaped by molecular adjustments, notably regarding energy metabolism. Here, we examine the impact of gene duplication and loss on the evolution of sperm energetics in mammals. Our findings reveal that the acquisition of an exclusive mechanism controlling the sperm plasma membrane Na+ gradient, critical for glucose uptake, emerged in the ancestor of mammals through gene duplication, which originated the Na+/K+ ATPase transporting subunit alpha 4 transporter (Atp1a4). Furthermore, we demonstrate that testis-specific expression of Atp1a4 was acquired after the divergence from monotremes. Not2026-01-01T00:00:00Z2026 Jan2026-07-15T01:50:04.861Z2026-06-27T03:18:38.276ZS-EPMC128624894162671710.1093/gbe/evaf246