Genomic evolution of ADH/RDH/ALDH genes and ALDH1A2 in grouper development

Retinoic acid (RA) signaling functions as a critical inducer of meiotic initiation and gonadal differentiation in teleosts. While the ADH (alcohol dehydrogenase), RDH (retinol dehydrogenase), and ALDH (aldehyde dehydrogenase) gene families responsible for RA biosynthesis have undergone significant expansion in fish, their evolutionary dynamics and regulatory complexity remain largely underexplored. Here, we conducted a systematic comparative genomic analysis across 21 representative invertebrate and vertebrate species. Our results reveal that while the ADH and ALDH superfamilies have remained relatively stable under strict purifying selection, the RDH family displays marked lineage-specific expansion. Focusing on the protogynous hermaphrodite Epinephelus coioides , we characterized 50 gene family members and determined that the teleost-specific whole-genome duplication (Ts-WGD) served as the primary driver for the diversification of specific clades, alongside the retention of ancient vertebrate syntenic blocks. Spatiotemporal transcriptomic profiling identified aldh1a2 as a pivotal regulator, exhibiting peak expression preceding the onset of both ovarian and testicular differentiation. Long-term in vivo inhibition of ALDH1A2 using DEAB resulted in severe somatic growth retardation and gonadal atrophy. Mechanistic investigation revealed that somatic growth arrest was linked to the transcriptional suppression of lipid metabolism regulators, such as srebf1 and fabp2 . In the gonad, RA blockade precipitated a functional discordance in steroid signaling: the suppression of the catabolic enzyme hsd17b2 caused an aberrant accumulation of circulating sex steroids (E 2 and MT). However, the synchronous downregulation of key receptors, including specific esr and ar subtypes, rendered the tissue unresponsive to hormonal stimulation, ultimately leading to germ cell depletion. These findings suggest that the integrity of the retinoid metabolic network is essential for supporting somatic growth and maintaining the precise coupling between steroid availability and local receptor sensitivity, thereby serving as a fundamental mechanism for gonadal developmental homeostasis in teleosts.