A domestication gene links plant architecture and nitrogen metabolism to enhance yield in foxtail millet

Foxtail millet (Setaria italica) has lagged in yield compared with major cereals, largely due to suboptimal architecture. Here, we report a telomere-to-telomere (T2T) genome assembly of the dwarf, multi-tillering cultivar Dungu and identify SiSD1 (Semi Dwarf 1) via map-based cloning. This gene encodes GA20ox2, the rice SD1 ortholog involved in gibberellin biosynthesis. The loss-of-function sisd1 reduces bioactive gibberellins and remodels nitrogen metabolism, conferring semi-dwarfism, increased tillering, and higher yield. Critically, the semi-dominantly heterozygous SiSD1/sisd1 in F1 hybrids optimally balances stature, tillering, and nitrogen acquisition to drive yield heterosis. Genotype surveys confirm the prevalence of this allele in elite commercial hybrids, including the high-yield hybrid Zhangzagu series. Mechanistically, the SiSLR1-SiERF7/073 module precisely regulates SiSD1 transcription. D157E substitution in SiSD1 relative to its wild progenitor attenuates GA biosynthesis and has been favored during domestication. Collectively, SiSD1 functions as a pleiotropic integrator of development and nitrogen physiology, and deployment of its heterozygosity offers a targeted breeding strategy for crop improvement. Foxtail millet, like many crops, faces a trade-off between ideal architecture and nutrient use efficiency. Here, the authors clone a Green Revolution ortholog gene and show its semi-dominant heterozygous allele combination can balance growth and nitrogen use to enhance yield heterosis.