A muscle-centered hierarchical breakdown underlies flight loss during silkworm domestication

Recurrent loss of complex traits such as insect flight offers insights into evolutionary regression, as seen in <i>Bombyx mori</i> domestication from its flight-capable ancestor <i>B. mandarina</i>. By integrating single-cell and spatial transcriptomics of developing flight organs in both <i>Bombyx</i> species, we reveal that flight loss occurs through a coordinated breakdown centered on flight muscle cells. This stems from disintegration of a multi-tiered genetic module with three interconnected components: failures in mitochondrial energy production (e.g., <i>COX3/ND1</i>), wing vein patterning (involving <i>Dally/CtBP</i>), and flight muscle specification (controlled by <i>Yki</i>). Knocking down key components in <i>B. mandarina</i> induced flightlessness, and perturbing the Hippo effector Yki in <i>B. mori</i> exacerbated wing defects, together highlighting the pathway's dosage-sensitive nature. Notably, this muscle-centric module is conserved in the migratory pest <i>Helicoverpa armigera</i>, where its disruption similarly impaired flight. Our work establishes trait degeneration as a muscle-centered collapse and identifies a conserved target for precision pest control.