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 Bombyx mori domestication from its flight-capable ancestor B. mandarina. By integrating single-cell and spatial transcriptomics of developing flight organs in both Bombyx 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., COX3/ND1), wing vein patterning (involving Dally/CtBP), and flight muscle specification (controlled by Yki). Knocking down key components in B. mandarina induced flightlessness, and perturbing the Hippo effector Yki in B. mori exacerbated wing defects, together highlighting the pathway's dosage-sensitive nature. Notably, this muscle-centric module is conserved in the migratory pest Helicoverpa armigera, 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.