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Red-fleshed watermelons (Citrullus lanatus) that accumulate lycopene in their flesh cells have been selected and domesticated from their pale-fleshed ancestors. However, the molecular basis of this trait remains poorly understood. Using map-based cloning and transgenic analysis, we identified a lycopene β-cyclase (ClLCY gene that controls the flesh color of watermelon. Downregulation of ClLCYB caused the flesh color to change from pale yellow to red, and ClLCYB overexpression in the red-fleshed line caused the flesh color to change to