Repairing a deleterious domestication variant in a floral regulator gene of tomato by base editing

Crop genomes accumulated deleterious mutations, a symptom known as the cost of domestication. Precision genome editing has been proposed to eliminate such potentially harmful mutations, however, experimental demonstration is lacking. Here, we identified a deleterious mutation in the tomato transcription factor SUPPRESSOR OF SP2 (SSP2), which became prevalent in the domesticated germplasm and diminished DNA-binding to genome-wide targets. We found that SSP2 acts partially redundant with its paralog SSP to regulate shoot and inflorescence architecture. However, redundancy was compromised during tomato domestication and completely lost in the closely-related species Physalis grisea, in which a single ortholog regulates shoot branching. We applied base editing to directly repair the deleterious mutation in cultivated tomato and obtained plants with compact growth that provide an early fruit yield. Our work shows how deleterious variants sensitized modern genotypes for phenotypic tuning and illustrates how repairing deleterious mutations with genome editing may allow predictable crop improvement.