Allele-specific expression reveals complex regulatory divergence underlying fruit phenotypic differences between cultivated and wild tomato species

Abstract Background Tomato ( Solanum lycopersicum ) is one of the most important agricultural crops and serves as a model system for fleshy fruit biology. However, domestication bottlenecks have led to limited genetic diversity for further crop improvement. Wild relatives represent a rich reservoir of phenotypic diversity, yet the molecular basis underlying such phenotypic diversity remains largely unknown. Results As gene expression variation is a major driver of phenotypic diversity, we perform genome-wide allele-specific expression analyses in F 1 hybrids between cultivated tomato and three wild relatives spanning a range of evolutionary distances, across three fruit tissues and multiple developmental stages. Our analysis generates a multi-species map of cis - and trans -regulatory variation, revealing a predominant role of cis -regulatory effects in expression divergence across species, tissues, and stages. The majority of cis effects are tissue- and/or stage-specific, underscoring the importance of tissue context in regulatory variation. Regulatory mechanisms and inheritance patterns shift with evolutionary distance, with more distantly related species showing increased cis -regulatory contributions. Finally, we identify extensive regulatory divergence in biosynthetic pathways related to fruit nutritional value and flavor quality, including carotenoids, flavonoids, alkaloids, sugars, and volatiles. Conclusions This study presents a high-resolution map of regulatory variation underlying tomato fruit development and provides evolutionary insights into the regulation of fruit nutrition and flavor traits.