Comparative Multi-Omics Analysis Reveals Systems-Level Molecular Dysfunctions Underlying Salt Sensitivity in Solanum lycopersicum

Background Soil salinity threatens over 20% of global cultivated land and is projected to affect 50% of arable areas by 2050, posing critical challenges to food security. While Arabidopsis thaliana exhibits moderate salt tolerance through well-characterized mechanisms including the SOS signaling pathway, economically vital crops like Solanum lycopersicum (tomato) demonstrate extreme salt sensitivity despite possessing orthologs of key salt tolerance genes. Understanding the molecular determinants underlying this species-specific salt tolerance disparity is essential for developing rational crop improvement strategies. Results Through comprehensive multi-layered silico analysis of 14 curated salt tolerance genes, we revealed complex evolutionary patterns underlying salt sensitivity of tomato. Four critical genes (NHX2, WRKY8, MYB74, CHX17) were completely lost in tomato, while five others underwent expansion but with compromised functionality. Noticeably, key regulatory genes exhibited opposite transcriptional responses under salt stress. HAK5 showed robust induction in Arabidopsis (+3.42 LogFC) but repression in tomato (-0.36 LogFC), while SOS3 demonstrated strong activation in Arabidopsis (+2.26 LogFC) versus downregulation in tomato (-0.27 LogFC). Promoter analysis revealed 3 to 6 fold depletion of stress-responsive cis-elements in tomato genes, with WRKY motifs showing the greatest disparity. Structural modeling identified significant conformational divergence in critical proteins, including increased disorder in tomato SOS1 and loss of transmembrane domain in SOS2. Evolutionary analysis revealed positive selection in expanded gene families, indicating adaptive evolution that paradoxically correlates with reduced salt tolerance. Conclusions Tomato's salt sensitivity results from systems-level dysfunction involving coordinated gene loss, structural protein divergence, transcriptional network remodeling, and regulatory element depletion rather than simple absence of salt tolerance machinery. These findings necessitate a paradigm shift from gene complementation approaches toward comprehensive systems-level engineering strategies for enhancing crop salt tolerance, providing a mechanistic framework for developing salt-tolerant crops essential for future food security.