Abstract
<title>Abstract</title> <p> <bold>Background</bold> In tomato ( <italic>Solanum lycopersicum</italic> ), breeding for larger fruit has been accompanied by a decline in sugar content, and large fresh-market fruit remain difficult to raise to high soluble-solids content. Whether sugar and fruit weight are genetically separable is contested. <bold>Methods</bold> We define an Independence-Aware Locus Audit (IALA) and apply it to 118 soluble-sugar and 59 fruit-weight loci from nine tomato genome-wide association and QTL studies (seven independent germplasm panels), harmonized to the SL4.0 assembly. A sugar region was classified as positionally decoupling when no fruit-weight locus mapped within ±2 Mb; reproducibility was scored by the number of independent panels and non-random association was tested by permutation. <bold>Results</bold> The genome-wide decoupling rate was strongly panel-dependent (0.28 versus 0.74; pooled I² = 86%), reconciling the conflicting literature, yet sugar and fruit-weight loci co-localized more than expected by chance. At the locus level, positional separability was not equivalent to functional weight-independence: the most reproducible decoupling region (chromosome 5) dissolved into distinct sugar species and a re-tabulated, yield-penalized classical QTL, whereas a region the rule called antagonistic (chromosome 11) harbours a functionally validated weight-independent gene. Positional co-localization therefore misclassifies separability in both directions; cross-validation confirms the framework is robust to dropping any single study and predicts held-out co-localization above chance. <bold>Conclusions</bold> Only two reproducible loci— <italic>LIN5</italic> and <italic>SSC11.1</italic> / <italic>SlCDPK27</italic> —are functionally validated, weight-independent targets; every other call is a hypothesis requiring trait-resolved mapping. Treated this way, “large fruit cannot be sweet” becomes a tractable, locus-by-locus breeding question rather than a presumed physiological rule. </p>