Grain weight has increased during domestication of cereals. Together with grain number it determines yield, but the two are often negatively correlated. Understanding the genetic architecture of grain weight and its relationship with grain number is critical to enhance crop yield. Sorghum is an important food, feed, and biofuel crop well-known for its adaptation to drought and heat. This study aimed to dissect the genetic basis of thousand grain weight (TGW) in a BC₁F₅ population between a domesticated sorghum accession and its wild progenitor, Sorghum bicolor subsp. verticilliflorum, and investigate its relationship with grain number. Thousand grain weight, grain number, and yield were measured in field trials in two successive years. A strong negative correlation between TGW and grain number was observed in both trials. In total, 17 TGW quantitative trait loci (QTL) were identified, with 11 of them exhibiting an opposing effect on grain number, implying the correlation between TGW and grain number is due to pleiotropy. Nine grain size candidate genes were identified within 6 TGW QTL, and of these 5 showed signatures of selection during sorghum domestication. Read More Unique Grains Weight Loci Revealed inside the a mix ranging from Grown and Nuts Sorghum