The major compositional difference between DNA and RNA lies in their sugar and nitrogenous bases. DNA contains deoxyribose sugar, while RNA contains ribose sugar. This difference leads to variations in stability and function; DNA is usually double-stranded and serves primarily as the genetic blueprint for organisms, whereas RNA is typically single-stranded and plays roles in protein synthesis and gene expression. Additionally, RNA includes uracil as one of its nitrogenous bases instead of thymine, which is found in DNA. These distinctions are crucial for their respective biological roles.