Step 1: Understanding the Concept:
George Beadle and Edward Tatum (1941) proposed the 'One Gene-One Enzyme' hypothesis in Neurospora crassa.
Step 2: Detailed Explanation:
The hypothesis was subsequently modified to 'One Gene-One Polypeptide' and 'One Gene-One Transcript' due to four major molecular realities:
1. Heteromultimeric proteins (A): Many enzymes consist of multiple distinct polypeptide subunits encoded by separate genes (e.g., hemoglobin $\alpha_2\beta_2$, RNA polymerase core).
2. Non-enzymatic proteins (B): Structural proteins, antibodies, and peptide hormones are encoded by genes but are not enzymes.
3. Non-coding functional RNA genes (C): Genes transcribing rRNA, tRNA, snRNA, and microRNAs do not code for proteins or enzymes.
4. Alternative pre-mRNA splicing (D): A single eukaryotic gene locus can produce multiple distinct polypeptide isoforms via alternative exon splicing.
(Statement E was the experimental proof supporting the original hypothesis, not an exception).
Step 3: Final Answer:
Hence, statements A, B, C, and D only explain why the hypothesis is not universal.