Early biochemical genetics sought link between genes and metabolic enzymes. Beadle and Tatum irradiated Neurospora crassa, generating auxotrophic mutants unable to synthesize specific amino acids or vitamins on minimal medium but rescued by supplementation. Analyzing single mutations causing loss of single enzymatic activity, they proposed one gene directs production of one enzyme, later refined to one polypeptide. Conducted in 1941, this work using haploid fungus provided first molecular definition of gene function, preceding DNA structure discovery, and earned Nobel Prize for establishing biochemical basis of heredity.
Ref:
Beadle GW, Tatum EL, PNAS 1941, Genetic Control of Biochemical Reactions in Neurospora, One Gene-One Enzyme