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How did George Beadle and Edward Tatum develop the one gene-one enzyme hypothesis?

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In the early 1940s, George Beadle and Edward Tatum developed the one gene–one enzyme hypothesis by studying metabolic pathways in the mold Neurospora crassa.12

Their experimental process involved:

  • Inducing Mutations: They exposed the mold to X-rays to create genetic mutations.12
  • Screening for Defects: They cultured the mutated mold in a minimal growth medium. Strains that failed to grow unless supplemented with specific amino acids or vitamins were identified as having metabolic defects.12
  • Genetic Verification: By crossing these mutants with normal strains, they proved the defects were inherited as recessive traits, confirming they were caused by genetic mutations.2
  • Linking Genes to Enzymes: They demonstrated that each mutation disrupted a specific chemical reaction, which corresponded to a missing or altered enzyme.12

This work established that genes control specific biochemical processes, earning them the 1958 Nobel Prize. While foundational, the hypothesis has since been refined, as we now know some enzymes are composed of multiple polypeptides encoded by different genes.12