Meselson-Stahl Experiment: Videos & Practice Problems

The Meselson-Stahl experiment, conducted in 1958 by Matthew Meselson and Franklin Stahl, demonstrated that DNA replication follows the semiconservative model. This means that each new DNA molecule consists of one parental strand and one newly synthesized strand. They used nitrogen isotopes, N₁₅ for old strands and N₁₄ for new strands, to label the DNA. This experiment is crucial because it confirmed the mechanism of DNA replication, which is fundamental for understanding genetic inheritance and molecular biology principles.

Meselson and Stahl used nitrogen isotopes to distinguish between old and new DNA strands. They grew E. coli in a medium containing N₁₅ (a heavy isotope of nitrogen) so that the DNA incorporated this isotope. They then switched the bacteria to a medium containing N₁₄ (a lighter isotope). During DNA replication, the old strands containing N₁₅ served as templates for new strands incorporating N₁₄. This allowed them to track the distribution of old and new DNA strands through density gradient centrifugation, confirming the semiconservative model of DNA replication.

Before the Meselson-Stahl experiment, three models of DNA replication were considered: the conservative model, the semiconservative model, and the dispersive model. The conservative model proposed that the original DNA molecule remains intact and a completely new molecule is synthesized. The semiconservative model, which was confirmed by Meselson and Stahl, proposed that each new DNA molecule consists of one old (parental) strand and one newly synthesized strand. The dispersive model suggested that the original DNA molecule is broken into pieces and dispersed throughout the new DNA molecules. Meselson and Stahl's experiment disproved the conservative and dispersive models.

The key findings of the Meselson-Stahl experiment were that DNA replication follows the semiconservative model. This means that each new DNA molecule consists of one parental strand and one newly synthesized strand. By using nitrogen isotopes (N₁₅ for old strands and N₁₄ for new strands) and density gradient centrifugation, they demonstrated that after one round of replication, DNA molecules consisted of hybrid strands (one old and one new). After subsequent rounds, the DNA showed a mix of hybrid and fully new DNA molecules, confirming the semiconservative replication model.

The Meselson-Stahl experiment disproved the conservative and dispersive models of DNA replication through the use of nitrogen isotopes and density gradient centrifugation. The conservative model predicted that after replication, there would be one molecule with entirely old DNA and one with entirely new DNA, which was not observed. The dispersive model predicted that DNA would be a mix of old and new segments within each strand, resulting in intermediate densities after each replication cycle. However, the experiment showed distinct bands corresponding to hybrid DNA (one old and one new strand) and fully new DNA, consistent with the semiconservative model.