MeselsonStahlin

The Meselson-Stahl experiment, conducted by Matthew Meselson and Franklin Stahl in 1958, provided crucial evidence for the semi-conservative replication of DNA. At the time, there were three proposed models for DNA replication: conservative, semi-conservative, and dispersive. The conservative model suggested that the original DNA molecule remained intact and a new, identical molecule was synthesized. The dispersive model proposed that both new and old DNA were mixed together in the daughter molecules. The semi-conservative model, which was eventually supported by the experiment, stated that each new DNA molecule would consist of one original strand and one newly synthesized strand.

Meselson and Stahl used a clever experimental design involving isotopes of nitrogen. They grew bacteria in a medium containing heavy nitrogen (¹⁵N) for many generations, ensuring that all their DNA incorporated this heavy isotope. Subsequently, they transferred these bacteria to a medium containing normal nitrogen (¹⁴N) and allowed them to divide once. They then isolated the DNA and analyzed its density using cesium chloride density gradient centrifugation. The DNA from the first generation of bacteria grown in the ¹⁴N medium showed a density intermediate between heavy and normal nitrogen, indicating that each DNA molecule contained one heavy strand and one light strand, consistent with semi-conservative replication.

After allowing the bacteria to divide a second time in the ¹⁴N medium, the DNA analysis revealed two distinct bands: one with intermediate density and another with normal density. This further supported the semi-conservative model, as half of the DNA molecules still contained one heavy strand and one light strand (intermediate density), while the other half consisted of entirely new strands made with normal nitrogen (normal density). The Meselson-Stahl experiment is considered a landmark in molecular biology, definitively settling the question of DNA replication mechanism and solidifying our understanding of heredity.