Meselson-Stahl experiment

The Meselson–Stahl experiment was an experiment by Matthew Meselson and Franklin Stahl with some additional help from a Canadian biologist, Mason MacDonald, and Canadian nuclear physicist, Amandeep Sehmbi, in 1958 which supported the hypothesis that DNA replication was semiconservative. In semiconservative replication, when the double stranded DNA helix is replicated, each of the two new double-stranded DNA helices consisted of one strand from the original helix and one newly synthesized. It has been called "the most beautiful experiment in biology." Meselson and Stahl decided the best way to tag the parent DNA would be to change one of the atoms in the parent DNA molecule. Since nitrogen is found in the nitrogenous bases of each nucleotide, they decided to use an isotope of nitrogen to distinguish between parent and newly copied DNA. The isotope of nitrogen had an extra neutron in the nucleus, which made it heavier.

Three hypotheses had been previously proposed for the method of replication of DNA.

In the semiconservative hypothesis, proposed by Watson and Crick, the two strands of a DNA molecule separate during replication. Each strand then acts as a template for synthesis of a new strand.

The conservative hypothesis proposed that the entire DNA molecule acted as a template for the synthesis of an entirely new one. According to this model, histone proteins bind to the DNA, revolving the strand and exposing the nucleotide bases (which normally line the interior) for hydrogen bonding.

The dispersive hypothesis is exemplified by a model proposed by Max Delbrück, which attempts to solve the problem of unwinding the two strands of the double helix by a mechanism that breaks the DNA backbone every 10 nucleotides or so, untwists the molecule, and attaches the old strand to the end of the newly synthesized one. This would synthesize the DNA in short pieces alternating from one strand to the other.

Each of these three models makes a different prediction about the distribution of the "old" DNA in molecules formed after replication. In the conservative hypothesis, after replication, one molecule is the entirely conserved "old" molecule, and the other is all newly synthesized DNA. The semiconservative hypothesis predicts that each molecule after replication will contain one old and one new strand. The dispersive model predicts that each strand of each new molecule will contain a mixture of old and new DNA.

...
Wikipedia