What is the Meselson-Stahl experiment?

Introduction

Often called “the most beautiful experiment in biology”, the Meselson-Stahl Experiment was conducted by Matthew Meselson and Franklin Stahl in 1958.

During that time, there were three models of DNA replication being argued by scientists. The Meselson-Stahl experiment conclusively showed which of those was true. Let’s talk briefly about the models.

DNA replication models

As mentioned earlier, there were three models of DNA replication floating around in the 1950s.

Conservative

The DNA replication process results in two molecules, from which one has both the original DNA strands and the other has the two new strands.

Semi-conservative

Each of the parent strands of DNA unwinds from the other and serves as the template for replication for a new strand. The result is the creation of two DNA molecules, in which one is the original, and the other is a replication.

Dispersive

The two resulting DNA molecules are mixtures of the original two strands. So the resulting strands contain patches of the parent strands.

The experiment

Meselson and Stahl used the E. Coli bacteria to conduct their experiment. First, they began to grow the bacteria in $^{15}$N, which is the heavier isotope of Nitrogen. When the bacteria became saturated with the heavier isotope, they moved them to $^{14}$N, the lighter isotope.

What they found was that all of the newly synthesized DNA would contain $^{14}$N only. This allowed them to identify the most accurate of the proposed models based on the model’s accuracy of prediction.

Observations

The conservative model had said that the DNA would be half $^{15}$N and half $^{14}$N in the first generation following replication. This meant that half of the DNA should have been heavier than the other half. However, when Meselson and Stahl attempted to separate the DNA by weight, they found that all the molecules had the same density. Thus, the conservative model was rejected.

In the second generation following replication, according to the dispersive model, any replicated strand should have contained about 25% $^{15}$N and 75% $^{14}$N. However, when they tested this using a centrifuge, they found that this was not the case. Thus, Meselson and Stahl also eliminated the dispersive model.

Results

Meselson and Stahl observed that the DNA had two distinct densities after the two replications, as predicted by the semiconservative model. However, to prove that this was true, they made observations after another generation of replicas had been made.

According to the semiconservative model, after three generations, approximately 25% of the modules would contain an $^{15}$N strand, and the rest would be $^{14}$N strands. Meselson and Stahl found this to be true at the end of their experiment, and therefore they concluded that the semiconservative model of DNA replication was correct.