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Modern Genetic Analysis Chapter 4. The Inheritance of Genes DNA Replication
Genetics In Process 4-1: Meselson and Stahl show that DNA replicates semiconservatively

In their 1953 paper first describing the structure of DNA, Watson and Crick ended with the brief, cryptic comment "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." To geneticists at the time, the meaning of this statement must have been clear: the two halves of the double helix must separate, and because of the specificity of base pairing, they both act as templates for the polymerization of new strands, thus forming two identical daughter double helices. This type of replication became known as semiconservative. A beautiful idea, but many beautiful ideas have been knocked down by ugly facts, so it was necessary to test the proposal. The first critical test was performed by Matthew Meselson and Frank Stahl.

Meselson and Stahl later wrote

We met each other as graduate students at Woods Hole in 1954, the second summer after the Watson-Crick model had been announced. Our first conversations concerned the solutions to certain integrals describing cross-reactivation of UV-induced phages, which one of us was then studying. Later we got to talking about ways to test the prediction of semiconservative duplication of DNA. Perhaps the more intriguing ideas have been forgotten, but we remember talking about the possible use of density as a label for parental DNA molecules.

The idea was to allow parental molecules containing components of one density to replicate in medium containing components of different density; if DNA replicated semiconservatively, the daughter molecules should be of intermediate density. Initial attempts to use this approach on phage using the heavy hydrogen isotope deuterium and the thymine analog 5-bromouracil (5BU) failed, but

Finally we abandoned phage and 5BU and turned to bacteria and the heavy isotope of nitrogen (15N). The second and third experiments along these lines worked beautifully; so we renumbered them 1 and 2 and began to write the paper.

The paper was published in 1958.

Different densities of DNA can be visualized by the positions DNA assumes in a density gradient of cesium chloride formed in an ultracentrifuge. (The high gravitational forces generated in the high-speed ultracentrifuge are needed to make the density gradient.) Cells initially grown in 15N showed DNA of high density. After growing these cells in 14N for one generation, the researchers found that the DNA was of intermediate density, and after two generations both intermediateand low-density DNA was observed, precisely as predicted by the Watson-Crick model.

© 1999 by W. H. Freeman and Company. All rights reserved.