The Meselson - Stahl Experiment

"the most beautiful experiment in biology"

DNA Replication is Semiconservative

• separated from each other but
• remained intact as each served as the template for the synthesis of
• a complementary strand.

This mode of replication is described as semiconservative: one-half of each new molecule of DNA is old; one-half new.

While Watson and Crick had suggested that this was the way the DNA would turn out to be replicated, proof of the model came from the experiments of M. S. Meselson and F. W. Stahl.

They grew E. coli is a medium using ammonium ions (NH₄⁺) as the source of nitrogen for DNA (as well as protein) synthesis. ¹⁴N is the common isotope of nitrogen, but they could also use ammonium ions that were enriched for a rare heavy isotope of nitrogen, ¹⁵N.

After growing E. coli for several generations in a medium containing ¹⁵NH₄⁺, they found that the DNA of the cells was heavier than normal because of the ¹⁵N atoms in it.

The difference could be detected by extracting DNA from the E. coli cells and spinning it in an ultracentrifuge. The density of the DNA determines where it accumulates in the tube.

The DNA in this new generation of cells was exactly intermediate in density between that of the previous generation and the normal.

This, in itself, is not surprising. It tells us no more than that half the nitrogen atoms in the new DNA are ¹⁴N and half are ¹⁵N. It tells us nothing about their arrangement in the molecules.

• half the DNA was normal and
• half was intermediate.

As this interpretative figure indicates, their results show that DNA molecules are not degraded and reformed from free nucleotides between cell divisions, but instead, each original strand remains intact as it builds a complementary strand from the nucleotides available to it.

This is called semiconservative replication because each daughter DNA molecule is one-half "old" and one-half "new".

Immortal strands. Note that the "old" strand (the red one in the top half of the figure) is immortal because — barring mutations or genetic recombination — it will continue to serve as an unchanging template down through the generations.

E. coli is a bacterium, but semiconservative replication of DNA also occurs in eukaryotes. And because each DNA molecule in a eukaryote is incorporated in one chromosome, the replication of entire chromosomes is semiconservative as well. This also means that the eukaryotic chromosome contains one "immortal strand" of DNA.