The Meselson–Stahl experiment

Membranes, Proteins, DNA and Gene Expression · DNA, the genetic code and gene expression · note 3 of 7

The Meselson–Stahl experimentSpec 2.10

In short

Meselson and Stahl grew bacteria in heavy nitrogen (¹⁵N), then transferred them to light nitrogen (¹⁴N) and separated their DNA by density in a centrifuge. After one generation all the DNA was of intermediate density, and after two generations half was intermediate and half light, which supports semi-conservative replication.

Three models were proposed for how DNA could be copied. In the conservative model the original molecule stays intact and a completely new molecule is made. In the semi-conservative model each new molecule has one old and one new strand. In the dispersive model, each strand is a mixture of old and new DNA.

The experiment

  1. Bacteria (E. coli) were grown for many generations in a medium with heavy nitrogen, ¹⁵N, so all their DNA contained ¹⁵N (heavy DNA).
  2. The bacteria were transferred to a medium containing only normal, lighter nitrogen, ¹⁴N, and allowed to divide. New DNA could only be made using ¹⁴N.
  3. Samples were taken after each generation. The DNA was extracted and spun in a centrifuge in a caesium chloride solution, which separates DNA by density into bands.
Results and what each model predicted
SampleResult observedConservative modelSemi-conservative modelDispersive model
Start (all ¹⁵N)One band, heavyOne heavy bandOne heavy bandOne heavy band
After 1 generationOne band, intermediate densityTwo bands: heavy and light (not matching)One intermediate band (matches)One intermediate band (matches)
After 2 generationsTwo bands: intermediate and lightHeavy and light bands (not matching)Intermediate and light bands (matches)One band, lighter than intermediate (not matching)

After one generation, a single band of intermediate density rules out the conservative model, which would give separate heavy and light bands. After two generations, the presence of both an intermediate and a light band rules out the dispersive model, which would give a single band of lower density. Only the semi-conservative model fits both results. The new data therefore supported the accepted theory and refuted the competing theories.

Exam tip:

In a data question, state what the band positions mean in terms of nitrogen (heavy = both strands ¹⁵N, intermediate = one ¹⁵N strand and one ¹⁴N strand, light = both strands ¹⁴N), then compare with each model's prediction.

Centrifuge tubes showing DNA bands for the parent generation (one heavy band), generation 1 (one intermediate band), generation 2 (intermediate and light bands) and generation 3 (thin intermediate and thick light band), with DNA strands drawn beneath each tube using 15N and 14N. (opens full size in a new tab)
The Meselson–Stahl results support semi-conservative replication.

Written and checked against the Edexcel International A Level Biology (YBI11) specification · Updated October 2026

Frequently asked questions

What is the difference between DNA and RNA?

DNA is a double helix made of two polynucleotide strands, with deoxyribose and the bases A, T, C and G. RNA is a single polynucleotide strand with ribose, and uracil instead of thymine. DNA stores genetic information in the nucleus; mRNA, tRNA and rRNA are involved in protein synthesis.

What does semi-conservative replication mean?

In semi-conservative replication each new DNA molecule contains one original strand and one new strand. The helix unwinds, each strand acts as a template, and DNA polymerase joins complementary nucleotides to it. The Meselson and Stahl experiment, using heavy and light nitrogen, gave evidence for it.

What is the genetic code and why is it degenerate?

The genetic code is the set of rules by which base triplets code for amino acids. It is a non-overlapping triplet code. It is degenerate because there are 64 possible triplets but only 20 amino acids, so most amino acids are coded for by more than one triplet.

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