Semiconservative replication describes the mechanism by which DNA is replicated in all known cells. This mechanism of replication was one of three models originally proposed  for DNA replication:
- Semiconservative replication would produce two copies that each contained one of the original strands and one new strand.
- Conservative replication would leave the two original template DNA strands together in a double helix and would produce a copy composed of two new strands containing all of the new DNA base pairs.
- Dispersive replication would produce two copies of the DNA, both containing distinct regions of DNA composed of either both original strands or both new strands.
The deciphering of the structure of DNA by Watson and Crick in 1953 suggested that each strand of the double helix would serve as a template for synthesis of a new strand. However, there was no way of knowing how the newly synthesized strands might combine with the template strands to form two double helical DNA molecules. The semiconservative model seemed most reasonable since it would allow each daughter strand to remain associated with its template strand. The semiconservative model was confirmed by the Meselson-Stahl experiment and other even more revealing experiments that allowed for autoradiographic visualization of the distribution of old and new strands within replicated chromosomes.
Testing the semi-conservative theory 
Biophysical evidence 
The semi-conservative theory can be confirmed by making use of the fact that DNA is made up of nitrogen bases. Nitrogen has an isotope N15 (N14 is the most common isotope) called heavy nitrogen. The experiment that confirms the predictions of the semi-conservative theory makes use of this isotope and runs as follows:
- Bacterial (E. coli) DNA is grown in a media containing heavy nitrogen (N15) through many cell divisions. During each round of DNA synthesis, N15 is incorporated, so that after several rounds of replication most bacterial DNA is composed of N15.
- N15-containing DNA is then placed in a media with the presence of N14 and left to replicate twice, with some DNA removed after the first division as well as the second division. Newly incorporated bases will contain N14 while the original bases will contain N15.
- The DNA is placed in test tubes containing caesium chloride (heavy compound) and centrifuged at 40,000 revolutions per minute.
- The caesium chloride molecules sink to the bottom of the test tubes creating a density gradient. The DNA molecules will position at their corresponding level of density (taking into account that N15 is more dense than N14)
- These test tubes are observed under ultraviolet rays. DNA appears as a fine layer in the test tubes at different heights according to their density.
According to the semi-conservative theory, after one round of DNA replication, we should obtain 2 hybrid (1/2 N14, 1/2 N15) molecules from each original strand of DNA. This would appear as a single line in the test tube. This result would be the same for the dispersive theory. On the other hand, according to the conservative theory, we should obtain one original DNA strand and a completely new one i.e. two fine lines in the test tube placed separately one from the other. Experimental evidence confirmed that only one line appeared after one round of replication, so given this information either the semi-conservative or the dispersive theories could be truthful. In order to conclude which of the two is the correct mechanism, DNA had to be left to replicate a second time, still in a media containing N14.
In the dispersive theory, after 2 divisions we should obtain a single line, but further up in the test tube relative to the 1/2 14N, 1/2 15N molecule observed after 1 cell division, as the DNA molecules become less dense as N14 becomes more abundantly incorporated. According to the semi-conservative theory, 2 hybrid molecules and 2 fully N14 molecules should be produced, so two fine lines at different heights in the test tubes should be observed. Experimental evidence confirmed that two lines were observed, therefore offering compelling evidence for the semi-conservative theory.
Genetic evidence 
An independent 'genetic' evidence for the semi-conservative theory was provided more recently by high throughput genomic sequencing of individual mutagenized bacteria.  E. coli were treated with Ethyl methanesulfonate (EMS), known to induce G:C → A:T transitions due to generation of abnormal base O-6-ethylguanine, which is further misrecognized during DNA replication and paired with T instead of C. The sequenced DNA from individual colonies of EMS-mutagenized bacteria exhibited long stretches of solely G → A or C → T transitions, which in some cases were spanning entire bacterial genome. The elementary of this observation is based on semi-conservative mechanism: one should expect the segregation between daughter strands into different cells after replication, which leads to each descendant cell having exclusively G → A or C → T conversions.
See also 
- Anthony J. F. Griffiths et al. (1999). "8. The Structure and Replication of DNA". An Introduction to genetic analysis. San Francisco: W.H. Freeman. ISBN 0-7167-3520-2.
- Meselson, M.; Stahl, F.W. (1958). "The Replication of DNA in Escherichia coli". PNAS 44: 671–82. doi:10.1073/pnas.44.7.671. PMC 528642. PMID 16590258.
- Parkhomchuk, D., Amstislavskiy, V., Soldatov, A. and Ogryzko V. (2009) "Use of high throughput sequencing to observe genome dynamics at a single cell level". PNAS 106: 20830-20835