When Watson and Crick solved the three-dimensional structure of DNA in 1953 (see Figure 8.12), several important genetic implications were immediately apparent. The complementary nature of the two nucleotide strands in a DNA molecule suggested that, during replication, each strand can serve as a template for the synthesis of a new strand. The specificity of base pairing (adenine with thymine; guanine with cytosine) implied that only one sequence of bases can be specified by each template, and so the two DNA molecules built on the pair of templates will be identical with the original. This process is called semiconservative replication because each of the original nucleotide strands remains intact (conserved), despite no longer being combined in the same molecule; the original DNA molecule is half (semi) conserved during replication.

Initially, three models were proposed for DNA replication. In conservative replication (Figure 9.1a), the entire double-stranded DNA molecule serves as a template for a whole new molecule of DNA, and the original DNA molecule is fully conserved during replication. In dispersive replication (­Figure 9.1b), both nucleotide strands break down (disperse) into fragments, which serve as templates for the synthesis of new DNA fragments, and then somehow reassemble into two complete DNA molecules. In this model, each resulting DNA molecule contains interspersed fragments of old and new DNA; none of the original molecule is conserved. Semiconservative replication (Figure 9.1c) is intermediate between these two models; the two nucleotide strands unwind, and each serves as a template for a new DNA molecule.

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These three models allow different predictions to be made about the distribution of original DNA and newly synthesized DNA after replication. With conservative replication, after one round of replication, 50% of the molecules would consist entirely of the original DNA and 50% would consist entirely of new DNA. After a second round of replication, 25% of the molecules would consist entirely of the original DNA and 75% would consist entirely of new DNA. With each additional round of replication, the proportion of molecules with new DNA would increase, although the number of molecules with the original DNA would remain constant. Dispersive replication would always produce hybrid molecules, containing some original and some new DNA, but the proportion of new DNA within the molecules would increase with each replication event. In contrast, with semiconservative replication, one round of replication would produce two hybrid molecules, each consisting of half original DNA and half new DNA. After a second round of replication, half the molecules would be hybrid, and the other half would consist of new DNA only. Additional rounds of replication would produce more and more molecules consisting entirely of new DNA, and a few hybrid molecules would persist.