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Meselson and Stahl conducted an experiment using nitrogen isotopes to prove semiconservative DNA replication.
Ref: NCERT Class 12 Biology Chapter 5: Molecular Basis of Inheritance DNA Replication - Semiconservative and Machinery
Meselson and Stahl in 1958 grew Escherichia coli in 15N labeled ammonium chloride, then shifted to light 14N medium, extracting DNA at generations and separating by CsCl density gradient ultracentrifugation. Fully heavy DNA banded at high density, after one generation all DNA appeared at hybrid density demonstrating one old heavy strand paired with one new light strand, eliminating conservative model that predicted separate heavy and light bands. Second generation produced hybrid and light bands equally, ruling out dispersive model that would yield intermediate density. Experiment elegantly proved semi-conservative replication of double helix.
Ref: Meselson M, Stahl FW, PNAS 1958: Meselson-Stahl Experiment Proved DNA Replication is Semi-Conservative
