GNN - Genetics and Genomics Timeline

Francis H. C. Crick
Courtesy The Salk Institute

Once it became clear that genes are activated to make useful proteins, it became of the greatest interest to discover the molecular machinery involved. But evidence was confusing, and by the late 1950s the question of how exactly information from DNA was translated into proteins loomed as a roadblock for molecular biology.

The problem of the "missing messenger" was solved with a combination of experiment and collective insight about the role of ribonucleic acid (RNA). The close chemical kin to DNA—the principal difference is that uracil, rather than thymine, is one of the bases—RNA was known to play at least one role in protein synthesis. RNA-containing molecules, known as ribosomes, were found in the cytoplasm of cells, and protein synthesis could not proceed without them. But it remained unclear how ribosomal RNA received specific information from DNA.

François Jacob

In this regard, experiments with E. coli bacteria, conducted at the Institut Pasteur, became the focus of intense interest in 1959. The "PaJaMo" experiments—performed by Arthur Pardee, François Jacob, and Jacques Monod—built upon research into the system of bacterial enzyme production pioneered by Jacques Monod. They involved observations of carefully controlled gene transfer during conjugation—mating between "male" and "female" bacteria.

In previous experiments, Monod had learned how to genetically manipulate the compounds that control sugar metabolism in E. coli—collectively known as the B-galactosidase system. He had first bred mutated "female" bacteria in which this system ceased to function. When normal "male" bacteria then penetrated and inserted genes into such bacteria, however, the system was immediately—within minutes—restored to normal and the bacteria could digest sugar. How such information transfer could take place so quickly suggested the existence of a specific, relatively simple molecule that was complementary to DNA.

Jacques Monod
Courtesy the Archives, California Institute of Technology

Discussions among Monod, Jacob, Crick, and Brenner led to a solution. They recalled research from the early 1950s with bacteriophages—viral parasites that invade bacteria. Experiments had shown that soon after bacteriophages insert their DNA into bacterial cells, traces of RNA rapidly appear. In addition, the composition of such RNA closely resembled the DNA of the invading bacteriophage.

With this as context, the PaJaMo experiments suggested that another type of RNA was rapidly synthesized from DNA. Comparatively short-lived, its crucial presence had been initially overlooked. But in 1960, François Jacob and Jacques Monod named this hypothetical molecule "messenger RNA" (mRNA). Its presence was subsequently confirmed by experiment.

As it was finally understood, several types of RNA represent a basic division of labor in protein synthesis. Messenger RNA (mRNA) presents information contained in DNA sequences to the ribosomes, which are structured by ribosomal RNA (rRNA). Other molecules, known as transfer RNA (tRNA), attach to specific amino acids and conduct them to the ribosomes for protein synthesis.

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