The Central Dogma Of Molecular Biology

In 1953 a young American geneticist named James Watson (1928- ) and his British colleague Francis Crick (1916-2004) had a brilliant insight into the building plan of the DNA molecule that accomplished several things:

• It demonstrated that DNA almost certainly contained the hereditary material of cells and organisms;

• It revealed how cells could copy DNA to pass it along to their offspring; and

• It showed how the molecule might change through mutations, which make evolution possible.

The new structure proposed by Watson and Crick caused a sensation in the scientific community because it made sense of some physical measurements that their British colleague Rosalind Franklin (1920-58) had made of DNA. It also explained studies that measured amounts of the four DNA building blocks, or nucleotides, in different species. The story is told in detail in chapter 2; it is mentioned here because it launched a new era in biology that shifted the focus toward the interactions between different types of molecules in cells.

Researchers had known of the existence of genes for half a century; the chemical substance they were made of, however, remained a mystery. The discovery of Watson and Crick immediately answered that question while raising many new ones. DNA not only was a library of information passed down from parent to child, or plant to seed, but also played an active role in the daily life of the cell. This was demonstrated in the 1940s by the American geneticists George Beadle (1903-89) and Edward Tatum (1909-75). Their experiments showed that a mutation in a single gene caused a type of mold to lose a single enzyme (a type of protein). This strongly suggested that whatever each gene was made of, it was responsible for the production of one protein. DNA and proteins were completely different kinds of molecules. How was the information in genes translated into another form? Beadle had already said that the issue would probably turn out to be very complex. In an article in a 1945 edition of Physiological Reviews, he stated that his work did not mean that genes directly make proteins. "In the synthesis of a single protein molecule," he wrote, "probably at least several hundred different genes contribute. But the final molecule corresponds to only one of them and this is the gene we visualize as being in primary control."

Crick provided a road map toward finding the answer in 1958 when he stated what is called the "central dogma" of molecular biology: "DNA makes RNA makes proteins." In other words, genetic information was transcribed into an intermediate molecule called RNA, which was then used to make a protein. No one knew how that happened; Crick's hypothesis was a challenge to the entire scientific community to figure it out. Within about 15 years researchers around the world had worked out the main steps in the process. Predictably, the answers raised

Central Dogma

Cell membrane

Cell membrane

1. Genetic information is encoded in DNA.

2. A gene transcribed into a messenger RNA molecule.

3. Messenger RNA is translated into a protein.

G Infobase Publishing

Francis Crick's statement "DNA makes RNA makes proteins" established a road map for research in molecular biology between the late 1950s and 1970s. Working out the details of the pathway between an organism's genome and the molecules it produces is still the major focus of many laboratories throughout the world.

new questions that in one way or another are the subject of most of the work going on in today's biological laboratories.

Crick's central dogma had several implications. The theory that "DNA makes

RNA makes proteins" meant that information was transmitted in a one-way direction. Each RNA was produced from the information in a gene, but the RNA could not send information back and change the gene. Likewise, an RNA could be used to make a protein, but a protein could not influence the content of the RNA. As chapter 2 will show, researchers have since discovered interesting exceptions to this rule; for example, RNAs can indeed sometimes rewrite the information of genes. Beadle and Tatum's principle of "one gene makes one enzyme" has also proven to be too simple. It is true that a gene cannot encode two completely different proteins, but one RNA can be used to produce very different forms of one protein, the way that the same ingredients and the same recipe can lead to different dishes if a cook leaves out steps, adds new ones, or changes their order. At every step in the transformation of genetic information into proteins, cells have evolved control mechanisms that enable them to step in and refine or block the process. The history of molecular biology since 1950 has been a process of working out the details and the exceptions to the central dogma, so it is one of the main themes of this volume.

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