A few years after he and James Watson had proposed the double helical structure for DNA, Francis Crick (with other collaborators) proposed that a less stable nucleic acid, RNA, served as a messenger RNA that provided a transient copy of the genetic material that could be translated into the protein product encoded by the gene. Such mRNAs were indeed found. These and other studies led Francis Crick to formulate this “central dogma” of molecular biology (Fig. 1.21).
This model states that DNA serves as the repository of genetic information. It can be replicated accurately and indefinitely. The genetic information is expressed by the DNA first serving as a template for the synthesis of (messenger) RNA; this occurs in a process called transcription. The mRNA then serves as a template, which is read by ribosomes and translatedinto protein. The protein products can be enzymes that catalyze the many metabolic transformations in the cell, or they can be structural proteins.
Figure 1.21.The central dogma of molecular biology.
Although there have been some additional steps added since its formulation, the central dogma has stood the test of time and myriad experiments. It provides a strong unifying theme to molecular genetics and information flow in cell biology and biochemistry.
Although in many cases a gene encodes one polypeptide, other genes encode a functional RNA. Some genes encode tRNAs and rRNAs needed for translation, others encode other structural and catalytic RNAs. Genes encode some product that is used in the cell, i.e. that when altered generates an identifiable phenotype. More generally, genes encode RNAs, some of which are functional as transcribed (or with minor alterations via processing) such as tRNAs and rRNAs, and others are messengers that are then translated into proteins. These proteins can provide structural, catalytic and regulatory roles in the cell.
Note the static role of DNA in this process. Implicit in this model is the idea that DNA does not provide an active cellular function, but rather it encodes macromolecules that are functional. However, the expression of virtually all genes is highly regulated. The sites on the DNA where this control is exerted are indeed functional entities, such as promoters and enhancers. In this case, the DNA is directly functional (cis‑regulatory sites), but the genes being regulated by these sites still encode some functional product (RNA or protein).
Studies of retroviruses lead Dulbecco to argue that the flow of information is not unidirectional, but in fact RNA can be converted into DNA (some viral RNA genomes are converted into DNA proviruses integrated into the genome). Subsequently Temin and Baltimore discovered the enzyme that can make a DNA copy of RNA, i.e. reverse transcriptase.