The Central Dogma: DNA -> RNA -> Protein

DNA - Our Molecular Blueprint

The true ancestry of viruses is a mystery, and perhaps always will be, for viruses have left no fossil record behind them. They are so small that it is unlikely that any record of them has survived for very long, and they have only been known to science for about a hundred years - scarcely long enough to learn very much about their evolution.

Martinus Beijerinck, the scientist credited with the isolation of the first virus.

Some scientists believe that viruses evolved out of cells, gradually losing so much of their genetic information that they became dependent on other cells for their reproduction, or alternatively that they arose from bits of genetic material within the cell that acquired a life of their own. Other scientists believe that viruses originated and evolved along with the most primitive forms of life, the simple molecules that gained self-replicating abilities. Some of these took the form of cells - others evolved into the viruses which parasitized those same cells.

There are a number of complex molecular life forms that blur the boundaries cells and viruses. There are pieces of self-replicating genetic material found in bacteria, called episomes, which evolve independently of their hosts, and can even move from host to another - but carry genetic information that is beneficial or even essential to their host. Many bacteria would be unable to reproduce at all without them. Episomes are in many ways quite similar to viruses - except for the fact that they only reproduce themselves when their hosts do, whereas viruses reproduce themselves hundreds of times, causing disease.

Viroids and virusoids are the smallest and simplest form of all recognized viruses and self-replicating molecules. Viroids are composed of nothing more than a single, circular strand of genetic material, and cause disease in plant cells. Replicating in the nuclei of plant cells, they often cause striking diseases in their host plants. Lacking even a protective shell of protein, viroids do not even spread easily from one cell or plant to another. Virusoids, like viroids, are small, circular molecules of genetic material. Virusoids "infect" other viruses, using the replication processes of the host virus to replicate themselves instead.

The construction and operation of such a factory, particularly a factory that can replicate itself, is vastly beyond our abilities. Yet, a living cell has all of the properties of our metaphorical factory, and many others as well. We are surrounded by, and composed of, cells of astounding beauty and complexity.

An overarching question in biology relates to how our living cellular factories achieve the many goals, and more, that we have set out for our imaginary factory? The central dogma states that the instructions that determine and guide the structure, development, and internal processes of a living cell are contained in a unique and beautiful informational molecule called "deoxyribonucleic acid," abbreviated as DNA. DNA is the molecular equivalent of our master blueprints, containing all of the information required to build and operate the cell. Beyond that, the DNA contains all of the information needed to assure that every individual cell can maintain itself in right relation to surrounding cells. Adding to this complexity, these groups of cells must be able to interact with other groups to form tissues, organs, and organisms. And, in turn, these organisms must be able to interact with and respond to their environment.

DNA provides an extraordinarily efficient and compact means of storing and replicating information. It has been estimated that the information packed into the DNA of each one of our cells is the equivalent of about 200 encyclopedia volumes! The molecular blueprint for our cellular factory is enormously complex, and complete.

There are elaborate repair mechanisms in place to assist in maintaining the quality and integrity of our DNA blueprints. And, amazingly, these DNA molecules have the ability to make precise copies of themselves allowing growth as one cell divides into two cells. As a consequence each cell retains an absolutely complete set of molecular instructions for its own processes and growth (see below - DNA structure and the molecular basis of inheritance).

RNA - Our Molecular Shop Drawings

DNA is preserved in the nucleus of the cell while most of the ongoing operations and processes of the cell occur outside the nucleus, in an area loosely termed the "cytoplasm." It is in the cytoplasm that new structural components are built and new specialized "molecular machines" are fabricated.

Information is transmitted from the nuclear blueprint to the cytoplasm by means of a second kind of nucleic acid. This second nucleic acid, termed "ribonucleic acid" (RNA) is made by "copying" a small portion of the molecular structure of DNA. These RNA molecules serve as messengers, and for that reason are termed messenger RNA, or mRNA. The mRNA molecule, while a copy of a portion of the DNA molecule, is chemically different. This assures that our mRNA "shop drawings" will never become confused with the master "blueprint" DNA that produced it.

The mRNA molecules move from the nucleus to the cytoplasm where a complex process takes over, translating the information in the mRNA into the working structures of the cell. These structures are largely, usually completely, made of protein. The assembly of these proteins, a process known as protein synthesis, is the process that converts the information contained in our blueprints and shop drawings into the three dimensional structures of the cell and all of its component parts.

A 3D model of the icosahedral capsid of the rhinovirus -
the virus which causes the common cold.

In addition to being the smallest forms of life, viruses are also the most efficient, with the minimum amount of substance and genetic material needed to maintain their existence. Because viruses rely on host cells to provide the complex processes that support life, they need to store only a little information in their genetic material. The smallest recognized viruses, the aforementioned viroids and virusoids, are nothing more than a single strand of DNA or RNA, sometimes only 200-300 nucleotides long. A typical virus might contain only about 9000 nucleotides (a few complex viruses can have up to 100,000 or more), whereas human DNA is over 3 billion nucleotides long . Said another way, a typical virus's DNA could be abbreviated in one-letter sequences in the space of a few pages of this web site - a human's would comprise more than 500,000 pages.

DNA is most frequently found as two strands wound together into the familiar double helix shape. However, some viruses can have only a single strand of DNA. In addition, viruses are the only organisms which can use RNA to contain their genetic information - all other classes of organisms use DNA. These viruses are known as the RNA viruses - the consequences of this will be made clear in a subsequent section dedicated to the RNA viruses. The gene functions of viruses basically fall into two categories - those which carry out a particular stage in the virus's life cycle (cell penetration, latency, or replication), and those used to copy its genetic material and repackage it in new viruses.

Capsomeres attract each other in a certain pattern. The capsomeres of the tobacco mosaic virus form into a spiral.

Almost all viruses (excepting the viroids and virusoids) surround their DNA or RNA with a protective coat, known as a capsid, which is built from simple proteins. The function of the capsid is to shield the sensitive genetic material from attack or alteration, and to help the virus locate and infect a host.

The virus's genetic information contains information for building the proteins which comprise the capsid. Individual proteins fit together like the pieces of a puzzle to form a building block called a capsomere.

Capsomeres self-assemble to form the cylindrical shell of the tobacco mosaic virus.

Capsomeres are designed to attract each other and fit together in a certain way. When enough capsomeres are brought together, they self-assemble into a completed capsid that partially or fully encapsulates the virus's DNA or RNA. The assembled particle is known as a nucleocapsid.

Virus's capsids occur in a variety of shapes and sizes. The tobacco mosaic virus uses capsomeres that stack together in an ascending spiral, forming a hollow cylinder with the genetic material contained inside. Most viruses' capsomeres (including hepatitis C) assemble into icosahedral (twenty-sided) crystalline forms that form a sphere encapsulating the genetic material. These viruses are particularly efficient in their form; the icosahedral shape is the most efficient shape that can be built from the smallest capsomeres, conserving host cell energy for the production of viruses.

Electron micrograph showing viruses aggregating into a crystalline pattern inside a cell.

More complex viruses like hepatitis C surround their nuclecapsid with an additional envelope of lipid (fatty material), extruding only a few of their viral proteins through the envelope. The completed package is called a virion or viral particle - a mature, infective virus.

Even complex viruses are extremely small - most human viruses are less than 150 nanometers in diameter. Hepatitis C is only about 50 nanometers in diameter. A nanometer is one billionth of a meter - if you could put 200,000 Hepatitis C viruses end to end, they would be only a single centimeter long.