The Virus: The Accidental Organism

As science continues to progress, our understanding of life is evolving, thanks in part to the advances in molecular biology. Scientists can now take a closer look at organisms than ever before. Not only has the Linnaean classification system (Kingdom, Phylum, Class, Order, Family, Genus, Species) gone out of favovirus 2r with many scientists due to the molecular unraveling of evolutionary histories of the species, but also the idea of what constitutes a living organism has been put on trial.

Living organisms grow, reproduce, and carry on biological processes within their cells. From the more complex organisms, such as mammals, to the one celled paramecium, life processes are conducted throughout the growing species’ lifetime. Viruses represent that unique biological entity bordering on the threshold of life. It has long been established that viruses exhibit none of the characteristics mentioned above, and the molecular study of them has begged the question are viruses alive?

In order to address this question, let’s first take a look at the structure of a virus. All viruses contain two things: a genome and a capsid (the protein coat that surrounds the genome). The genome can be DNA or RNA, single-stranded or double-stranded. The capsid varies in shape from rod-shaped to a more complex icosahedron. Although a few viruses contain unique enzymes, most viruses contain nothing else. Some viruses are surrounded by a lipid bilayer containing glycoproteins. These glycoproteins bind to specific receptors on the surface of the host cell, making the virus cell specific. Viruses that do not contain a lipid bilayer may have glycoproteins attached to the capsid. The binding of the virus via its glycoprotein to the host cell’s receptor initiates entry of the virus into the cell.

Viruses are obligate intracellular parasites, that is they can only survive within the cell. They have no cytoplasm, no nucleus, no mitochondria or other cellular organelles. They are incapable of making their own energy or manufacturing proteins. The virus relies on the host cell’s proteins/enzymes, ribosomes, and energy to replicate its DNA/RNA and to manufacture its capsid proteins, which are translated from its own genome. Viruses are assembled within the host cell from preformed components. They require no nutrition. Because of this, the virus exhibits no change during its life time. From the moment it forms and buds from the host cell, to the time of its “uncoating” in the next cell it infects, it is exactly the same.

One may wonder where these submicroscopic entities come from in the first place? There is speculation that they arose from life forms that have lost cellular functions. Another theory, and the one I support, is that viruses evolved as a result of the macromolecule (DNA or RNA)  escaping the confines of the cell. Viruses range in size from 20nm – several thousand nm. Their genome ranges from ~6kb (about 10 genes) to ~1.2 Mbp as seen in the Mimivirus (possibly >900 genes). This is small compared to the genome of living organisms (E. coli >5,000 genes, humans ~21,000 genes). The Mimivirus is unique in that many scientists consider it a bridge between the nonliving virus and living organisms.

The question whether the virus is living or not will be under debate for some time. There is still much to learn about the submicroscopic organisms, and until we unravel the mysteries, these small, seemingly non-living particles will continue to infect and destroy their hosts. Many of the nucleic acids found in viruses have the propensity to integrate into the hosts’ genomes and are responsible for the onset of many cancers, a topic for another day. Make no mistakes, the virus is the perfect vehicle for transporting unwanted DNA or, as in the case of the HIV virus, RNA throughout the body.

virus binding

To Barbecue, or not to Barbecue.

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Summer is finally upon us. After weeks of rain and unpredictable weather, we are now able to enjoy those favorite summer activities. Swimming, biking, kayaking, …and oh, let’s not forget the barbecue. What a more perfect way to spend with family and friends than to be outdoors cooking on the grill. But make no mistakes, there are health issues to consider before you fire-up that grill.

It has been well established that cooking meat on the grill is dangerous for your health. Deadly, as a matter of fact. A high consumption of meat that has been cooked over an open flame or on grills that use hydrocarbons does indeed contribute to the onset of cancer. Studies have shown an increase in colon cancers in persons who eat food cooked in this way. Why is this, and what is the culprit?

Before I answer those questions, it’s important to understand the nature of cancer. Cancer is not a single disease. There is an enormous number of genes whose alteration will initiate cancer in a particular cell type. Processes within a normal cell are highly regulated. The highly ordered sequence of events in the life of a cell is called the cell cycle. Within this cycle, there are signals that tell cells when to grow, divide and die. If these signals are altered, the cell cycle becomes unregulated and cancer ensues.

Cancer starts with a mutation in DNA. The induction of the mutation varies depending on the carcinogen (radiation, chemical, biological or endogenous). Among the most common include DNA insertions or deletions, breaks, dimers, and the addition of adducts to a DNA strand. DNA replication proteins become confused by these changes and replicate the DNA strand erroneously. As a result, the protein coded by the mutated gene does not function normally, or the protein becomes silent or absent within the cell.  Sometimes the cell recognizes this abnormality and the DNA is either repaired or the cell dies in the process known as apoptosis. Other times the cell escapes this fate and continues to divide and live longer than it ordinarily would because the protein(s) that once kept it in check are no longer functioning normally. The cell also loses its ability to adhere to other cells and migrates through the body (a process called metastasis).

The cancer causing chemical found in grilled foods is called benzo(a)pyrene (BaP). BaP is a polycyclic aromatic hydrocarbonBaP that forms as a result of incomplete combustion of organic molecules. Simply put, the burning of any organic substance, such as cigarettes, wood, gasoline, meat, may create BaP. When meat is cooked on a grill, molecules normally found in meat can be transformed into BaP. BaP can also be formed from the fuel used by the grill and be carried to the meat with the smoke. As a result, BaP covers grilled meat. Then you eat it. A marshmallow roasted over an open flame also contains BaP.

BaP is not as harmful to humans as its metabolites. BaP enters the blood stream, and once it enters a cell it is converted to other compounds by specific enzymes. The resulting metabolites bind to DNA, forming large adducts that confuse the proteins responsible for DNA replication. Most of the time these adducts are removed through DNA repair mechanisms, but not always. If enough of the adducts remain, the protein coded by the mutated DNA strands does not function normally, or it is simply not transcribed at all. There will then be a cascade of events that triggers the onset of carcinogenesis.

The effects of BaP is cumulative. That is, the more BaP metabolites that bind to DNA, the more likely your chances of getting cancer. It is simply a matter of numbers: it’s more efficient for a DNA repair protein to remove a single adduct from DNA than it is for it to remove a dozen. What this means is that if you absolutely love char grilled food, than eat it. But do so in moderation.

The Nature of DNA

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All living things grow and reproduce, and there must be a blueprint, directions if you will, that enables the organism to carry out these processes and maintain the integrity of the species. That blueprint, in most organisms, is deoxyribonucleic acid, better known as DNA. There are some viruses that do not have DNA, and instead use RNA as their blueprint. HIV is one of them. But many scientists argue that a virus is not a living organism, a topic to be discussed at a later date.

The structure of DNA was elucidated in 1953 by James Watson and Francis Crick. I had the honor of meeting Dr. Watson, the only survivor from that era, and I must say it was like meeting Mic Jagger. Watson stands as a symbol to perhaps the greatest achievement known to science, but make no mistakes, there were others involved in the discovery who never reaped the honors bestowed upon Watson and Crick. Rosalind Franklin deduced the structure of DNA prior to Watson and Crick through her X-ray diffraction photograph. Sadly, she passed away in 1958 at the age of 38 before the Nobel prize was awarded.

So what exactly is DNA? All proteins in the body are coded from DNA through a multistep process. DNA is a polymer, a molecule comprised of repeating similar parts. It is a double-stranded helix containing a series of the 5-carbon sugar deoxyribose, a nitrogenous base and a phosphate group. The phosphate group is what makes DNA acidic.

DNA 1

Let’s take a closer look at the double-stranded structure on the right. The backbone of DNA consists of alternating sugar and phosphate groups. The two strands run antiparellel. The sugar is chemically bonded to a nitrogenous base, which in turn forms hydrogen bonds with its complimentary base, forming complimentary base pairs. There are four different nitrogenous bases in DNA: Adenine (A), Thymine (T), Cytosine (C), and Guanine (G). A always pairs with T, and G always pairs with C. This molecule can replicate itself through a complex series of steps involving enzymes that are coded using its DNA. It’s the replication of this molecule that maintains the integrity of the dividing cell, and ultimately the species. If it were replicated erroneously, then the proteins that are coded from it will be altered, and they will not perform their job very well. As a result, genetic disorders may occur, as well as cancers.

DNA is separated into genes, the unit of hereditary information that codes for one particular protein. It is the sequence of nitrogenous bases, commonly known as the nucleotide sequence, that denotes what protein will be translated from that particular gene. Only one strand of the DNA codes for a protein, and that nucleotide sequence must remain constant. For example, a section of the nucleotide sequence that partially codes for a particular DNA repair protein is 5′ – GGC AAT CCT GTC CCC ATC – 3′. 5 Altering just one of these bases (creating a point mutation) may decrease the activity of this protein, or render it nonfunctional. That could be devastating, considering its job is to repair damaged DNA, or it could be beneficial in cases where you want to destroy the cell by way of DNA modulation, as in cancer chemotherapy. If just one point mutation in one particular gene could cause such drastic consequences, it is a wonder the human species is sill thriving. But there are many safeguards in place to circumvent the consequences caused by DNA damage, and that is what makes the cell so fascinating.

The human body is very complex and each cell contains 20,000 – 25,000 genes, and roughly 50 – 250 million base pairs. This is a lot of DNA, but fear not, DNA is efficiently packaged in the nucleus of most cell types (the exception being prokaryotic cells, which include bacteria).  Before cell replication, the genetic material condenses further to form chromosomes. Each chromosome is comprised of a single strand of DNA,  measuring on average 1.5 x 108 base pairs, that is tightly coiled and packaged along with proteins called histones. There are 23 pairs of chromosomes in human somatic cells (any cell except a sperm or egg). That makes 46 chromosomes per cell. Lined up end to end, the DNA in those chromosomes would extend approximately 2 meters in length. Not bad for a string of molecules.

histones

The understanding of DNA has come a long way from the days of Watson and Crick, but we still have miles to go until we fully unravel this marvelous structure.