Since the first discovery of virus by Martinus Beijerinck in 1898, viruses have been classified in a number of different ways. First, viruses were considered a poison, then a life-form, next demoted to classification as a biological chemical, and finally correctly characterized as non-living organic matter. Their current classification is based on three tenets of life that viruses don’t exhibit – the ability to synthesize proteins, the ability to produce energy, and the ability to divide. All organisms from the three domains of life, Archaea, Bacteria, and Eukarya (Fig. 1), perform these functions, and since viruses do not, they are not considered to be living. While the classification of viruses as non-living is not in danger of changing anytime soon, recent discoveries are beginning to change the way scientists think about viruses and their origins.


Figure 1. The three domains of life are classified based on their evolutionary relationship, Eukarya are organisms whose cells have a nucleus, and they can be either single-celled (e.g. protozoa) or multicellular (e.g., plants, animals, fungi). On the other hand, Archaea and Bacteria are single-celled organisms that do not have a nucleus. Image from OpenStax College, “Organizing Life on Earth” <http://cnx.org/content/m44588/latest/?collection=col11448/latest>

The discovery of giant viruses


Figure 2. Bacteriophage, a virus that infects bacteria. Image from The Database Center for Life Science via Wikimedia Commons <http://commons.wikimedia.org/wiki/File:Bacteriophage.png>

When a person thinks of a virus, he or she may picture a high school or college textbook image of a bacteriophage, a type virus that infects bacteria (Fig. 2). These spaceship-shaped viruses are about 10 to 100 times smaller than the bacteria that they infect and can not be seen even by a light microscope. For further perspectives of how small viruses really are, it is estimated that half a million bacteria can fit on the period at the end of this sentence. This means that 5 million to 50 million bacteriophages could fit on the same period. While viruses come in all shapes and sizes, the majority is incredibly small, like the bacteriophage. Ten years ago, a giant virus was serendipitously found after it had mistakenly thought to be a bacterium. Due to its incredible size and ability to be seen by light microscope, this virus (named Mimivirus for “microbe mimicking” virus) changed how scientists thought about the upper limits of the viral world.

As Mimivirus was found in the water dwelling organism, amoeba, virus hunters such as Jean-Michel Claverie at Aix-Marsaille Univeristy have been collecting water samples from around the world in search of other textbook-changing viruses. Their search has most recently led to the discovery of the largest viruses ever characterized, the Pandoraviruses. The first of these giant viruses, Pandoravirus salinus, was isolated from sediments at the mouth of a river off the coast of Chile. The second, Pandoravirus dulcis, was collected in a pond near Melbourne, Australia. They determined the size of these viruses to be about that of a small bacterium. For comparison, see Figure 3 below, which depicts the relative sizes of various biological matter in logarithm scale (i.e. neighboring tick marks represent 10 times difference in size).


Figure 3. Relative sizes of relevant biological matter in size increments of 10 and their ability to be detected by different forms of microscopy. Image from OpenStax College, “Organizing Life on Earth” <http://cnx.org/content/m44406/latest/?collection=col11448/latest>

After this, Claverie and colleagues went on to characterize the genome of each virus. The genome contains the hereditary information of an organism. This information is encoded in DNA in most organisms (although some viruses have a RNA genome). DNA is a long, macromolecule made up of subunits called “bases”. A sequence of bases represents genes, which contain the information that can be translated into proteins. Generally, the longer the genome sequence in bases, the more genes, and the more functions the organism or virus is able to carry out. Although viruses cannot synthesize proteins themselves, they can harness their hosts’ cellular machinery to translate their genes into viral proteins. These viral proteins are then assembled into new copies of viruses.

Claverie and colleagues purified the viral DNA and found genomes of at least 2.5 million bases for P. salinus and at least 1.9 million bases for P. dulcis – the largest viral genomes discovered to date and at least 600,000 bases longer than the previous record holder [1]. Further, it is estimated that the genome of P. salinus contains 2556 genes. For comparison, the genome of HIV contains only about 10,000 bases and 9 genes while the human genome contains about 3 billion bases and somewhere between 20 and 30 thousand genes. The genome size of these viruses is comparable to some protozoa (single-celled eukarya) and bacteria, and they encode for many proteins that are not common in most viruses. While large genome sizes do not mean that these viruses are capable of functions attributable to protozoa or bacteria, it does show that these viruses are inherently complex and raises questions about their origins.

Descendants of a fourth domain of life?

To make things even more interesting, 93% of the genes in the P. salinus genome bear no resemblance to any viral, bacterial, or eukaryotic genes ever identified [2]. Thus scientists postulate that these viruses may have a unique origin separate from other viruses and the three recognized domains of life. Thinking that this interpretation could open up a pandora’s box regarding the evolution of life is in part why the authors decided on the name Pandoravirus [3]. To understand the unique origin of pandoraviruses a bit better, let’s look specifically at the gene encoding a protein called DNA polymerase.

DNA polymerase is found in every cell and some viruses, and performs the essential function of replicating DNA when cells divide. Organisms within each domain of life have unique DNA polymerases that are different from those found in other domains. It is believed that these proteins have evolved independently in each domain, meaning that DNA polymerase was not present in a common ancestor to all of the domains, but rather it developed in each domain on its own due to its necessary evolutionary advantage. The Pandoraviruses and other recently discovered giant viruses contain DNA polymerases that are unique from those seen in other organisms and viruses, demonstrating the uniqueness of these viruses.

Now the million-dollar question will be: where did these viruses come from? Some scientists suggest that these viruses might be remnants of a past fourth domain of life that have degenerated into the parasites they are now. We generally think of evolutionary forces as driving organisms to become more complex, but if encoding fewer functions and parasitizing a host provided an organism with a greater ability to pass on its genes, such changes could be acted on by natural selection. However, this will be difficult to prove without evidence of cellular organisms of this hypothesized fourth domain.

Regardless of their origin, the discovery of Pandoraviruses serves as a reminder that the upper limits of our scientific knowledge are constantly being remodeled. Future studies may bring us even more complex viruses that will make us question our understanding of viruses and life even more. The fact that the Pandoraviruses were found in two different parts of the world leads scientists to speculate that other wonders of the viral world may be out there waiting to be discovered. Scientists can only guess whether or not new discoveries will continue to challenge what we believe about viruses, but as long as they keep looking, we are sure to be surprised.

Joe Timpona is a PhD student in the Virology Program.

References:

[1] Ed Yong, “Giant viruses open Pandora’s box” Nature News. July 18, 2013. http://www.nature.com/news/giant-viruses-open-pandora-s-box-1.13410

[2] Vincent Racaniello, “Pandoravirus, bigger and unlike anything seen before” virology blog. August 1, 2013. http://www.virology.ws/2013/08/01/pandoravirus-bigger-and-unlike-anything-seen-before/

[3] Stuart Weston, “Pandora’s box is viral” Stuart’s Science. October 7, 2013. http://stuarts-science.blogspot.co.uk/2013/10/pandoras-box-is-viral.html

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