A Voyage of Viral Discovery

Richard Dawkins’ Selfish Gene came out 40 years ago, so it is only fitting that I get to write about the most selfish genes of all: viruses. Basically, viruses are pieces of genetic material–either DNA or RNA–surrounded by a protein shell and maybe some lipid membrane. Viruses are not living cells, and they do not fulfill most of the hallmarks of life that many of us learned in middle school: viruses do not catalyze their own chemical
reactions, they are not made up of cells, and they do not reproduce on their own. In order to do the chemical reactions necessary to reproduce and make more copies of themselves, viruses must find a way to put that genetic material that they carry into a living host cell and trick the host into using the code as it would use its own genome. This is how the virus manages to make the host into a veritable virus factory.

Since viruses rely on living cells for almost everything, it has not been easy to study them. In fact, we did not even know that viruses existed until the late 19th century. The first viruses were isolated when scientists studying a pathogen found that they could run infectious material through the smallest available filters without removing the infectious factor. At that point, they just called them “non-filterable agents” and reasoned that they must be extremely small, even smaller than bacteria. Experiments by others in the early and mid-20th century went on to discover that viruses were mostly protein and nucleic acid (RNA or DNA), making them radically different from previously known cellular life.

As biologists, we were pretty late to the virus party–shoot, we pretty much knew what cells were shortly after the first microscopes were built in the 1600s, but it somehow took until the 1800s to know that there was something smaller that could cause disease–so it is no surprise that there is still a lot for us to learn about the tiny “non-filterable agents.” Appropriately, a recent paper in Nature claimed to find over 1000 distinct viruses that are all new to science. To make this discovery, the scientists first had to pick a group of cellular hosts in which to look for viruses. They settled on invertebrates, a diverse group of animals that include everything from insects and squids to sea urchins and earthworms. They also had to decide what type of viruses they would look for, opting to search for RNA viruses, which invade a host using RNA instead of DNA as their genetic material. By collecting and sequencing RNA from over 200 different invertebrate species, they were able to piece together long strands of RNA using the sequencing data and a computer program. However, those long reconstructed strands of RNA did not necessarily come from a virus present within the host. Host cells make their own RNA all of the time using their own DNA as a template. In order to be sure that the piece of RNA they found originated in a virus, they needed a signature that could only be present in a viral RNA. They found that signature in the form of a RNA virus-specific gene called “RNA-dependent RNA polyermase” or RdRp. RNA viruses use RdRp to copy their RNA genome when they invade a host cell, but they have to bring their own as part of their RNA genome; animals just do not have an RdRp. (That is, unless you believe this group that claims to have found a possibly-functional RdRp gene in a bat genome. I hope you will agree with me when I say that living things tend to be amazing because all of the rules we have about them are inevitably broken in some other organism.)

With this handy tool to distinguish viral RNAs from the rest of the pool, the authors had a field day discovering new RNA viruses. In addition to classifying viruses based on the host they were discovered within, they also used a technique known as “phylogenetics” to compare the RNA sequence of all viruses in order to place them on a tree of life relative to each other. Since all life on earth can ultimately trace its root back to one common ancestor that is the evolutionary relative to all of us, from human to bacterium, we can compare the nucleic acid sequences of organisms or viruses in order to infer their evolutionary distance from each other. For example, two viruses with relatively similar RdRp genes would be inferred to be quite closely related compared to a third virus with less sequence in common in the RdRp gene.

These new viruses were not discovered as human pathogens, so it is unlikely that this finding will have any direct medical relevance. This result can instead be useful for ecologists and evolutionary biologists who want to understand the variety of viruses that infect the invertebrates studied. Moreover, since we know quite a lot about the evolutionary relationships between different invertebrates–owing to us having studied them quite intensely for decades or even centuries–we can now use the new phylogenetic information about viral genome relatedness to start to ask questions about how the viruses co-evolved with their hosts. For instance, a group of related beetles may tend to be infected with related RNA viruses. If this is the case, then it is possible that an early ancestor of those RNA viruses made a living infecting an early ancestor of those beetles. Basic studies like that might also help us to someday understand host-virus co-evolution in humans and our viruses. After all, humans are in no danger of hitting an evolutionary brick wall, and neither are our viral foes.

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