Virolution. Frank Ryan

a good question. Some people will argue that viruses are not life. I disagree with that, certainly. Perhaps a more pertinent question to me is not “what is a virus?” but “what is a species as far as a virus goes?” Are there species of viruses analogous to mammalian species? Basically I am only recently into viruses. I became interested, almost accidentally, because of the work we do with mammals. It just happens that mammals are the main reservoirs of these viruses. So for me the question “what is a species when it comes to viruses?” is best understood in the context, are they evolving, and are they co-evolving with their reservoir organism? I think that viruses are lineages that have their own evolutionary trajectory and their own historical fate. By analysing the history of that evolution and studying the branching patterns of those viral lineages, we can define viruses based on the branches of the tree. And when we look across the board at these hantaviruses, our evolutionary analysis thus far has shown a very tight correlation between the evolutionary tree that illustrates the history of the mammalian host and the evolutionary tree that illustrates the history of the viruses.’

      This still made little sense to me in the way I had been educated to think about viruses, not from the medical perspective and not, as I was already beginning to suspect, from the evolutionary perspective.

      ‘When you say you are studying the virus, do you imply studying its genome?’

      Here I should explain, for my non-scientific readers, that a genome is the sum total of all the genes of a life form. While all other forms of life, including humans, have genes coded by DNA, viruses can be coded by DNA or, as in the case of the hantaviruses, by its sister molecule, RNA.

      ‘Studying its genome,’ he confirmed, ‘or any other characters that would be applicable. They are such simple organisms that – for example, in the case of hantavirus – to get enough characters to be able to understand the evolution of the virus, the best thing to use is the RNA sequences. So we’re having better luck with this because each of the bases in the RNA sequences is applicable.’

      ‘How do you manage to do that? Have you been studying the viral genome as and from when you first noticed it, or have you some way of going back in time to see what the virus was like some time ago?’

      ‘That’s a complicated subject and one that has been debated at the Natural History Museum at the exhibit on the evolution of man. We use a methodology called Cladistics. It’s basically a phylogenetic analysis [tree of life analysis] of the different lineages of viruses.’

      ‘This is where you observe them in different species?’

      ‘Not exactly, no. We’re talking about [analysing sequences over] enormous periods of time here. We have been successful in extracting viruses from our frozen tissue collection and we are having success with extracting DNA from fossil organisms. People have successfully amplified and sequenced DNA from plants that were embedded in Miocene rocks – these are 30-million-year-old plants. So what you can do with this phylogenetic analysis is take a viral sequence from a hantavirus of the Four-Corners deer mouse and compare that to other species of viruses that occur on other branches [of the parallel virus-rodent trees]. From this you can extrapolate what the historical condition was. So we can trace the evolutionary sequence back in time and make comparisons to other lineages that diverged from the lineage you are interested in, much earlier in time.’

      The implications were slowly dawning on me. ‘So you see a link between the virus and the mammal that is very close?’

      ‘That’s right. For example, if we were looking at eutherian mammals [the placental mammals including humans], we might compare the sequences of eutherian viruses to those of the marsupials and egg-laying mammals, which are more ancient.’

      ‘Because they are similar, but not the same viruses, you raise the question that sometime in the past, just as the animals had a common ancestry, perhaps their viruses might also have had their own common ancestry?’

      ‘That’s right.’

      A surprising idea had entered my mind. From my background knowledge of evolutionary biology, and in particular of evolutionary virology, I could assume that virologists, sharing the same conventional viewpoint as I had up to now, would assume that the viruses, given that they mutate at a vastly faster rate than the mammals, would fast-track their own evolutionary trajectories, to stay close to the evolutionary pathways of their mammalian hosts. But now, thanks to the surprising idea that Terry Yates had planted in my mind, I asked myself the question:

      What if both the virus and its mammalian host are influencing one another’s evolution, one evolutionary tree interacting with the other, over the vast time periods of their co-evolution?

      I spent a good deal longer than I had initially envisaged with Professor Yates, visiting the Sevilleta and enjoying the courtesy of a stay with him and his family, when I had ample opportunity to examine his work, and to think about his ideas in more detail. When I put my question to Yates himself, he could provide no definite answers other than the observation that viruses and hosts appeared to be following very close co-evolutionary trajectories. Nevertheless, over the months that followed, his explanation of virus-mammalian co-evolution intrigued me deeply and it caused me to look much harder at the relationships between viruses generally and their hosts. In particular I spoke to other biologists, and especially virologists, and I explored the literature far and wide. As far as I could determine, nobody was even thinking along the lines of viruses and hosts influencing each other’s evolution. And thus it would appear that, entirely by chance, I had stumbled across an idea that, if true, would have major implications. It was one of those exciting moments a scientist hopes will come along at some stage of his or her career, a new idea that makes you think long and hard, and even to question some of those ordinary assumptions you have carried with you since your undergraduate years.

      What, then, is a virus?

      Biologists will differ very widely in their answers to this question. Some will quote the distinguished immunologist and writer, Sir Peter Medawar, Nobel Laureate for his work on tissue transplantation, who caricatured the virus as a piece of bad news wrapped in a protein. But this definition, however whimsical, adds little to any real understanding. Others, usually molecular biologists or geneticists, will adopt a chemical perspective, while Darwinian evolutionists – and until recently symbiologists too – are inclined to see viruses as mere agents of “horizontal gene transfer” between different species. We saw a very interesting example of this with Elysia chlorotica, when the strange retroviruses in the slug’s genome appeared to enable the transfer of key genes “horizontally” across the kingdoms of plants and animals, as represented by the alga and the slug. Another interesting perspective is that of Eckard Wimmer, a professor in the Department of Molecular Genetics and Microbiology at Stony Brook, New York, who became famous in 2002 for reconstructing the polio virus from mail-order components back in his lab.⁶ This experiment provoked a good deal of interest and notoriety. But what Wimmer and his co-workers wanted to do, amongst other things, was to make a conceptual, and perhaps philosophical, point. If you know the genetic formula of a virus, you can reconstruct it. They even quoted an empirical formula for the polio virus, as follows:

      C332,652H492,388N98,245O131,196P7,501S2,340

      It is strange to think of an organism, even if exceedingly small, being reduced to a list of atoms. One is reminded of the bitter opposition of the gentle French naturalist, Jean-Henri Fabre, the so-called poet of entomology, who, although he greatly respected Darwin as a man and fellow scientist, opposed Darwin’s line of thinking. In Chapter VIII of his book, More Hunting Wasps, Fabre described a ‘nasty and seemingly futile’ experiment he had conducted, rearing caterpillar-eating wasps on a ‘skewerful of spiders’. We need not consider the experiment in detail here, only Fabre’s conclusion, which led him to dismiss the concept of evolution through natural selection. In Fabre’s own words, ‘It is assuredly a majestic enterprise, commensurate with man’s immense ambitions, to seek to pour the universe into the mould of a formula … But … in short, I prefer to believe that the theory of evolution is powerless to