Can Studying Viruses Help Us Understand the Evolution of Life?

Guest post by Eugene V. Koonin, PhD, NIH Distinguished Investigator for the Evolutionary Genomics Research Group at the National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health. To view a series of video interviews of Dr. Koonin by Dr. Brennan, please view A Conversation with Eugene Koonin.

The study of the evolution of viruses is a key task for biomedical researchers. In these post-COVID-19 days, this message hardly requires much advocacy—we now intimately know that understanding how viruses evolve is crucial to track and eventually predict the course of epidemics, and this work ultimately helps save lives. But viruses are about much more than human disease; indeed, all organisms on earth, from bacteria to amoeba to plants and animals, are infected by multiple, diverse viruses.

Thanks to a powerful new methodology known as metagenomics—simply put, the sequencing of all DNA or RNA from any environment without growing organisms in the lab—we can now explore the diversity of viruses incomparably better than we possibly could even a decade ago. And that diversity is nothing short of astonishing: a recent estimate my colleagues and I developed using this methodology suggests that there could be as many as a billion distinct virus species on our planet.

My group has been studying the evolution of viruses for years, and one of the fascinating questions we asked was, if we compare the rapidly expanding diversity of known viruses that infect all kinds of organisms, might it be possible to peer into the distant past and figure out what viruses were infecting our distant ancestors?

By “distant,” I don’t mean our common ancestors—the ones we share with chimpanzees—who walked the earth several million years ago; I mean truly distant ones such as the common ancestor shared by all eukaryotes (organisms made of complex cells that contain a nucleus, including animals, plants, fungi, amoebae, and some other single-celled organisms) that lived two billion years ago.

My colleagues and I addressed this question by reconstructing a virome (the collection of viruses that infect a given host species) of our two-billion-year-old eukaryotic ancestor. To do this, we mapped the current diversity of viruses on the evolutionary tree of life, then applied some simple mathematical methods to infer which of them were already present in that distant common ancestor.

The conclusions were rather remarkable. First, we found that the virome of our ancestor eukaryotes was nearly as complex as that of modern organisms—it seems that as far as viruses are concerned, not much has changed in two billion years.

Second, we found that all viruses that infect eukaryotes evolved from those that infect bacteria. This was unexpected because we know that DNA and RNA synthesis in eukaryotic cells originate from endosymbiosis (a symbiotic relationship where one organism lives inside a cell or a second organism—in this case, that relationship involves bacteria and archaea, prokaryotic cells that lack a nucleus). Considering this, we assumed that eukaryotic viruses would have evolved from viruses of archaea. However, this was not the case—the viruses that infect eukaryotes apparently came from bacteria! What gives?

The answer seems to come from the membranes. Every cell is bounded by a lipid membrane, but while archaea and bacteria have completely different lipid membranes, the membranes of eukaryotes are made from the same lipids as bacteria. Therefore, if at the root of eukaryotes is an archaeon engulfed in a bacterium, the resulting proto-eukaryotic cell would have to somehow replace the membrane. There seems to be no biological precedent for this!

We clearly needed a different model to find the origin of the eukaryotic cell. To address this problem while accounting for some aspects of eukaryotic biochemistry, a different model has been discussed in the literature, one where a bacterium first engulfed an archaeon and the archaeal membrane was thereby lost, and then a second bacterial endosymbiont became the mitochondrion. This model postulates two endosymbiosis events rather than one but avoids the problem of membrane replacement. Our finding that eukaryotic viruses evolved from bacterial viruses seems to strongly favor this two-symbioses model for the origin of eukaryotic cells.

It appears that archaeal viruses were excluded from the emerging eukaryotic cells because the archaeal membranes disappeared, and those archaeal viruses could not penetrate bacterial membranes.

This study of the ancient stages of virus evolution may be able to inform us of some of the key stages in the evolution of cells themselves—arguably, among the most important questions in evolutionary biology.

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