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Why we cannot ignore the place of viruses on the ‘Tree of Life’

By Dr Hugh Harris, APC Microbiome Ireland/University College Cork

Image: Corona Borealis Studio/Shutterstock

One particular virus has come to dominate our lives. Now Dr Hugh Harris of APC Microbiome Ireland and University College Cork writes that viruses deserve a place on the ‘Tree of Life’.

A single virus has dramatically changed our lives.

SARS-CoV-2 is keeping most of us at home, often with other members of our family. The next time we get annoyed by a relative, some perspective might be achieved by thinking about how inclusive the concept of family can be.

A family tree is a familiar sight to many people. There is something intriguing and even nostalgic about looking into the past, beyond our parents and grandparents. We all want to know where we came from.

How far back do the branches of kinship reach? A visit to the zoo might have us looking at the chimpanzees and gorillas as they go about their day – these are our cousins.

Richard Dawkins described a thought experiment where a female chimpanzee held the hand of her mother. The mother, in turn, held the hand of her own mother and so on back across the generations, forming an unbroken chain stretching into prehistory. We can imagine a human female holding the hand of her ancestry in the same way, gradually becoming more ape-like as millennia roll by. There will come a point when both lineages meet their shared common ancestor in Africa, between 5m and 7m years ago.

‘The next time you get food poisoning, take solace in knowing that a distant cousin is responsible for your misery.’

Thought experiments are always deliberate oversimplifications, but animals holding hands through time captures the concepts of evolution and shared common ancestry. Modern species are unbroken branches on a great Tree of Life. Broken branches are species that, unfortunately, went extinct.

Are all species related? Does the answer to the question of life and human relatedness ever change from yes to no? Is an oak tree a distant evolutionary relative? Are species of fungus really our cousins?

All cellular life is hypothesized to come from an ancient, single-celled ancestor known as LUCA, the Last Universal Common Ancestor. Even bacteria belong in this model of life, so the next time you get food poisoning, take solace in knowing that a distant cousin is responsible for your misery.

But what about viruses? They exist outside the cells they infect as genetic material enclosed in a protein shell. Are they related to cellular organisms? Are they even alive?

I, along with my co-author Prof Colin Hill, recently wrote a review article in Frontiers in Microbiology discussing the importance of viruses in relation to the rest of life.

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Blurred boundaries between cells and viruses

All cells share fundamental molecular machinery. DNA containing nucleotides is transcribed into a related molecule called RNA, which is then translated into proteins containing amino acids according to a universal genetic code.

This process of translating information stored in RNA into functionally and structurally useful proteins is carried out by the ribosome, a sophisticated apparatus composed of numerous proteins as well as RNA scaffolding.

Viruses lack ribosomes, which is why they infect cells in the first place. They insert their genetic material (either RNA or DNA) into the cell and hijack the translation machinery of the host to make virus proteins involved in building more of themselves.

There is no other way that viruses can multiply – they need access to a ribosome.

The inert, extracellular stage of a virus is called a virion. No one would argue that these structures are alive. Things get complicated however when the virion binds to a receptor on the surface of a host cell and injects its genetic material into the cytoplasm. Viral genes are expressed and metabolism is altered to benefit virus multiplication. This means that the virus is now in control of the ribosome.

We can take this one step further and say that the host cell has now become a virocell. Think of the virus as exploiting the ribosome to switch the strategy of genetic replication that takes place within the cell.

Virion production has usurped cell division as the means of propagating genetic material – the DNA or RNA of the virus. The virocell concept sees the virus as both cellular and alive during this stage of its replication cycle.

The concept of life is a little fuzzy around the edges. Scientists and philosophers love to invent examples and counterexamples to dismantle popular definitions. Viruses will always be confined to the boundaries between living and non-living.

But viruses are also evolving biological entities. Their relationship with other species should have less to do with ‘life’ and more to do with shared evolutionary history.

Image: Lightspring/Shutterstock

The inseparable nature of cells and viruses

Genes jump around. They are not only passed down the generations, but can move within them as well, sometimes being transferred from one species to another. This is a process called horizontal gene transfer (HGT) and it may be as old as life itself.

HGT is a lot more rampant in bacteria. Species rapidly gain and lose genes over evolutionary time, leading to a tangled view of the Tree of Life. Here, a species is not a concrete entity but a collection of genes that swap with other species much like players on a soccer team.

Viruses engage in a form of HGT as well as their more destructive tendency to destroy cells. They do this by adopting a more dormant lifestyle called lysogeny where they insert their DNA into the genome of an infected cell, replicating along with the host through cell division. Occasionally, they can stay this way forever, losing their infectivity and becoming a permanent addition to the host cell.

There is now strong evidence to suggest that viruses existed right back to LUCA and beyond. Patrick Forterre, in a striking metaphor, describes the Tree of Life as being “infected by viruses from the root to the leaves”. It appears that viruses are as inescapable as they are enigmatic.

The story does not end there. As much as 8% of the human genome is composed of virus DNA. We are being continually infected since long before humans were humans. Some of those infections have stuck around. There is even evidence to suggest that the mammalian placenta evolved from an ancient viral infection!

Viruses are more than our cousins. They are an integral part of who we are, intertwined with our very DNA. Life on Earth can hardly get more inclusive than that.

Dr Hugh Harris works with APC Microbiome Ireland at University College Cork (UCC) focused on viruses in the human gut and their role in the gut ecosystem and human health. He has spent more than 3 years as a research assistant in bioinformatics at the School of Microbiology in UCC and is an author on 35 published papers. Harris’ main interests are in data analysis related to microbial biology and evolution.

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