You Got Virus In My Fungus!

You got Virus in my Fungus!
May 13, 2016

There are more than 90,000 species of fungus on Earth. They can live on land, in the water and in the air. Fungi can be among the largest organisms on Earth, they can add unique flavor to a good cheeseburger and they even have the capability of mind control.

But according to new research from Duke and Stanford Universities, fungi may not have had the evolutionary power to grow into a whole kingdom of organisms if not for a virus.

Cordyceps Fungus in AntSpecifically, Duke assistant biology professor and study co-author Nicholas Buchler and his colleagues found that the suite of proteins responsible for creating fungal spores, invading other organisms and other essential fungal functions trace back to a viral infection millions of years ago.

Without that infection, Buchler says, the fungal kingdom might not be what it is today.

When organisms are small, they can pick up extra pieces relatively easily. In fact, some scientists think the mitochondrion—the power plant of the cells, common to virtually every complex organism on Earth—may have started as its own cell that a bigger cell ate billions of years ago, and passed down to its kids.

Viruses make that process even easier because they actively try to integrate into cells and use them to make more viruses. The viruses essentially give their genetic material to the cells and trick the cells into copying it.

In this case, Buchler says, the ancient fungus held onto some of that viral genetic material.

So how did they figure this out? It began with a puzzle over the proteins that control how fungal cells divide. The biology of growth, cell division and cell replication is precisely controlled to the extreme. Grow and divide too quickly and you wind up with an organism that cannot eat enough to sustain that growth or cancer. Grow and divide too slowly and maturity and reproduction will never happen.

Every organism has a group of proteins that control when a cell will begin to copy its DNA so it can replicate. In plants and animals, these proteins are called E2F transcription factors (they are currently the subject of a lot of research because E2F transcription factor malfunctions are associated with cancer). 

Fungi, however, have a different protein called an SBF transcription factor. You might be wondering why that matters. After all, fungi represent a whole kingdom of organisms distinct from the plant kingdom and the animal kingdom. They are different from us in many ways.

The issue is that outside the animal kingdom, fungi are actually our closest relatives: closer than the tiny, single-celled organisms and even the plants. Fungi were on the same branch of the evolutionary tree as animals for longer than any other kingdom. It’s fishy, then, that fungal proteins governing such a basic and essential part of life as cell replication are different from ours, especially when we share those proteins with our more distant relatives like plants.

MushroomBuchler and his colleagues, therefore, began searching other organisms for SBF, thinking they might get a clue as to how it wound up in fungi if they found it somewhere else. They combed through the genomes of everything from amoebas to algae, the only requirement being the organism’s cells had internal organs like a nucleus. Hundreds of genomes later, they had not seen a single SBF.

Where they did find it was in viruses, suggesting that sometime after fungi and animals split from each other about a billion years ago, an ancient ancestor of today’s fungi was attacked by a virus, and somehow, instead of driving the ancient fungus to its doom, the virus’s SBF protein gave this particular fungus a competitive advantage over its neighbors. They published their findings in the journal ELife.

What most likely began as an attempt to manipulate the ancient fungus into reproducing quickly and making more viruses, ended with that ancient fungus outcompeting all of its relatives and passing SBF down for billions of generations to create the prolific and diverse kingdom we know today.

These types of events are rare, but they do happen. Scientists call it horizontal gene transfer (as opposed to vertical gene transfer where you get genes from your parents). Bacteria and other tiny organisms swap genes with each other on a somewhat regular basis, which is one way resistant infections grow.

Picking up a good gene from a virus, however, is rare, so future research will tap into how the ancient fungus was able to not only survive the viral attack, but also thrive long after, as viruses will, for the most part, work their host cells until they die.

One way researchers can tackle that question is by looking at the fungi that branched off from the rest of the kingdom early. Some of these most distant fungal cousins are thought to use both E2F and SBF in division. This would suggest that fungi gradually introduced SBF into their own machinery, which would give the fungi a better chance of gradually adapting to the foreign protein.

While research like this may seem to be a little in the weeds, or in this case, in the mushrooms, knowing where SBF came from could save millions of lives and billions of dollars.

Fungal infections can be extremely nasty and very tough to fight. There are roughly 300 species of fungus that can infect humans, according to the Centers for Disease Control and Prevention. They range from mild skin and nail infections for which you see TV commercials, to deadly nerve, lung and bloodstream infections that kill up to 1.6 million people every year according to the Global Action Fund for Fungal Infections.

Mold on CornMost of the deadliest infections occur in people with compromised immune systems, cancer or lung problems, but it is still a staggering figure. And while antifungal drugs do exist, they are harder to develop than antibacterial or antiviral drugs because fungi are so similar to animals on a cellular level that drugs designed to kill fungi could harm human cells.

But if SBF was picked up by fungi and only fungi, that leaves a wide-open target for new drugs. Since SBF plays such an important role in fungal growth, infectivity and spread, drugs attacking SBF would be as effective as they are selective.

And the benefits would not stop in medicine. Roughly 85 percent of plant diseases are caused by organisms in the fungus family. Blight can tear through a farmer’s field quickly, destroying crops, losing money for farmers and raising the price of food. But again, SBF-attacking molecules could wipe out the fungal infection and spare the plants.

Viral SBF is a lesson in evolution. Sometimes one simple change or lucky pickup can change the course of tens of thousands of species. Huge changes might be going on now in any number of species, including humans. We may not be able to wait the hundreds of millions of years it would take to see these changes take effect, but if it all starts with one event, we may see that.

—Daniel Lane

Daniel Lane covers science, medicine, engineering and the environment in North Carolina.