Living through a pandemic means thinking of viruses like COVID-19 as threats. But sometimes microorganisms can actually be beneficial to human biology. Nels Elde is an evolutionary geneticist at the University of Utah and this month he received a prestigious MacArthur Fellowship — the so-called "genius" grant. He joined Caroline Ballard to explain how some functions of our bodies are born from our interactions with viruses.
This interview has been edited for length and clarity.
Caroline Ballard: We think of microorganisms as foreign invaders that attack our body. But you’re looking at when they actually become part of our body. How does that happen?
Nels Elde: We often think about infectious microbes as invaders — things that we are battling, and that's true. We're stepping through that now with a current global pandemic. But if we look at what have been the outcomes of these infections over a longer timeframe — not just sort of the last year but hundreds of thousands of years or even longer — there are kinds of viruses, retroviruses: the ancestors of things like HIV. As part of the way they replicate, they actually insert genetic material into our genome. And because that's part of our genome, now it's carried from generation to generation. What we and some other labs have begun to discover is how these relic viruses are making contributions to our own biology today.
There's cases where these viruses are actually influencing our immune responses to natural infections, or they're contributing in really interesting ways to some of our most fundamental biology. The fact that we're mammals is defined in part because of the female's placenta, and in fact, some of the key functions of the placenta are donated from some of these ancient viruses.
CB: How does that happen? Can you explain that a little?
NE:It's pretty wild. There's something called an envelope gene. It's a key part of when a virus particle gains access to our cell. The virus itself has to fuse with the infected cell to gain access to our genome, to replicate and make more viruses. Some copies of this gene, the envelope gene, have ended up in our genome and now have been repurposed, in a sense. What these genes do is they encode the very same function, but instead of fusing a virus particle to a cell, they're fusing the cells of the developing placenta to allow it to become viable. An outcome of the infection is that our biology has now been enhanced or changed in a beneficial way.
CB: Are there other examples of where a virus has defined how we function?
NE: One of my colleagues at the University of Utah, Jason Shepherd, has discovered a gene called Arc [which] also has sort of a viral origin. It's involved today in our memory. So you take away the gene in mice, for example, and you can see deficits in memory. And so past encounters with things like viruses have really influenced some of our core biology that we depend on every day.
CB: The average person gets sick with a cold or the flu maybe a couple times a year throughout their entire lives. How common is it for a virus to become part of someone's genome and eventually, maybe become beneficial?
NE: Those events are super rare. But when you start to look at them, not over the course of the flu season, but over the course of hundreds of thousands of years or even longer, even these rare events can start to stack up over time.
CB: You often think of evolution as taking place on that macro timescale, millions of years. We are in a global pandemic and it does feel pressing. Can you speed up that process of viruses becoming a good thing for our biology?
NE: Viruses are massive populations — high mutation rates in short generation times. And so, evolution of our immune systems can seem to take a really long time, whereas evolution of a virus population can happen in the blink of an eye. It can seem scary, “Is this thing evolving to become some sort of super virus?” There are actually reasons to take a bigger view, and this is what the evolutionary perspective really offers, because viruses mutate.
In the case of the coronavirus, the most consequential genetic event probably happened about a year ago before it had spilled over into human populations, potentially from bats. And this is a question that evolutionary biologists are racing to try to understand: what were the genetic changes that allowed this virus to spill over and merge in our own population?
CB: When it comes to fighting COVID-19, where does your research fit in?
NE: There is a postdoc fellow in my lab, Stephen Goldstein, who is an expert in coronaviruses, and now he's using this opportunity to take an evolutionary perspective — to step back and ask about not just SARS-CoV-2, the one that causes COVID-19, but sort of the whole family tree of coronaviruses.
It's an incredibly diverse class of viruses that infects not only humans and bats, but also livestock and rodents. It's almost like separate stories that we can compare about the diversification of coronaviruses to try to understand the rules by which they mutate and then may become new infectious agents, and maybe pandemics of the future.
