BEACON Researchers at Work: Going Viral

This week’s BEACON Researchers at Work blog post is by University of Washington graduate student Sonia Singhal.

Photo of SoniaAs a junior in college, I fell in love with viruses.

That September, I joined Dr. Paul Turner’s virus evolution lab. I had chosen to work there in particular because I thought the research would allow me to combine ecology and molecular biology. The Turner lab used viruses to study topics from host jumping to the evolution of sex. Before entering the lab, I had never considered that viruses, like any other creature on the planet, might have their own ecological niches or evolutionary trajectories. I had never considered that we might be able to use patterns of changes in viruses—which, after all, may or may not actually be alive—to infer what might happen in higher organisms.

Instead, I found myself becoming more and more enamored with the viruses themselves. Viruses are full of paradoxes. Although they are not considered “living” by textbook definitions, they have genomes, they hijack other cells (hosts) to propagate themselves, and their genomes change rapidly over time. Such rapid change comes at a high cost: Viruses need to change often enough to find the few helpful mutations, but not so much that they then lose that helpful alteration or become overloaded with harmful mutations.

Fittingly, my project in the Turner lab also involved a paradox. Researchers in the lab had previously evolved a set of viruses to be either genetically robust or genetically non-robust. A virus that is genetically robust will generally not be impacted by mutations—if its genome changes, it can usually still survive. In contrast, a genetically non-robust virus that gains a mutation in its genome will probably not survive.

Now, one of the debates surrounding genetic robustness is whether robustness would help or hinder evolvability, the ability of the virus to adapt to new conditions. As viruses replicate, errors (mutations) accumulate in the genomes of their offspring. Sometimes, these changes lead to small differences in how well the virus can infect its host, replicate its genetic material, and exit the host. Viruses that do slightly better at any or all of those things are favored, and their numbers accumulate over time. But in the case of a genetically robust population of viruses, mutations will not cause any difference in how well each virus performs. If all viruses are performing equally well, no one lineage of virus can dominate. For this reason, genetic robustness may prevent viruses from evolving (in the sense of changing how exactly they infect, replicate, and burst their host).

However, for the same reason—that mutations cause no difference in performance—the changes that accumulate in the viral genomes are also not removed from the population. Rather than having a population in which each virus’s genome resembles every other virus’s, each virus is genetically distinct. Suppose we then put this diverse population into a completely new environment, where the relationship between genome and survival is not the same as in the original environment. Now some of the viruses cannot infect their host, they cannot hijack its replication machinery, or they cannot burst it. These viruses die out. But other viruses that happen to have an advantageous mutation do very well. They propagate, and they start to gain additional mutations that increase their advantage. In this way, genetic robustness might actually lead to evolvability: The final population of viruses does not look or behave in the same way as the original population.

When the researchers in the Turner lab exposed their genetically robust and genetically non-robust viruses to a higher temperature (20 deg. C higher than what the viruses are used to), they found that the robust viruses adapted more quickly to that high temperature than the non-robust viruses. In fact, at moderately high temperatures, the robust viruses immediately survive better than the non-robust viruses. So in this type of environment, robustness seems to promote evolvability. I was curious whether the advantage of the robust viruses would hold in other environments. If I put the viruses on a new type of host, would the robust viruses initially do better than the non-robust viruses? Would they adapt to that new host more quickly than the non-robust viruses?

I only got to carry out the first question during my time with the Turner lab. I tested the viruses’ initial survival on different cell types. The short answer to my question was no, the robust viruses did not perform any better than the non-robust viruses. Their advantage is probably specific to changes in temperature. However, by that point, my love affair was already well underway. I was hooked by the power of these microscopic particles to teach us about deep principles of evolution. I applied to do graduate work in experimental evolution—to use microbes and viruses to study evolution in real time—and am currently part of Dr. Ben Kerr’s lab at the University of Washington, where I hope to continue exploring questions on robustness and evolvability in viruses. 

My love affair with virus evolution has taken me places that, as an undergraduate, I never imagined I would go. I feel that the evolutionary trajectory of my academic career hinged on my work in the Turner lab. After completing my undergraduate degree, I lived for a year among the Roman ruins in Southern France determining the genome sequence of a plant virus. I spent this past summer in the supreme silence of the San Juan Islands learning about marine viruses. As a result of that course, I traveled to the beaches of Búzios, Brazil, where cactuses grow next to the ocean on volcanic rock, to present some of the research we did. But most exciting is the rich intellectual pasture I have found in the complicated concepts that virus evolution can help start to answer.

My evolutionary journey is still young, but I am eager to see where it will take me.

For more information about Sonia’s work, you can contact her at singhal at uw dot edu. 

About Danielle Whittaker

Danielle J. Whittaker, Ph.D. Managing Director of BEACON
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