A Natural Mechanism Can Turbocharge Viral Evolution

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The Science

The first step in the deadly dance between a virus and microbial cell is an embrace. For a virus with a “head-tail” morphology, this means using proteins on its tail fibers to latch onto a specific target on the microbial cell’s membrane. Two decades ago, a team discovered a group of viruses that had in their genomes a surprising tool: a “diversity generating retroelement,” or DGR. The DGR could mutate the virus’ tail fiber proteins, and thereby allow them to embrace different cells. Since that discovery, DGRs have been found in other viruses, bacteria, and archaea. But how widely distributed they are, and the roles that they might play in the wild, hasn’t been clear.

Now, to answer these questions, a team led by scientists at the US Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science user facility located at Lawrence Berkeley National Laboratory (Berkeley Lab), has looked for DGRs in a broad range of publicly available datasets. They’ve discovered that DGRs are not only widespread, but also surprisingly active. In viruses, DGRs appear to generate diversity quickly, allowing these viruses to target new microbial prey.

The Impact

This research provides a much more comprehensive understanding of how a fundamental mechanism of evolution — DGRs — allows microbes to adapt to changing environments. It also sheds light on why the rapid injection of mutations in a particular gene might boost an organism’s fitness. Moreover, the discovery of more than 30,000 DGRs in this analysis, a 20-fold increase over what was previously known, throws open the doors to characterizing how DGRs work at the molecular level. Scientists might then harness them as molecular tools for research and industry applications.

Summary

In their recently published Nature Communications article, the team used publicly available data, approximately half of which was generated by the JGI, to uncover these DGRs. DGRs were found in single microbial and viral genomes, as well as genomes sampled all at once from the same environment, called metagenomes.

Why? Simon Roux, who led the research team and is the head of the Viral Genomics group at the JGI, thinks that if you’re a virus or a microbe with a DGR, you gamble every time you mutate. But, perhaps, it works to keep throwing the dice.

There’s some evidence to support the idea. Study coauthor Stephen Nayfach, a JGI bioinformatics research scientist, found that pieces of viruses with DGRs were found, on average, in double the number of microbial genomes. That means that those viruses accessed many more potential microbial cells or hosts.

This ability isn’t enough to make them super viruses, though, said Roux. There’s a gauntlet of other cell defenses that could prevent viruses from successfully replicating, even if they managed to enter the host cell.

DGRs could prove to be powerful tools not only for viruses and other microbes, but for scientists. One emerging industry application of DGRs is to use them to create collections of protein variants, produced in engineered viruses or microbial cells. Researchers could then use these proteins to recognize individual pathogens and pull them out, like fish on a fishing line, without harming the rest of the microbial community. The study’s publicly available dataset gives researchers the opportunity to study how DGRs work and develop more of them into new biological tools.