JUL 21, 2016 5:18 PM PDT

Viruses are a Powerful Force Driving Evolution in Mammals

WRITTEN BY: Carmen Leitch
Publishing in eLife, researchers at Stanford University have begun to reveal the extent of the influence viruses have had on mammalian evolution. In the study, computational genomic technology was used to find that viruses were the driving force behind 30 percent of all changes to proteins since humans diverged from chimpanzees, and they remarked that this is a conservative estimate.
Aminopeptidase N is a protein that acts as a receptor for coronaviruses, the family of viruses behind recent epidemics of SARS and MERS, among others. / Credit: Image Courtesy of David Enard
Mammals evolve in response to changes in their environments, and do so through random mutations in their DNA. Through serendipity, some of those are beneficial, making an animal a better match to those environmental changes; they are called adaptive mutations.

In the last decade, biologists studying evolution have found lots of adaptive mutations in many locations in mammalian genomes. It led investigators to wonder what could be causing those ubiquitous changes. Because of their pervasive and adaptable nature, and their ability to interact with the genome, viruses have been ideal candidates.

"When you have a pandemic or an epidemic at some point in evolution, the population that is targeted by the virus either adapts, or goes extinct. We knew that, but what really surprised us is the strength and clarity of the pattern we found," explained David Enard, first author of the study and a postdoctoral fellow at Stanford University. "This is the first time that viruses have been shown to have such a strong impact on adaptation."

The work had to begin with finding out what proteins physically interact with viruses. Previous work in the area has focused primarily on proteins of that are part of the body’s immune response, which is to be expected. The team had to carefully examine tens of thousands of research abstracts to develop a list of 1300 potential proteins as participants in a viral interaction. 

"The big advancement here is that it's not only very specialized immune proteins that adapt against viruses," commented Enard. "Pretty much any type of protein that comes into contact with viruses can participate in the adaptation against viruses. It turns out that there is at least as much adaptation outside of the immune response as within it."
Patterns of adaptation to coronaviruses in Aminopeptidase N. This protein has repeatedly adapted during mammalian evolution to evade binding by coronaviruses. (A) BS-REL test results for ANPEP in a tree of 84 mammalian species. (B) Contact surface with PRCV and TGEV on ANPEP structure (PDB 4FYQ). The figure includes visualizations of all the six different faces of ANPEP. / Credit: Image Courtesy of David Enard
Next, algorithms were created to search genomic databases to compare how virus-interacting proteins evolved versus other proteins. The team found that changes occurred three times as much in proteins that interacted with viruses compared with proteins that did not.

"We're all interested in how it is that we and other organisms have evolved, and in the pressures that made us what we are," said lead author Dmitri Petrov, a Professor of Biology and Associate Chair of the Biology Department at Stanford. "The discovery that this constant battle with viruses has shaped us in every aspect -- not just the few proteins that fight infections, but everything -- is profound. All organisms have been living with viruses for billions of years; this work shows that those interactions have affected every part of the cell."

Viruses multiply and disseminate by taking over a host’s cells, so it’s not surprising that they have an even greater influence on cellular changes than environmental conditions or competition from other species. The researchers suggest that these findings could be an explanation for why similar species have different mechanisms for the same biological functions. "This paper is the first with data that is large enough and clean enough to explain a lot of these puzzles in one fell swoop," said Petrov.

The scientists now plan to research viral epidemics of the past, in the hopes they’ll find clues for fighting current diseases. 

Sources: eLife, Science Daily via Genetics Society of America
About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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